20 Episode results for "Nicotinamide"

NAD+, Nicotinamide Riboside, and Nicotinamide Mononucleotide with Rhonda Patrick

FoundMyFitness

35:41 min | 1 year ago

NAD+, Nicotinamide Riboside, and Nicotinamide Mononucleotide with Rhonda Patrick

"Howdy folks today is a special episode rather than giving you an interview in this episode? I'd like to take a shot at instead giving you guys. The full lay of the land on a topic. We've continually touched on across multiple episodes. which is all things? And we've brushed up against this topic in many interviews. The most obvious obvious of which being the conversation I had with Dr David Sinclair but also others like prior episode with Dr Eric Burdon both great episodes which you should definitely listen to those episodes were however conversations which means that in each case while certainly educational they weren't necessarily structure to strictly strictly be a primer. Today's episode is different instead. My goal in this one is to structure it in a way as to give you an overview that can lay the framework towards your understanding channing the relevance the questions that still need to be answered by the field and also just my sort of concluding thoughts when it's all said and done not only on a d. she but also on the so called an boosters which are the NASD precursors nicotinamide right beside nicotine Ahmad Mina nuclear tied before we kicked offer a quick mention about this episode. It's actually been out for almost an entire week. Surprised you shouldn't be. This is one of the new elements of the engine that keeps foundmyfitness witness not only running but thriving by offering a few solid concrete perks for supporting memories. I am able to keep his podcast. Free Grow My team and actually make free foundmyfitness better than ever before premium members. Now get a pretty sweet list of benefits including a members. Only early access feed that also gives periodic. Eric exclusive content free updates on genetic reports when they come out twice per month a members only email summary of some of the most interesting research. That jumped out at me. This next one is a big one for audio only listeners. A powerpoint presentation with all the videos on screen graphics get the benefits of the video without the video. Take AAC my last podcast with Dr David Sinclair for example one hundred and fifty slides one hundred and fifty. Can you believe that. You also get a foundmyfitness t-shirt cert- fulfilled automatically by our print on demand distributor and. Finally this one's huge each month you get access to submit questions for my monthly members. Only question question and answer session. Every month. It's happening really and all of that is now available in one centralized members only page right on. My website called the members dashboard. This is your Mecca for all things premium. Are you ready to learn more. Avail yourself of the whole story behind the new premium offering the how what and Y.. Or just get signed up for fifteen dollars per month by heading over to foundmyfitness.com forward slash premium that's foundmyfitness dot com forward. Flash P R E M I U am premium. Really folks. This is so much better than at and it affords me the opportunity to continue making foundmyfitness fitness into the best mostly free resource that it can be without further ado onto the podcast today. I'm going to talk about a molecule that has become in recent eight years extremely relevant to the field of aging specifically. I'm referring to any D. plus which I will refer to. As N de for short and some of the related precursor molecules kills Nicotinamide riboside often referred to as an R. and nicotinamide mononucleosis tired often referred to as an these two precursor sir molecules are called an boosters which can both be found as consumer available supplements. Just in case. You've never heard of any. It's probably one of the most important molecules accuweather on the planet so important in fact that without it life would cease to exist to NATO boosters nicotinamide said nicotinamide mono nuclear tied at very high doses. This is an animal. Studies have both been shown to improve the way multiple tissues and cell types age including skeletal and heart muscle brain and stem cells. There have also I've been to preliminary clinical trials in humans showing nicotinamide riboside may raise energy levels in white blood cells. which is pretty darn cool however I still? I think there are many open questions that need to be answered regarding. Ad Boosters and I will touch on some of these concerns in this episode but the possibility that intracellular NASD may be increased from a supplement or several types of supplements is awfully interesting if not downright exciting for one. Simple reason energy levels decrease with age and a decrease in energy eighty levels across a variety of types of tissues is associated with many and naming many hallmarks of aging these hallmarks of aging that are associated with age related plated changes in the pool either directly or indirectly include things. Like loss of Proto. Stasis Might conroe Dysfunction Glucose Intolerance Insulin Insulin Resistance Cellular senescence altered epigenetics and more this is partly because the availability of promotes. DNA repair capacity while its decline is associated associated with the accumulation of DNA damaging reactive oxygen species another reason is because Nada's required for energy production so when energy levels decline as they do with age this results in less energy production in many tissues like the brain immune cells muscle etc.. That means those organs do not work as well as they once insted. During youth. When energy levels were maintained? Any ideas also required for the activation of a very important family of enzymes involved in longevity called Sir Tunes and the complete answer to why energy levels fall with age is still an open question. But there's a few things we do know. As we age chronic inflammation and immune activation two processes that consume NASD tend to go up and with them our need for DNA repair placing an immense demand on our energy pool. Meanwhile while our ability to produce and recycle tends to fall with age we're GONNA cover a lot of ground in this episode but I wanNA start with an overview of any D- Any any deal has a very important role in energy metabolism and can be synthesized in the body from a variety of dietary sources including the amino acid trip to fan which which is in tons of healthy foods like salmon spinach and nuts and the three forms of niacin which is vitamin B.. Three also found in foods like lean meats legumes veggies edges these three forms of vitamin B.. Three include nicotinamide also called Niacin nicotinic acid and nicotinamide riboside they are commonly referred to as Nice in equivalents but dietary sources of energy are not the major source of any D. The major source of energy is through a recycling mechanism that we will discuss later. The reason for that is because our organs require such large quantities of that it would be impossible to consume enough from our diet. So why why do we require such large quantities of any first and foremost energy plays a critical role in energy metabolism critical. Meaning without it. You can't make energy entity participates in back and forth processes of reduction and oxidation often referred to as Reebok's reactions these alternating conversions of NFC's oxidized form which Canady to its reduced form. An Age are crucial for the metabolism of glucose and fatty acids and the formation of ATP. Since both the oxidized is in reduced forms of amd are essential for these linked sets of reactions cells need to maintain massive concentrations of both and a D. and an age basically without these molecules. Not only would we cease to exist but life on our planet would cease to exist and it is also a cofactor for many different important enzymes in this context a cofactor means something that is required for an enzyme to work at has to bind to the enzyme and this activates the enzyme so it can performance function so. Let's talk about a few of these enzymes. Several these NATO required enzymes are inside the Mitochondria and this is another way and participates in the generation of energy aside from itself being a type of energetic currency it also acts as a cofactor for enzymes involved in the production of energy from glucose outside of the minor Qendra this is referred or to as glycolysis many types of cells us look like Hollis's as their primary source of energy. For example. Red Blood cells do not have any medical Andrea so one hundred percent of the energy. They require to perform their function of delivering oxygen and other goodies to other tissues in the body comes from glycolysis and plays a very important role in mitigating DNA. A damage you need repair damage to DNA. That is because any cofactor for one of the most important enzymes involved. In repairing DNA damage called part one the activation of part one requires an enormous amount of any D for example excessive DNA damage in subsequent one activation have been shown to decrease energy levels to twenty to thirty percent of its normal levels. The ability to repair DNA damage is important for longevity. LYMPHOBLASTIC cell lines established from blood samples of humans who were centenarians. One hundred years or older have significantly higher part one activity than cell lines established from younger individuals. That are seventy years old part. One activity has also been correlated with maximum lifespan. In mammals the higher the part one activity the longer lifespan. For example the activity of part one one was measured across multiple Mammalian species and the difference in powerpoint activity between the longest lived mammals tested which were humans and the shortest lived mammals tested. which were rats? It's was fivefold so not too much of a surprise but genomic stability which relies on energy in general and pop ones specifically maybe very important morton longevity is required to activate signaling proteins knowns or two which are highly conserved enzymes play roles in health span and longevity in multiple organisms uh-huh so to ends are linked to the regulation of variety of metabolic processes like the response to stress and the modulation of lifespan. The way they do this is through EPA genetic regulation so twins utilize ad to remove specific chemical structures called seal groups. A process called Elation from cellular proteins to control all the activation of genes involved in energy metabolism a toffee circadian rhythm DNA repair self-survival and more when sailor energy levels are low. Oh such as during exercising fasting or calorie restriction energy levels rise which also means the ratio of any to its reduced form and Adhd increases and. This serves as a sensor to switch on to an expression in subsequent activity repair. trawl a naturally occurring compound found in red grapes. Apes and other plants is a potent to inactivating compound and it's beneficial effects on health span. Some of which is now showing up in human research are thought to result from from Sir to inactivation. All right so that is an in a nutshell. It's important stuff. Unfortunately entity becomes depleted across various tissues including the brain as we age the brain skeletal muscle the heart. These are all tissues with a very high metabolic demand and thus require a lot of any D.. So what happens happens when you can't meet that metabolic demand things start to degenerate and fall apart. They don't work as well as I mentioned before. An eighty depletion has been associated with the hallmarks except aging such as decrease a toffee increased. DNA damage increased mighty contrel dysfunction and disrupt metabolism depletion of NATO may predispose organisms to the development of a variety of age related diseases including neurodegenerative disease such as Alzheimer's Disease and Parkinson's disease cardiovascular disease and muscle atrophy trophy. It may also increase the stability to infections since the immune system requires tons of EDNA entity in contrast energy levels increase under under conditions. That many of us already think of as generally health span promoting such as exercise and also fasting or in the case of lab rats full-blown lifelong lifelong caloric restriction. Furthermore and Eddie Restoration through a variety of different methods has been shown to increase lifespan in lower level organisms such as yeast east worms as well as in rodents taken together. These findings suggest any D- plays a critical role in aging specifically the reduction of energy levels levels commonly observed an aging is thought to be a combination of decreased synthesis and recycling as well as increased consumption and degradation increasing damage damage and inflammation as seen in aging may decrease in potentially aging. So the question. That's been on everyone's mind is can. IRA's energy levels in my body and if so so that gives me superpowers or at the very least helped me to live healthier and free of disease longer. The answer isn't just climent though. That's a possibility and one some labs are. I'm very excited about. In pursuing in fact energy levels are heavily influenced by lifestyle and particularly things that cause energy stress like fasting caloric restriction and an exercise which all raise ad remember any D can be made from things in the Diet like trip to fan or niacin equivalents. But these niacin equivalents Are not the major source of. NASD the reason for that is because the body's demand for an ad exceeds its capacity to produce it from these forms of vitamin B. Three so the body recycles nicotinamide using a recycling pathway called the NASD salvage. Pathway this is the predominant source of any D- Let let me explain how we get any D from this recycling pathway the consumption of energy from enzymes that use it generates nicotinamide as a byproduct nicotinamide is converted into Nicotinamide Mono nucleotides and subsequently into NASD. There are two important things to know about the salvage. Pathway First East nicotinamide has been shown to inhibit the activity of Sir two inns which is not necessarily a good thing second. The enzyme that converts nicotinamide into nicotinamide mononucleosis tide is subject to feedback inhibition by an eighty levels that means at a certain concentration of NASD nicotinamide will no longer be converted into Nicotinamide Mono nucleotides and subsequently rather it will remain nicotinamide. which which is unfortunate? Because as I just mentioned some studies have shown nicotinamide inhibits Sir to inactivation. Remember Sir tunes are involved in longevity that that means you want them to be activated the other source of energy is from nicotinamide riboside which is converted into nicotinamide mono- nuclear tied and subsequently eighty eighty both nicotinamide right beside nicotinamide mono- nuclear tied are found in low concentrations in many foods but they are also found in supplements and are referred to to as NASD boosters. So let's talk a D boosters. These two eighty precursors nicotinamide riboside nicotinamide mono nuclear tired are referred to as entity booster's because in supplement form. They have been shown to be well. Tolerated at high doses to effectively raise energy levels and to ameliorate age associated diseases in rodents. It's the most extensively studied any booster nicotinamide right beside several animal. Studies have shown that when Nicotinamide riboside is orally administered at high doses. Is it can counteract in obese. Genyk Diet improving insulin sensitivity. It can improve endurance and strength. Another animal studies showed at high dose nicotinamide. My Riverside could reverse mitochondrial damage. It could increase mitochondrial biogenesis and reverse muscular atrophy and animals that had a severe muscle wasting disease nicotinamide nicotinamide reiver's had has also been shown to have positive effects on the brain in animals. It increases neurogenesis. It's decreased cognitive deterioration and amyloid Beta production. It's also been shown to increase synoptic plasticity in mice nicotinamide Mono nucleotides has not been studied as extensively as nicotinamide riboside. But there have been several animal studies that have also shown nicotinamide mononucleosis I. It can have health benefits for example injection with high dose nicotinamide monitor. Nuclear tied has been shown to counter counter an obese agenda Diet and improved several markers of metabolic health high dose injection of nicotinamide minor. Nuclear tied has been shown to improve heart function in animals with heart problems problems and to improve cognition memory in animals with neurodegenerative disease. A long-term study found that Dietary Administration of Nicotinamide Modern tied mitigated the age associated physiological decline in mice that have an accelerated aging phenotype specifically starting at five months of age. Mice were fed either either a hundred or three hundred milligrams per kilogram body weight nicotinamide modern tied for twelve months. These animals had improve. Skeletal Muscle Function Mighty conroe function. Increased energy expenditure increased bone density and also decreased insulin resistance. These benefits occurred in a dose dependent manner so the higher the dose of Nicotinamide Monitor nuclear tied the greater the benefit. While this all sounds great. There's another important point that I want to mention. While many animal studies have found that nicotinamide riboside and nicotinamide nicotinamide mononucleosis tied can ameliorate age related disease by increasing energy levels in different tissues. There is always one disease context that throws a curveball cancer sir in a recent study nicotinamide mono nuclear tied was shown to accelerate cancer growth in mice with the type of pancreatic cancer where pro inflammatory senescence cells. It drive tumor growth when mice were injected with five hundred milligrams per kilogram body weight of nicotinamide. Monica tied. For thirteen days. They exhibited significant -nificant increases in precancerous and cancerous. Lesions in the pancreas. So let's talk about this. A little more. Because nicotinamide monitor nuclear tides effect on accelerating accelerating tumor growth was dependent on essence cells which can disrupt normal tissue functions and ironically also drive the progression of cancer over time. I'm as well. This is in spite of the fact that Senescence is a program that usually prevents cancer more immediately in the short term. The reason this happens. Is that when cells Dell's become senescent they can secrete molecules tend to have the following qualities. They are pro inflammatory. They're involved immune activation and evading eating the immune system they're involved in growth signaling and also involved in angiogenesis which plays a role in cancer metastasis. An seems to increase this quality of senescent cells likely because it's being used in terms of energy metabolism. So it's making these cells even these. Senescence sells even more tumor Schumer genetic and while this study only looked at nicotinamide mononucleosis effect on cancer growth. It's quite possible that nicotinamide riboside may show similar results in this very very very specific context which is a type of cancer. where pro inflammatory senescent cells drive tumor growth? That does not mean that nicotinamide mononucleosis nuclear tied or nicotinamide rive side. Supplementation will cause cancer or even drive tumor progression and other types of cancer. But I will say it would be nice nice to see long term animal studies to confirm. I'm sure those are underway. Now let's focus our attention on whether translation of all this preclinical data to humans is likely with the exception of the cancer study. I just mentioned much of the pre clinical data seems pretty promising but there are a couple of important points to make with respect to these. These animal studies that are very relevant for translating this data to humans first. Let's talk about dose and majority of the road in studies which use nicotinamide riboside orally. Ali used a very high dose of nicotinamide right beside in the range of four hundred milligrams per kilogram body weight which translates to a human equivalent. Dose a thirty two milligrams per kilogram body weight so for one hundred eighty pound person that would be approximately two point six grams of nicotinamide riboside per day. We will discuss human studies in a minute but that is a very high dose and it is a dose as orders of magnitude higher fire that has ever been clinically tested regarding the nicotinamide. Mononucleosis animal studies the majority of them. All used very high dose about five hundred third milligrams per kilogram body weight and typically. It was injected into the abdominal region of animals. Which makes it quite difficult to translate findings to humans? The oil does that was used in the long term aging study used a dose range on the low end the dose was one hundred milligrams per kilogram body weight which is a human human equivalent dose of around eight milligrams per kilogram body weight so for a hundred eighty pound person that translates to about six hundred fifty the three milligrams of nicotinamide mono nuclear tied. Which seems pretty doable? Of course the mitigation of age associated physiological decline was was much more robust at the high dose of three hundred milligrams per kilogram body weight. which is a human equivalent dose of twenty four milligrams per kilogram kilogram body weight or approximately two grams of nicotinamide Maher nuclear tied per day for one hundred eighty pound person again? That's a pretty high dose. The next point of concern is the bioavailability of either nicotinamide right beside or nicotinamide. Mononucleosis tied the important point. To address is whether nicotinamide all right beside or nicotinamide mono nucleoside can reach other tissues intact and directly form and a d. without going through that Nada recycling pathway. That I mentioned earlier called the salvage. Pathway the salvage pathway would mean that nicotinamide rives side or nicotinamide Mina. Nuclear tied ride were first metabolised into just nicotinamide before forming and a D. instead of directly forming any D this is an important point because NASD produced from the salvage. Pathway is subject to feedback inhibition and therefore cannot raise an eighty levels in tissues above love a certain level. So let's talk about some details. An animal study using isotope tracers allowed any D- made directly from nicotinamide arrive aside or directly from nicotinamide mono- nuclear tied versus NASD made from nicotinamide by the salvage pathway to be measured. What the study found was that I had a low oral dose of around fifty milligrams per kilogram body weight? If either nicotinamide right beside or nicotine Ahmad nicotinamide nicotinamide Mona nuclear tied. They produced very low levels of energy may directly from those precursors but only in the liver not another tissues low levels of nicotinamide. Dr N D on the other hand were found in the kidneys and very low levels of nicotinamide drive and Eddie were found in the muscles and also in the brain the human equivalent dose of fifty milligrams per kilogram body weight is roughly four point zero seven milligrams per kilogram body weight. Wait so for a hundred eighty pound person that is approximately three hundred thirty two milligrams of either nicotinamide riboside or nicotinamide. Tomorrow might WANNA nuclear. which is a pretty doable dose? But very little increases in NASD were found at least in animals at that dose. A higher oral dose was also done but only for nicotinamide right beside a dose of two hundred milligrams per kilogram body way of nicotinamide riboside. Aside showed no difference compared to a low dose in terms of making an direct from nicotinamide right beside in any other tissues other than the liver however however more of the NASD derived from the salvage. Pathway was found in the kidney muscle and the brain. They're not the lower dose so two hundred milligrams per kilogram kilogram body weight translates to around human equivalent. Dose of thirteen point six sorry sixteen point three milligrams per kilogram body weight. which for a hundred eighty? Any pound person is about one point three grams which is pretty high. When nicotinamide rival side or Nicotinamide Mon- nuclear tied were given intravenously at a bearing doses so fifty milligrams per kilogram body weight or five hundred milligrams per kilogram body weight directly produced an was found in the liver kidney and muscle in a dose dependent manner? However the only NASD detected in the brain was that which was salvaged from nicotinamide? Suggesting passing that neither nicotinamide right beside nor nicotinamide minor nuclear tied crossed the blood blood brain barrier it is not worthy that head to head comparison of identical doses of injected nicotinamide right beside and nicotinamide on a nuclear tied produced more and ad may directly from nicotinamide right beside aside in the liver kidney and particularly in the muscle tissue compared to nicotinamide monitoring tied. So what does this all mean and should we care what this data from the isotope. Tracer studies means is that even at very high oral doses neither nicotinamide riboside or or nicotinamide nucleotide appear to directly be transported to other tissues other than the liver at least again at those doses that were measured however however nicotinamide riboside and Nicotine Ahmad Maher nuclear tied were converted into nicotinamide which was then transported to other tissues and some of that nicotine in mind was then converted into an ad and at the end of the day isn't raising cellular energy levels. What is most important anyway? The other animal all studies previously mentioned that showed positive health benefits in tissues like the muscle or the brain. Were at a very high. Oral dose of Nicotinamide riboside and Nicotinamide in my modern nuclear tied. In fact in some cases they were doubled the dose so they were about four hundred milligrams per kilogram body weight. So it's possible possible that nicotinamide riboside and nicotinamide mono- nuclear tied can be transported to other tissues other than the liver at very very high oral doses is that that's yet to be shown however it's also possible that a very very high doses the derive from the salvage. Pathway was high enough to do something beneficial. The isotope the isotope data also suggests that if nicotinamide right beside or nicotinamide Mina nucleotides is administered intravenously. Both of those compounds are able to be transported to other tissues and directly form and a D. and not be subject to feedback doc inhibition. This also raises an eighty levels in multiple tissues to a much higher concentration than otherwise would be of course I be injection of these. Any boosters. Boosters is very challenging to translate to humans you may be wondering while the messing around with any d boosters like nicotinamide right beside nicotinamide nuclear tied in the first place the reason nicotinamide rives side and nicotinamide Ma. Nuclear tighter popular is because they can be transported into multiple tissue types including the liver kidney muscle and heart. The brain is the exception. Neither nicotinamide riverside nor nicotinamide mon.. A nuclear tides seemed to be able to directly cross the blood brain barrier but both form nicotinamide cinema which can be transported into all tissue types including the brain where it can then form an ad so why not just go to the source and take or inject an directly directly well for starters any has poor bioavailability animal. Studies have shown that upon ingestion oral orally administered any is primarily digested into the precursor nicotinamide but also to nicotinamide riverside and nicotinamide nucleotide before being absorbed while oral world biodegradability of energy is low. The hope is that intravenous infusion may bypass that digestive system. The problem is that no Mammalian in an eighty transporter has been identified and with the exception of the brain and the heart extra cellular. NASD has not been shown to be taken up into tissues when NATO was injected into the abdominal region of mice it was able to raise an ad levels in some brain regions similarly mice were injected with a high dose of NASD had increased crease levels of energy in the heart and also protection from cardiac hypertrophy this suggests that direct injection of NASD at high dose. Maybe doing something beneficial at least in the brain and heart. I would like to mention that. Just because no data exists that does not mean that any D- delivered Bert. intravenously cannot raise levels and other tissues other than the brain or the heart. It's possible that extra siler. AD could be metabolized nicotinamide and that could be transported to other tissues like muscle and also Be Converted into ad while there is very little little pre clinical Michael Data and zero clinical data on direct ivy injection of energy. It does seem like this may be also be a good idea or a good area to explore as a potential potential way to boost energy levels tissues. But let's move beyond what is plausible and talk about human data today. There is no published evidence of oral. nicotinamide Tim my Mono nucleotides supplementation humans but there have been two randomized placebo controlled trial showing that nicotinamide riboside can increase energy levels at least eastern white blood cells in a dose dependent manner. So let's talk about those in an eight week. Long randomized double blind placebo controlled study involving one hundred twenty healthy with the adults between the age of sixty and eighty years old a two hundred and fifty milligrams daily dose of Nicotinamide rive side and Tarot still being a natural compound on found in blueberries. That activates are two. In similar to resveratrol increased participants whole blood and a levels by forty percent compared to their baseline levels is just after four weeks participants whole blood. Any D levels increased by ninety percent when taking a double dose which was five hundred. Milligrams those who took the lower dose exhibited reduced diastolic blood pressure and lower levels of the liver enzyme Alan aminotransferase which is a marker of liver damage however is difficult to know whether nicotinamide riboside terro still being or both are responsible for the effects on blood pressure and liver. Health previous. Clinical studies have found that terror still being reduced blood pressure pressure at least an adult another randomized placebo controlled trial involving sixty middle aged and older adults between the ages of fifty five and seventy nine years old old demonstrated that a five hundred milligram. Dose of Nicotinamide right beside twice daily for a total of one gram per day for six weeks was well tolerated and increased. I energy levels in white blood cells by sixty percent. The study participants also experienced improvements in bloodpressure. A or stiffness but these effects were not statistically significant possibly due to the size of the dose or the relatively small number of people in the study nicotinamide riboside had no effect on metabolic function motor function or exercise capacity and performance. That's pretty much it. For the randomized placebo controlled trials. The data seems to indicate that oral nicotinamide hydride beside can raise energy levels and whole blood and in white blood cells but that it is only a conclude that's the only conclusion that can be made. The highest dose tested was one gram Rampart Day administered as five hundred milligrams twice a day if we circle back to the animal data on nicotinamide right beside and all the benefits that we're seeing that was was the human equivalent dose of thirty two milligrams per kilogram body weight which surround two point six grams per day. For one hundred eighty pound person while the short term clinical studies show nicotinamide antenna. My driver's side given orally is safe at least in the short term. No long term studies have been done. It's worth at least a small mention that nicotinamide riboside nicotinamide had mono nuclear tied both breakdown into nicotinamide over time. especially in conditions of high humidity or high heat somewhat perplexingly supplemental nicotinamide may even reduce adductor to inactivation. The good news is that overall if these supplements are kept hold their relatively stable and in most cases the supplements will contain very little nicotinamide. So it's a good idea to make sure that these products stay cool as much as possible and get them from a manufacturer to make sure that they have not been laying around in a hot warehouse house somewhere longer than necessary. Okay just to recap any is crucial for our survival. It can be obtained in the Diet but the body recycles it to get most of what it needs. Unfortunately Day to day living plus normal aging can cause any D levels to drop this causes metabolic micahel dysfunction as well as many of the other problems and conditions associated with aging like elevated DNA damage. Energy levels can go up when we exercise fast. But any boosters like nicotinamide my bribe aside and nicotinamide nucleotide can also an increased energy levels and dose dependent manner however most of the data on energy boosters comes from animal studies whether these boosters are effective and safe in humans is still a big question. So those are my thoughts on Ener D in a nutshell. I think the data on the precursors is very promising and exciting but out of abundance of caution much more needs to be done before. I'm ready to dive in with both feet. That's it for today's episode. Thank you so much for listening. If you would like to learn more about any D- nicotinamide riboside and nicotinamide mono nuclear tied check out the topic pages. My team and I put together remember earlier at the start of this podcast about my commitment to make foundmyfitness better than ever before this is one great example all now available on my website are deep dive overviews. We call topic pages if you have questions about anything you heard in. Today's podcast aside from asking me the question directly as a part of my monthly. QNA If you happen to be a premium member you can also just look them up on the topic pages and there's a really good chance. Your question might be answered right there. The topic pages are a free resource with illustrations dozens of citations and more literally. Everything we talked about today. I mean everything Sir Tunes. NASD nicotinamide riboside. nicotinamide mono- nuclear tied. Even the things we barely mentioned like resveratrol very troll have a topic page. This is a powerful new resource made available on my website to everyone mostly as a result of yes. You guessed it the support of my premium members. 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nicotinamide nicotinamide riboside NASD mononucleosis nicotinamide rive DNA damage Nicotinamide Modern niacin nicotinamide Mina NATO neurodegenerative disease nicotine Dr Eric Burdon nicotinamide riverside Dr David Sinclair Glucose Intolerance nicotinamide Ma
Episode 81: Charles Brenner discusses NR and the benefits of boosting NAD as we age

STEM-Talk

1:04:18 hr | 2 years ago

Episode 81: Charles Brenner discusses NR and the benefits of boosting NAD as we age

"Welcome to stem talk. Stem, talk stem talk. Welcome to stem, talk for introduce you to fascinating people who passionately inhabit the scientific and technical frontiers of our society. Hi, I'm your host, Don Cornelius joining me to introduce the days podcast as a man behind the curtain. Dr Ken Ford, agency's director, and chairman of the double secret selection committee, that sucks all the guests who appear in some talk done. Great to be here. Sorry guest. Today's Dr Charles Brenner. The ROY j Carver chair by chemistry at the university of Iowa. He's one of the world's leading experts on nicotinamide, Adnan dynamically tied commonly referred to as a D, which is actually an essential molecule found in every living cell in. Today's interview we talked to Charles about his research into NASD, and why he believes supplementation with nicotinamide riboside could help people age better. In addition to his work at the university of Iowa. His also the chief scientific adviser for Chroma dex, which markets are supplement true Nigen. But before we get to today's fessing meeting interview with Charles we. Have some housekeeping to take care of? I we really appreciate all of you who have subscribed to stem talk. And we are especially appreciative of all the wonderful five star reviews that have been piling up on ITN's these reviews really help us get the word out about the show. Thank you. Absolutely. And as we announced in several earlier episodes, the double secret sex and committee has been continually and carefully reviewing items giggle. Stitcher and other podcasts apps for the wittiest and most lavishly praised filled reviews to read on stem talk. As always if you hear your view read on some talk, just contact us at stem talk at H M, C dot US to claim your fficials stem. Talk t shirt today. Our winning review was posted by someone who goes by the moniker. Dr Wadi the review is titled inspiration for a wandering mind. It reads as a fourth year med student currently interviewing for residency positions. I've been on the road over the past month more than I've. Been home before my first road trip. I decided to give podcasts at try instead of my tire playlist of music in an attempt to make my driving time more productive. I was fortunate to have stumbled onto stem talk every episode has broadened my horizons in giving me potential jumping off points for future. Areas of research between Dr Kanagi in Dr Ford, the inciteful questions for guests are usually one step ahead of where I am which keeps me engaged on long trips. Well, thank you, Dr Wadi and thank you to over other listeners, help stem talk become such a great success. Okay. And now onto our interview with Dr Charles Brenner. Taught stem talk. Hi, welcome to stem talk. This is Don Connecticut's your host and joining us today. Dr Charles Brenner. Charles, welcome to the podcast. Thanks great to be here. And also joining us is Ken Ford Lou done and especially Hello, Charles, Charles. Is it true that you were a curious kid who dreamed of coming either a comedian or a rabbi? Yes, I think with those professions. Have in common is a love of words people happiness, and I would say healthy argument before I knew about being a scientist. You know, I saw comedians as rabbis and I had a little bit of the food for both. So in high school, you are on the tennis and cross country teams. But I understand it was the math team where you really stood out is that right? Yes. I I'll have to admit to being a math nerd in high school. Also did some theater wrote for the school newspaper, and I was active in the chew issue group as well and western Connecticut, so as a national merit scholar. You must have had a number of opportunities for college. So why did you decide on Westland? Well, I'm not sure how it works now. But at the time yet to specify where you would be a national merit scholar. If you were fortunate enough to be named a national merit scholar semifinalist, which which I was so when I got into Wesleyan and was named a national merit scholar. It was pretty much a done deal. Wesleyan was a terrific place for me to go to college. And so you showed up on campus, and he decided to major any college. But when you went to your adviser, you found out that Wesleyan didn't have an ecology department. So can you tell us what happened next year? Basically, I went to the doctor James Donna de the biology department. You know, that would have been the home of ecology if they had really had it. And of course, I didn't exactly know what ecology as an economic discipline. Was. But you know, I was someone that was interested in environmental science and environmental conservation. And you know, Dr Donny said, you know, it's not really something that we do a lot of here. So sensually what I did then which is what I've done many times in my life is made lemonade. Right. So he told me that we've got a great program here in molecular biology, and you know, trying to understand how life works at the molecular scale with DARA and proteins and dig in and find a research lab to participate in. So that's what I did. So after graduating with honors and biology, I understand that you traveled across country to work in the bay area. So what was that like, well, let's see it's nineteen eighty three. And I actually went to college with acquaint idea that you you go to school in order to not be a burden to your parents right to to learn some skills and be able to the employed, and it was really just early in the nineteen eighties that the biotechnology industry was. Being established in the San Francisco Bay area and in one twenty eight strip as it's called in the Boston area, and it was very attractive for me to go out west, and we didn't even call it. The biotech industry yet at the time. It was called the genetic engineering industry. But it was right around this time of year in nineteen eighty two. So the middle of by senior year that I went out and interviewed at a place called Chiron corporation, which was very small at the time and got a position there and started there in July nineteen eighty three was a great experience for me because I learned molecular biology, even you know, more than than in college. And also learned the value of teamwork because in industry, you can have fully formed. You know, scientists fully formed human beings that will work together in kind of larger groups in order to solve a common problem. And that's something that still is very appealing to me. After about five years you enrolled at Stanford. Erred and eventually earned a doctorate in cancer biology when and why did you become interested in cancer research? And also I understand that you are the first cancer biology graduate student in the biochemistry department is our way to second here. Can I'm not sure I like the sound of the word eventually. I Chris Ford half years in terms of cancer bio there were two of us actually viola Ellison, and I showed up in the offices of two new faculty members, Pat Brown and Bob fuller, respectively. Viola went to work on HIV. You know, molecular biology and I worked with Bob fuller, actually on pro hormone processing. But we were both even though she was doing molecular virology, and I was doing something that could be described as ends apology or molecular endocrinology because it related to hormone processing. We were the first to graduate students in cancer biology program that worked in in the BioChem department at at Stanford, another great environment, and like, my intellectual grandfather, Arthur Korn Berg was there on faculty and deal Kaiser, Bob Lehman, and I really have a number of mentors from from that period. It sounds terrific. So along the way. To get a whiff of an idea that everything was known about how nicotinamide Abney dynamically tighter. In a d was formed you worked on this from nineteen ninety six to two thousand three doing your time on faculty at Thomas Jefferson university. So can you tell us a little bit about that research actually got interested in all manner of nuclear tied binding protein, so the most famous nuclear tides are known by four letters AT GNC, right? And there's the a and the DNA version of those nuclear tides. They basically get built into our nation DNA, right? But there's all sorts of other small molecules in the cell that are considered a nuclear tides. So there's something called die identifying poly phosphates. There's the capped nucleotides that form the five prime ends of our an a, and and then there's any the central regulator of metabolism. And so I was working on a super family of enzymes that bind and interact with these unus-. Usual nucleus hides. And yes, it became clear to me that even though there was a lot of information on nuclear tides in biochemistry textbooks. And so that going back to Arthur Korn bergh's era in the late nineteen forties and nineteen fifties. That not everything was known about these molecules, including the synthesis of NA, d your research really took off it seems once she moved to Dartmouth in two thousand and three can you share with us how your work during this time lead to your discovery that and our or nicotinamide beside commonly referred to as an are is a precursor of any D. Could you talk a little bit about that? Well, let's start by stipulating that any D is the central regulator of metabolism. If you wanna understand how living things work, they're very few molecules of his great importance as a d so in two thousand three four around the time that I moved from Jefferson, Philip. Alfie to Dartmouth up in New Hampshire. I found myself working on an enzyme called gloomy dependent and desensitize. So this is an enzyme that. Maybe only ends Amal just would love. So it if you look at a diagram awaren- diagram of how yeast cells make any de and Ye star almost everyone's favourite model organism. They're a eukaryotic. Right. They they're used to make Prenton beer, but they're much more closely related to plants and animals than they are to 'Bacterial and all of the wiring for making a d- went through. This enzyme gloomy, independent any desensitize. So there was a pathway that was known to make any from trip to fan, the the amino acid, and there were EROs or pathways to make any d from two forms of vitamin B three, namely nicotinamide and nicotinic acid or or niacin all of those precursors trip to fan nicotine. Nicotinic acid had to go through the sense. I'm so what I realized is that I might be able to solve two problems. I might be able to figure out how the sense I'm works and elect joke that may be twelve people on earth would have been interested in that. And then in addition, I could test the received wisdom or the implicit assumptions that scientists were making when they drew those diagrams when they said that all routes to any d come from trip to fan nicotinic acid nicotinamide. So I wasn't sure that that was necessarily true. And I thought it was entirely possible that we would find a new way to make an another precursor or that we might find that one of the enzymes that was described as doing one thing could actually do two things, and it was in the course of doing that research that we really saw both problems. I we purified clue EMMY dependent any desensitize we figured out how it's two active sites work together. We saw those problems that the eleven other end zoologist were really. Interested in and then we cracked open the question of how in a d is made. And we showed that there's actually another pathway. So there's a pathway in eukaryotes from yeast all the way up to human beings that will take another vitamin precursor of any D N R, and then convert it into an AD the central regulator metabolism. So that involve discovering new genes, new enzymes, and then it wasn't just that discovery that turned out to be through or a number of previously unappreciated. Biochemical in genetic steps in forming a D N creating the NASD metabolism. And so as you said, I've been working on that problem really since about fifteen years now or around since two thousand three NADA's a coenzyme found in all living cells and it serves as a critical coenzyme for enzymes feel reduction oxidation reactions carrying electrons from one reaction to another. And as a coast substrate for other enzymes second, you get overview of research into NASD and Israel. Relationship to overall health and also age related disease. So I think I'd like to try to take this in three parts. I what is metabolism, and what is its relationship to this molecule that we call energy seconds. I want to introduce the concept of metabolic disruption or metabolic stress, and then third will tell you what is in our in. How does an are uniquely address these conditions of of metabolic stress. So you know, when when people think of metabolism, the first thing that that we tend to think about is our waistline. Right. So we tend to think well, if we're lean then we must have a fast metabolism. If we're gaining way. Maybe our metabolism is slowing down. But metabolism is quite a bit more than that metabolism is the process by which we convert our food into energy, but not only that actions thoughts and the function of every organ system, so the heart can't be muscle. Can't flex the lungs. Can't take. Oxygen neurons cannot transmit sensations or ideas without metabolic transformations. These are constant in every single cell and tissue and the central mediator of all of the chemical reactions that make up metabolism is a D or to be technically, correct. It's four related co-enzymes called any d plus n h an NA DP. Plus if you if you must entity so that these are coenzyme that convert one set of molecules to another so for example in cell division. A cell is going to need more nuclear tides to make more DNA Aren. A it can't do that. Without something called the Pentos phosphate pathway that depends on any D And ADP h making more plasma membrane making steroids like androgen and estrogens depends on any DP h converting our fuel into ATP depends on any. A d maintaining our blood glucose and Kitone bodies overnight depends on any Deitch. So these are the most important catalysts of cellular transformations that we have in our in our bodies. So that's metabolism. And and the relationship of any metabolism. The second important concept is what I call metabolic stress or metabolic disruption. So you would think that any D has gotta be like the family jewels or the crown jewel that would it would be protected against all invaders against, you know, all things that would attack the the organism, but it turns out that because any D coenzyme cz are required for resistance to a lot of toxic insults. The NASD system gets disrupted by metabolic stress, so examples of metabolic stress alcohol, isn't that funny? Right. 'cause we tend to think well we drink alcohol in order to distress ourselves. But. Actually in the processing of alcohol in our liver in the metabolism of alcohol in our liver. It affects her any D system when we made mice in our laboratory fat and type two diabetic it disrupted there any diesel stem in their liver when you expose skin or any other tissue to sun damage or oxygen damage reactive oxygen species. You're also depressing the NFC system when Anthony Salva in New York City, exposed mice to sufficient noise that it induced hearing loss it attacked there. Any D in the cochlea in the hearing organ in the ear timezone disruption jetlag affect the NASD system. And then in addition, there's disease processes, like heart failure and nearer to generation that affect the NASD system. So what I'm telling you is that any d is required for our metabolism. N? A D is disrupted by conditions of metabolic stress. And that you know, we need a de for all of our tissues to function. Right. So basically what I'm explaining to? You is that we need sources of what we call precursors in order to replete or to fill up our NFC stores, and what our research has done is at is put another molecule in the toolbox with the discovery of nicotinamide riboside with yet another way to fill our NADC stores, and what is unique. And this is the third and last thing that I'll tell you in this hopefully, not too long explanation that nicotinamide right beside has a number of properties that make it the most efficient molecule for filling R N E stores, and it turns out that under conditions of metabolic stress. Our ability to convert other precursors of NASD to any D goes into decline and the ability of a damaged or stress tissue to use an are actually goes up. So that's why there's quite a bit of value. Hugh in our and that's why our research, you know, is getting into not only common conditions of metabolic stress and an area that could be called healthy ageing. But also in its investigating the degree to which NR will be able to help in human diseases and conditions. Wow. That was quite a list of stresses that can diminish NA NASD when I was young which was long ago, and in the navy was common to experience nearly every one of those dresses those any defeats that you mentioned on a single trip or a a single day often. So one wonders what the effect was on all these young people. So so true about, you know, your time in the navy, but I'll go, and I'll talk to groups of people, and I'll ask for a show of hands of how many people would like to hop on a jet plane to Abe's fright, sit out in the sun and the fresh air you see where I'm going right listening to you know. Music could be at an elevated volume having some drinks and enjoying food up until the late hours, essentially, everyone will raise their hands. Right. And there you have alcohol over nutrition timezone disruption Sunday image, oxygen noise. And so a lot of these things are actually quite enjoyable if not inevitable stresses of life, and then you throw in some of the chronic conditions of aging and heart failure nerdy generation, and you see how potentially powerful and debating strategies can be for for health. Absolutely think about the guys in the current conflicts as special ops guys deploying to Afghanistan and wrapped they literally have every one of those tremendous noise stress, prodigious, alcohol consumption, jet lag. I mean, pretty much everyone. You just mentioned such aisles. I understand you're not a fan of the term anti-aging. In fact. From what I understand. He don't even use the term. So why is that? Well, I it sounds a little bit disrespectful like were opposed to maturity in agent. You know, all of us are trying to experience right second, it sort of conflicts, the kind of stuff that we're doing with nonscientific areas with, you know, snake oil were beauty treatments, or you know, anti-aging clinics. So no, I'm not really a fan. I do believe that because the NASD system is disrupted in so many conditions of metabolic stress that boosting or maintaining a D with nicotinamide Riva's side can help people age better. And for sure we're also very much involved in designing and participating in and reviewing clinical trials of nicotinamide Riva's side in in actual diseases and conditions. But you know, I don't love the term anti-aging. Yeah. It makes sense. The alternative to aging is not a pleasant very. Guinand Newt numerous other investigators have reported that any content declines with age following up on our discussion here and it seen him alterable organs from pancreas and adipose tissues guilt muscle liver, skin brain on. And I wonder do you have an apothecary. He's for why. In a d goes down over time. What is the current evidence in humans? Can you just give us a little primer on why any declines with age? Well, you know, in fact, a doctor Vernon's group in ours have a paper in review about this exact topic. And it's true that there are many experimental models in which people have observed tissue specific n de decline, and there are a number of theories, you know, one of the theories is that the expression of particular MD by synthetic genes or enzymes like nammed decline in aging or decline in conditions of metabolic stress, and there's evidence that. It's really true. So we have an example, it's not exactly age dependent. But it goes back to my theme of metabolic stress who went heart failure both in in mice as well. As in people, there's a decline in NASD, and there's lower expression of the enzyme that converts nicotinamide to any d- while there's increased expression of the nicotinamide Riva's side kind as two, gene. So that gene encodes an enzyme that allows the failing heart to use an R. And so the failing heart is losing the ability to use nicotinamide, and it's spiking up or increasing its ability to use nicotinamide rival in the course of its failure. So that's one theme that it's a change in the ability to use a vitamin A second possibility is that there's increased any deterrent over and these are not mutually exclusive possibilities. So you can have an. Crease in churn of NADA or turnover of any robbery of thievery as you call it earlier of any d- while there's also challenges to replenishing the NASD. So this is an area where I find myself having a little bit of a debate with some of the people in the field, some of the people in the field seem to think that it's a purely age dependent phenomenon and I'm inclined to think that it may be episodic. So the way that I would explain that to you is that if you would take photographs of a cat owners hands, you would see potentially evidence of increased scratches with time, right? So if you saw a set of photographs that were taken when that cat owner was forty fifty sixty years old, you might see more scratches on the hands in the picture from when the person would sixty you might be able to order those photographs. But I would contend to you that those scratches were not caused by time the scratches were caused by cats, and so it may be that the decline in NASD is more episodic and relates to conditions of metabolic stress that could include infection or microbiome and other kinds of episodes that we go through. And so this is really a very active area of research. But one of the great things about it is that the two technologies that my group has kind of developed can be applied to find out the diseases and conditions that could potentially benefit from an are. So one of our technologies is called targeted any D matab Aloma six so you folks know, what OMB IX names, right like Gino mix and transcript mix where rather than sequencing one, gene. Or looking at the expression of one are a you try to look at the whole complement of genes or aren't. So metabolism ex you measure, lots of metabolites at once and in quantitative targeted metabol-, you measure their absolute level. So we developed a sec -nology. And this technology tells us the conditions in which any D or maybe any DP h is under attack and then simultaneously. We can look at a targeted transcription analysis, and we can see whether some of the genes that were interested in are being induced, and I'll tell you Don and Ken when we see a condition in which either entity or any DP h is going down and nicotinamide right beside kindness. Gene is going up. That's a condition that has a very good chance of being addressed by NR. So those conditions include things like, you know, heart failure and nerd generation fatty liver and conditions like that. And that's that's what's really guiding our research into twenty nineteen that's a great a great with explaining nicotinamide. Add name dynamically tied phosphate. Which will from here on vertu entity. P H is particularly important because of its role as the central regulator of reactive oxygen species, Texas ity, so can you discuss this and DP h is really one of my favorite compounds. It's something that we don't talk about enough. So I'm glad that you're asking about it. So when we oxidized fuels were trying to take our lunch and turn it into ATP and carbon dioxide in large part. It's a little more complicated than that than that. But that's one of the ways to think about it. But one of the things about biology is that biology doesn't let the electrons go up in smoke. And so any age is carries electrons from our lunch and puts the electrons into what's called the electron transport chain, and that's used to generate ATP, but the other electron acceptors NAACP, and that generates has you said, Don and ADP H and the electrons and any ph are used to. Due to kinds of things one. They're used to detach FAI reactive oxygen species and to they're used to generate lipids, including estrogens, Andrew Johns, so reactive oxygen species. You know is a main kind of damage, in fact, it's a type of damage that is associated with aging. Now, the funny thing is that we know that reactive oxygen species is one of the mechanisms that will kill model organisms like worms so people thought. Well, great. So I'll put antioxidants on worms, and maybe I can extend their lifespan. But what people commonly find if you put antioxidants on worms. They actually live shorter life-span why because you need a certain amount of reactive oxygen stress in order to induce a response to reactive oxygen species that allows your body to kind of fight it. And so that's why. Antioxidants. Although, you know, there's some antioxidants that are in skin products for these kind of the outside of ru skin that may have some value antioxidants as medicine have kind of failed. What NR does on the other hand is by boosting any DP age. It boosts your natural antioxidant defense. So that when reactive oxygen species are generated we can detach affi- them in the cells that need that detects vacation in. In addition. We can maintain our bio synthetic capacity to make very important compounds like estrogen and androgen so entity P H is really important. We find that when we overfeed a mouse and ADP h is the most sensitive metabolite declines more than any diplomas. And we're quite certain that by Repleting or filling up the stores of any DP h in the liver where protecting whole-body metabolism. Stem talk is an educational service of the Florida institute for human machine condition. A not for profit research lab pioneering groundbreaking technologies aimed at leveraging and extending human cognition perception, locomotion and resilience. So if you years ago your lab, it's a mouse studies that looked at abusively type two diabetes. Can you talk about those experiments and findings yet we decided it was actually a first mouse experiment. We decided to make mice fat and type two diabetic with a high fat diet, and in the course of doing that these mice in just, you know, two three months time got a whole host of metabolic dysregulation. So they got a fatty liver. They started circulating high levels of liver. Enzymes like Allie aminotransferase aspartame being transfers. They had elevated blood glucose fasting and non fasting blood glucose, and they started developing diabetic Polly neuropathy pre diabetic Paulina Rathi, then when we push them into type two diabetes. Got a full blown diabetic nerve damage. If we gave them nicotinamide Riva's side, we could blunt the weight gain we could partially contain the fatty liver. We could lower the circulating. Liver. Enzymes lower their blood glucose and largely prevent the diabetic nerve damage. It was amazing now it would be truly amazing if he could do that in a human being, but the problem is that human obesity, common, human, obesity and type two diabetes don't develop you know, over two three months in a human being they develop over two or three or four decades. Right. It's decades of over nutrition. It's decades of an imbalance between our energy intake, the amount of food that we're eating and our energy expenditure. How much where you know? How many calories were burning over the course of the day to to our physical activity, whereas we've already completed human safety studies in overweight men to show that you know, even two grams of nicotinamide rival side is safe in overweight people it's gonna take a longer trial than twelve weeks in order to be able to move the needle on. Some of these parameters, but the evidence from the published human clinical study indicates that of all of the things that I mentioned, namely, the fatty liver. The blood glucose, the circulating, liver enzymes and the diabetic neuropathy, probably the most sensitive parameter in a human being is going to be fatty liver. And so we what we think will be able to do is by randomize ING people for a paddock status for fatty liver and giving them nicotinamide Riva's side for probably a six months at a at an elevated dose. We think that there's a very good chance that will we will be able to put a dent in a human fatty liver disease with this safe over the counter of item, it now one thing, I should definitely tell listeners is that I have an IP interest in this technology. So as you both know when I was on the faculty at Dartmouth, and we discovered the yeast and human nicotinamide reside side kindness pathway, and we discuss. Covered the phenomenon that nicotinamide riboside could be in fact, a human be three a human any D precursor vitamin we filed for and were granted intellectual property for the uses of nicotinamide riboside, and that's been exclusively licensed by Chroma decks corporation for which I serve as the chief scientific adviser. So I'm a I've an IP interest in and are, and I advise the company that developed it and I received grants from from this company but going forward we're really committed to doing the safe testing of an are. So that it's not only available to people just as a wellness product, which it is now has true Naijun. But in addition that it could be indicated for people that have an authentic disease or condition and has so I suspect a lot of our listeners after listening to previous answers and some of the discussion they're wondering, how do I learn if my NADA or energy levels are distributed. Is there an easy way to do this? Well, it's a good question. There's an easy way for my lab to determine people's blood and a D, but their blood in D is really not all of that interesting or actionable we've seen very few human diseases or conditions in which people are walking around with low blood AD, so depressed tissue in is probably, you know, much more common. But, you know, even in people that have a failing heart and low cardiac, and it doesn't mean necessarily that they're going to be walking around with low blood NA. So although I have the technology in my laboratory, I could really commercialize this at any time in order to measure people's blood, and I don't really see it as a terribly useful readout for most consumers that said we have discovered some of very interesting biomarkers that when you. You elevate people's NASD in as little as three weeks of time. There are some things that you can see in their blood that improve. I'm not ready to tell the podcast listeners, what those factors are because this work is in peer review, and it will upset the peer reviewers if I just blurted out before the reviewers have a have a chance to review all of the data. But we have identified some companion biomarkers that go along with boosting people's N E safely with nicotinamide Ribes side, and it will be very straightforward for people to to measure measure, those can you talk about the Acadian rhythms of any Di I've read that there's a diurnal cycle of AD essentially, a daytime peak and nighttime peek, and this would seem to imply to me a possible benefit to dosing in the morning and before bed does that make any sense or am I way off the beam on that? No know, that's pretty much my thinking as well. So it pretty much makes sense to for those people that are taking nicotine right beside to take a morning does. And if they decide to increase their dose to take it twice a day separated about twelve hours the work that we've done indicates that there is a diurnal function of the AD metabolism in the liver. It's not been investigated in every single tissue. But I think it's pretty likely that there are two peaks a day. And so if you're taking a morning dose, you are contributing most to your daytime and a cycle and a dinner time, those would be contributing most to your evening and disciple. So NR's phosphorylation to nicotinamide Monica time, which we will refer to an amend by nicotinamide Riva's side, kind as is and then m n is converted to any D. So as reported in two thousand sixteen saw metabolism paper mills, Al. Conducted a twelve month long administration of amend while tight mice which mitigated much of normal age related physiological decline, and so then administered mice switch their main energy source from glucose to fatty acids, and these results suggests that an amend has significant preventative effect against ages impairment and energy metabolism of mice. So Suming that the human trials are now underway demonstrate safety and efficacy. Why not supplement directly with an amend? This kind of amazing to me that this is still a debate in the scientific world. So in a man has a fos fate on it. It's a nuclear tied in a d has two phosphates and DP P H three phosphates compounds with phosphates don't get into cells. We've known that for fifty or sixty years. It would be great. If compounds with fos fates did get into cells because there's a lot of classes of drugs that essentially act as nuclear. Side. So there's anti retroviral drugs. There's anticancer drugs that compete with ATP or compete with nuclear tides and so forth, but you cannot deliver those compounds as nuclear tides, and when we another's have looked at an amend. We've clearly demonstrated that enema n- and Anna de both have to be Defosses for elated or converted to a vitamin in order to get into cells and to regenerate cellular AD. So people thought that they were being clever by using an amend because. Right. If we had a whiteboard here, I would show you that NR goes into cells and ours, then converted to end a man, and then amend is converted into NASD. And then some of the NFC goes to any P. So what people thought that they were doing with an amend is taking a shortcut, they're taking a compound that is closer to NASD than and our because it's already and are with the phosphate, but. Our research shows that that phosphate has to come off outside of cells. And then the fos- fate has to be put on inside of cells again. So I am impressed with the physiological effects of amend. So if you feed mice high-dose cinnamon, a lot of good things happen, it looks very much like feeding mice with high dose, and are, but no it doesn't really make sense to do the trials in mice or and people within amend because the end is not cellular -ly available in the the study that we're discussing the authors seem to say that in n appeared to mediates anti-aging effects, and we're talking mice at least in part by preventing aging associated, gene expression changes in a strongly tissue dependent manner. And does wondering Desa slightly different discussion. But you're the guy to talk to about this. So, you know, the authors talked about skeletal muscle as being one of the most sensitive target tissues for these anti-aging effects that. Associated with gene expression changes. Do you have any thoughts on that angle on this? Well, we have a study that's in a review right now that shows that Orel nicotinamide Riva's side, given to people had affect on their skeletal, muscle, gene expression. So we know that in our becomes available to people skeletal muscle. I'm not quite sure how much is known about in a man and the tissue specific effects of an are versus cinnamon Etta man is sort of a delivery molecule for an are because the phosphate has to come off. So it's possible that it gets to a different place or at a different speed than an are. But I would expect that they would largely function interchangeably, and that they would, you know, both depend upon conversion to an are outside of the cell, and then be taken up then. Yeah. When you're boosting AD inside of cells, you're going to do a lot of things. You're going to have the potential to improve DNA repair. Because DNA repair depends on any d you have the potential to improve estrogen and androgen, synthesis. You have the potential to improve resistance to reactive oxygen species stress and a lot of good things will happen. If you're restoring cellular energy now is good. Thank you. Some people are going the route of intravenous in a d infusions, but sense as far as I know cells can't take up any directly, these NASD IV clinics. That seemed to be springing up all over the country would appear to me to be unlikely to be effective that said, there is all kinds of antidoto reports of benefit could it be that some of the ideas. Converting to end our or in a m and having the benefit in that fashion. Probably an inefficient way to do it. If that were the case, what's your take on any D, IV infusions? Well, I've gone to. To a conference on I've E A D infusions. And I believe that in April be at another one. I would say that the anecdotal reports are pretty striking and a a little difficult to dismiss. But none of them have been evaluated against placebo controls, and I've actually gone to one of these conferences and proposed a crossover study in which people go from an oral nicotinamide rive aside, and and crossover to an IV people who are on IV crossover to oral some of the folks that are administering this type of IV a therapy. Are so convinced that it works, and that it helps people quit drugs that they don't consider it ethical to do the placebo control. I I don't agree with that. I think that the way that we're going to change medicine and change healthcare practices is by following the rules. And to placebo controls. But the way that we can make sure that everyone is getting the benefit of either Orel and our or intravenous in a dis to do a crossover in which everybody gets essentially both treatments either. You know, I the IV or I the oral and are and then and then does does the crossover. The other thing that I'll tell you in. This is these are data that I showed at such a conference is that in a collaboration with a group in Paris. It was Eric to plu two UP L U S, and the first author was Vour V A U R A, we showed that in a model of central brain injury. That's caused by high dose an MDA so excited toxic brain injury that nicotinamide Rives side was more effective than any NASD. So any D worked at something? Either. Oh, it was fifteen times higher concentration than nicotinamide Rives side at reducing the size of this brain lesion, and the reason that it took so much any D as exactly as you suggested Ken that the NASD has to be degraded back to an are in order to go into these cells and to restore the the energy and restore brain function. So we think that it entirely possible that there will be a better way to formulate and or deliver nicotinamide Rivasi's. But I don't think it's going to be an idiot self now when we eat food, right? If you eat whole food with a small w in a small f-, I'm not making a store endorsement. But when you eat a cellular stuff, you're getting lots of any NASD getting lots of any D And D H E P H and to a lesser degree and ADP. So our bodies have the ability to digest an coenzyme down to the vitamins, and then ourselves take up those vitamins. Now, the reason that we don't just go out and eat more AD or eat more food is that over nutrition itself attacks, the NASD system in our liver as we've shown from work with mice. And in addition because we can't control our microbiome. We can't control the digestive path that the NASD will take. So we don't know how much of the NASD that we eat is going to be available. As are available as nicotinamide were available as nicotinic acid in terms of. And that's just on the route from any being degraded down to two something without a fos fate, and that just doesn't get taken up on its own Earl. Earlier we discussed increased production of any d through supplementation with the precursor specifically in our another way to skin the cat might be any despairing through the Kitone metabolism. Many of our listeners consume various versions of the kid jank diet or intermittent fasting or time restricted eating in which they find themselves in Cuba. Jenex state in recent twenty eight teen paper it was reported that key tones can increase the reeboks in D plus in the h ratio in the brain of healthy adults. And so I I wondered if some of the beneficial effect that one sees in time restricted eating or Kita genyk diets might really be down to any D. Another words, I wonder if the increased in a d as result of the cute Olympic Tabalanza might be one of the primary mechanism behind the beneficial effects of these diets in a variety of brain disorders, and in promoting health and lunge. Avidity? Have you given that any thought I've given it a little bit of thought and we've done some some ashtrays in that space. I don't think that any d is going to be the whole story in the ketogenic diet for sure within the change the fuel source from you know, a balanced diet to very high fat, low carbohydrate diet, you are for sure, you know, changing patterns of of any D reduction in oxygen, and there may be something to that. We also think that there's a relationship between time restricted feeding and any disciples between liver, hyper set election and over nutrition and so forth, and that's definitely an area. Further research. Never certainly an interesting paper. And I think a can't explain all the effects that you see from the diet are other means of attaining decay Degen estate, but it might be that any Dee is playing an important role in there. So. Recently, the university of Colorado announced the results of a human trial that found Nigen increase in D. Plus by sixty percent in healthy middle age and older adults after just six weeks, can you give us an overview of that human trial to this was a trial that was done at university of Colorado, and they were there healthy older adults. The first thing that they wanted to assess with safety, right? So they're giving I think it was a gram of nicotinamide Riva's side per day to older men and women. These people were lean and in good health and one of the unexpected. But to light Foale outcomes was that nearly half of the participants had moderately elevated blood pressure in the group that had moderately elevated blood pressure. Who's a strong tendency of taking an are to lower their blood pressure and to improve their vascular function as measured by arterial stiffness. And so this was the first indication not only of the. Safety of chronic use of nicotinamide riboside, but the potential efficacy in improving human cardiovascular health until there's larger trials that have been designed that are being conducted. Right now says it possible that taking high doses of a b three deplete methyl groups. That's something that you can draw on an envelope. Right. So you can say let's see you put in more nicotinamide nicotinic acid award nicotinamide Riva's side, you're going to boost NA NASD, and in the course of all of any D metabolism. There's gonna be a methyl group added to nicotinamide in we've shown that people excrete in in our urine, methyl nicotinamide and and related metabolites. There's been some questions about that. We've already looked at that as a function of dose of nicotinamide right beside and at one hundred milligrams three hundred milligrams at a at a gram a day. We've not seen any depression in one carbon metabolism and methyl group metabolism. So if there were. Were a depletion of methyl groups than you would see elevated homocysteine and depressed as done seal methionine, and we've looked for that. And we've not seen it. So that paper is been written and is going into peer review, speaking of dosing. We earlier discussed a possible increased efficacy of twice a day. Dosing once in the morning once right before bed, perhaps what is the current evidence show as an optimal? If there is such a dose in humans is five hundred milligrams twice a day. What does it look like from your standpoint? Well, you know, one of the differences between me and some of the other people in in the field is I'm not gonna tell you what I take. I'm not gonna tell you what my dad is taking an am not gonna you know, I'm going to try to not dwell on anecdotal data the recommended dose. You know, that is on a bottle of true Naijun is three hundred mil. Grams per day, we initially had a product in which the recommended daily serving was to one hundred twenty five milligram capsules. But we found that since we've published clinical experiments at one hundred three hundred milligrams one gram that it made more sense for us to seek regulatory approval to go ahead and and recommend three hundred milligrams. Now, there's certainly people that take more, and we always tell people that if you have a disease or condition, you should ask your doctor. So, you know, you're you're getting out a little bit head of your skis. If you're self medicating for, you know, sciatica wore cuma therapeutic neuropathy or something like that anecdotally. There certainly are people that report benefits in general people that are looking for what would be termed therapeutic benefits are dosing either on the basis of their own experience or in consultation with their. Their physician at something on the order of Graham, you know, per day, you know, maybe four hundred fifty or six hundred milligrams in the in the morning, and you know, maybe three hundred to six hundred milligrams in the evening. This is really something that people should, you know, try to work out on their own, and in customization with a physician as it says on the bottle. You know, it's not intended to treat diagnose prevent a disease or condition. We've tested for safety. Right. And it's been tested to safety up to two grams per day, and we feel good about the fact that it does have a new dietary ingredient notification actually to such notifications from the US FDA and has a generally regarded as safe designate from the US FDA. There is no other nicotinamide Riva's side that you know, that carries those designations that means that the FDA would receive reports of adverse events, we don't know of adverse events they haven't come up in our clinical trials and the FDA. A drawers for this product are very clean. And so we feel good about that. But I'm not gonna make a specific recommendation of that would be optimal for one particular person. People come in different sizes and have different different needs to research reported in two thousand seventeen coming from Joshua Rabinowitz, his lab at Princeton challenged the long view that the mitochondria in a membrane is impermeable to purity nuclear tides and suggested the existence of an unrecognized mammalian in D or any D H transporter. So do you think there is a entity or NH transporter in humans? I think that it's pretty convincing at this point that they're two or three lines of reasoning that indicate the NASD that is made in the what I call the nucleoside a plasma the nucleus and the site. Applies him becomes available to the mitochondria compartment through specific transporter. We know of two or three groups that are looking for that transporter. I'm going to quote, an limb and predict that someone is going to present that molecule. By the time of the summer and a D conference in Dublin Ireland's this year, I think that that that is going to be discovered. Now be interesting the twenty teen Lou paper in cell metabolism. Also from Rabinowitz his lab seems to show that in mice oral in. Our is only converted to any d by the liver with no other tissues seen enough in our or presumably and amend to reach adequate side Asala like levels, thus in less. Increasing paddock entity provides benefit. This study would lead one to believe that oral ingestion of NR is of little value in the studies widely interpreted this way, I imagined. You may have some thoughts on this study that you could share with us. So it it essentially can't be true in the sense that there are three different studies that have shown that oral nicotinamide Riva's side. Acts in shoes outside of the liver. So extra hypnotic tissues. So I think I'm I've told do about two of them already one is in heart failure. So we have a heart failure model in which the ability of the failing heart to convert nicotinamide to an idea going down and the ability of the failing heart to convert an are two entities going up because there's a by winner jet a crisis in the heart. It costs less ATP to use NR's a precursor. We showed in that paper. It's by D, gay D, I G U E T at all in circulation that that's the name of the journal circulation. That nicotinamide does not restore cardiac in a d and that nicotinamide rival side does restore cardiac entity. So if all of the an R was being taken up by the liver and the liver. Was the street distributing nicotinamide than nicotinamide, and our would be the same in that model, and they're not and our works and nicotinamide doesn't similarly there's a paper from the Bauer group in Philadelphia in incidentally, Bauer was a co author with Rabinowitz that show that they knocked out skeletal muscle nicotinamide salvage and oral nicotinamide Rivasi's rescued the skeletal muscle deficiency in eighty so once again, if you knock out the ability of skeletal muscle to use nicotinamide and nicotinamide can't get past the liver than neither nicotinamide or an are should rescue that at mouse. But, but in fact, nicotinamide Riva's side rescues that mouse, and then third there are a number of experiments that show that there are tissues like a failing a nerve in which the nicotinamide regicide side kind. As pathway is induced. So it's there's a damn, you know, a damaged nerve induces, the anarchy one, gene. And or the enter K two gene in this Vour at all paper, we showed that in a damaged nerve anarchy one and anarchy to our transcription -ly induced and those genes wouldn't be coming up unless there's ability of nicotinamide rob side to be available to the brain and to to damage nerves. So one of the problems with nicotinamide Riva's side is that we can't extracted efficiently from blood when we draw blood. There's a cellular enzyme that spills out that degrades the an are there's a digital problems with extracting, and and quantifying, and are we can extract an entity p perfectly well from blood, but it's very hard to account for the NR. So we think that there are technical issues with the. Leo and Rabinowitz paper as elegant as it was and that it's not arguable that all of the at ours taken up by the liver because there are so many systems that show affects of and are that are beyond the liver in terms of additional human trials. Can you share with us what you're working on in the timeframe for when you think we might see some results from those trials? Okay. So let's start with there's one that we have in peer review right now that looked at the ability of nicotinamide Riva's side to be available to people's muscle. And we also found really I think pretty exciting useful biomarker of elevating people's NA de with oral nicotinamide reiver's site. So that should be coming out fairly soon. My colleague here at the university of Iowa, Dr Donna Hammond has a National Cancer Institute funded clinical trial on using our this is a small scale study. But to use an are to see if she can keep women on treatment who are being treated for metastatic breast cancer with cancer chemotherapy drugs that make people suffer from neuropathy. That's going to be something that I think. Launches in twenty nineteen. She's got an I n t application that has been approved that allows her to start that there is a mild cognitive impairment study that is being done in San Antonio at the Claude pepper center there. I know that it's been accruing patients for some time. Now, there's lots of studies I think that there's more than two dozen that have been registered around the world. And so, you know, every year there should be more clinical data on nicotinamide Ribes side. We always look at safety first and we look at measures of efficacy second. You know, the the thing is that people design the trials in a thoughtful way, you know, if you're looking at, you know, human obesity, you can't treat a human being as you know, is an oversize mouse, right mice get obese. City and type two diabetes and a couple of months humans get obesity type two diabetes over the course of decades. And so you have to design the trial to have, you know, a long enough period in which you can observe things, and you need to know, what are the driver biomarkers, and what are the passenger driver markers? So what's the thing that you're affecting? I if you guess wrong like someone in Denmark guest that nicotinamide Rives side was going to be rapidly, insulin, sensitizing and human beings or rapidly causing weight loss and human beings, and you randomize on the basis of weight loss or insulin sensitizing than you may not be able to detect a really meaningful effect on fatty liver. And so, you know, the the Danish study clearly looked like it was moving the needle on fatty liver, but we didn't have the men randomized for fatty liver. And so we were not able to get to P point. Surra five when that with that study. But we think that, you know, the studies are getting wiser, and there's a lot of investment that is being made in testing the efficacy of nicotinamide Rives side. And so we think that in twenty nineteen and twenty twenty year going to see some some important clinic clinical studies published really excited about following this studies and the results of the studies say certainly after all that have a lot on your plate right now. And I guess it's a good thing that back in college fell in love with the lab because to this day sounds like you still the lab at all suspend a lava time there, but I also that your fitness enthusiasts. If there's anything that can drag you the lab opportunity to do some high intensity interval training is that right? And second question on this is if so what does your training regimen? Look like see there, you go trying to get me to make you know for other people will exercise so important eating eating, right, right? You know, people ask me healthy aging all the time as though I? I would have you know, sort of different, you know, advice than what your mom or grandmother would would give you right? So the the first thing is to try to eat well and sleep well and get enough physical activity when I turned forty five I stopped using the elevator unless I really can't find it or terribly late for a meeting. I try to use the stairs. But high intensity exercise is is great. So I I'm in a group fitness class where you know, over the course of of an hour on a rowing machine a treadmill and using some free free weights. I really like being in a group class because a feel like I get pushed harder in the group class than I would necessarily work out on my own over the course of the past few years of also try to bunch of other things like Vigna, you know, yoga, and I like skiing and cycling metabol- swimmer. So I don't see myself to triathlon anytime soon. But I just enjoy working out hard and enjoyed dance and music and trying to stay positive that those are some of the the keys that I have to living better and trying to be productive and and happy in my life. Fantastic. Charles. Thank you so much for joining us today. Had a great discussion. And really have enjoyed having you on the podcast. My pleasure. Yes. It was. Great charles. Thank you for me too. Stem stem taught stem talk. Well, I can certainly understand. Why Charles became so fascinated with his research into any and are there's so many potential human uses of nicotinamide rival side. There doesn't seem to be a promise. But of course, a lot more research needs to be done as Charles mentioned in the interview will be fascinating to see the results of the upcoming and current human trials not yet published. Yes, absolutely forward to seeing the results of this trials to if you enjoyed this interview as much as we did we invite you to visit the stem talk patriot can find the show notes for this and other episodes stem, talk dot US, this is Dunkin signing off for now is Ken Ford. Saying goodbye until we need again on stem talk. Thank you for listening to stem talk. We want this podcast to be discovered by others. So please take a minute to go to ITN's to rate the podcast, and perhaps even ride review more information about this and other episodes can be found at our website stem, talk dot US there. You can also find more information about guests. We interview.

nicotinamide NASD Orel nicotinamide Riva fatty liver scientist Dr Ken Ford NADA Dr Charles Brenner Don Cornelius ITN Dartmouth university of Iowa Dr Wadi tennis Adnan Naijun NFC Don Connecticut Gene
Is Pterostilbene better than Resveratrol?

Limitless Mindset

22:55 min | 8 months ago

Is Pterostilbene better than Resveratrol?

"This is John Limitless mindset and in this podcast. We're going to be addressing. The question is patera still been better than resveratrol, so you are going to want to go and check out the article. Version of this podcast that is going to be linked Balu wherever you are listening to this as that article is going to have all the good stuff, it's GonNa have links to the science. It's GonNa have be linked to the sources of this stuff that I. Recommend and I will be updating that article in the future. You know sometimes i. come across new information. Sometimes I change my conclusions. Change my mind on things and these podcasts these. These multimedia formats where you can hear my voice. It's just a little bit more of intimate experience. These are unfortunately static media. They don't change until I. Record them and put something else out. Whereas the html format is oh, so dynamic so I do suggest that you go and check out my website limitless mindset dot com that is where all of the good stuff is at. So unsure you've had this experience. You are at a dinner or cocktail party, and you're drinking a glass of red wine, and then you encounter another another fellow traveller, drinking red wine, and you say hey smart guy or smart looking Gal. Di heard that white That red wine is healthy, and they will invariably respond. Yeah, yeah, I heard the same thing you know that's because of the read very tall right? I think that's something that having. That's a a health meme that has gone all the way around the world down I think almost everybody has heard that now, and this is because the red wine industry has done an amazing marketing job like Bravo, good job, red wine industry you just you know hats off to you guys on the rebranding of red wine as quote unquote healthy. Well I'm here to inform. Inform you that Sadly red wine isn't actually healthy, unless you're drinking really high quality, organic, biodynamic red wine, then it is arguably healthy and I do of course include a link to a source of. Good stuff I, I do I. Do have affiliate arrangement with one of the biodynamic red wine companies out. There I have not tried their stuff yet. I would love to hear that it tastes amazing, and you pay a pretty penny for that but I. do have a linked to that in the article if you WANNA try. Extensively healthy red wine. So red wine does include veritable, which is a well researched anti ageing compound that has a mechanism flipping the EPA genetic switches in our genome. As, much as I enjoy red wine from time to time, the lesser known compound Patera, still being has a more potent anti aging effect, though so I showed the two molecules. They are very similar molecules. Let's talk about the advantages of Patera. Still Buy. It is more bioavailable. It has improved life illicit. Over reservatrol which taken orally is just not that bioavailable, which is why you better you know, have that. Have those extra. Three or four glasses of red wine. Make sure you're getting enough of that RESVERATROL, okay? The potato by also has better bio. Activity is able to cross cell membranes better. and. It's more of a classic nutro pick. It has cognition and memory enhancing effects. And importantly this is the one that stands out to me. Potato still by doesn't blunt exercise gains. I don't take virtual because there's evidence from two human clinical trials that resveratrol hurts the gains that you might make in the gym particularly in Aerobic and cardiovascular exercise so. If you'RE GONNA go and hit the gym and feel real proud of yourself for your session kicking ass the gym you know, take a couple of cell fees. Upload those two instagram stories, and then go home and. Pound a couple glasses of red wine. That's that's not such a good idea. Nor is it a great idea to be taking resveratrol capsules on a regular basis? If you're a person that's working out in the gym and you're in otherwise good health. Okay, let's look at the scientific research. There are over five hundred scientific papers about Patera, still buying published and several clinical trials. A landmark randomized double blind placebo controlled two thousand seventeen. American study was published in the respected Journal. Nature and I include a nice diagram in the article from that study there in respected Jerrell nature on my article, so you're going to want to go and check. That here's some of the takeaways from that study, one hundred twenty elderly participants and add to use a statistically relevant amount of elderly citizens, and they were between the ages of sixty and eighty years old, and I'm trying to at this moment. Come up with a really great joke about. Old people trying to date like if you were an old codger, an old guy and you were a dirty old man trying to. Hook up with someone's grandma boy. This study would be quite a place to pull that off. Don't you think babe? Okay who cover some grandma. Yeah, you know. There's one hundred twenty elderly participants, so if you wanted to pick up a grant, granny like that would be the place to do it right Oh. Well, it's raining. was there rich Yay yet? Well, that's what I would be in the market for. If you wherever you know directed by. And I had no hope of ever returning I go I. Go for the rich granny. Really Oh. Yeah, yeah, for sure. Well the, Sexy, part, Dancing. Yeah Yeah. I'd probably do use the same move used on you. Which is you know? Teach him to dance, and then you know that would lead lead somewhere else. Really okay. Let's get back to the science. Though patera still bind was taken along alongside nicotinamide riboside, which is an entity plus precursor. which they called in our PT in the study, you know these scientists. They just love to refer to everything by an acronym. Everything must have an acronym and. PATERA still buying was an entity plus hack. The two together increase any diplomas levels in humans safely and sustainably in the standard dosage group, any plus increased by forty percent after four weeks, and that's pretty good, and in the double dosage group, the any plus increased by ninety percent, and that's actually pretty good. The best podcasts that I've done recently. Is My podcast exploring em talk society. It's my review of the book E. M., F.. And the takeaway from the book is that we all need a lot more any D plus because of the significant threat that we face from Ukraine. Ems from WIFI everywhere and smartphones everywhere, and so if the patera still buying is having the effect of. Forty, percent or nearly doubling the. Plus to ninety percent. That's a pretty good sign. For out there. Who is you know worried about? How catastrophic of ems are going to affect our? Health. Let's talk about any not any but patera still buying as a mobility hack. There was a significant improvement in chair, stand and power walking exercises. The researchers speculated that NRP. T may support overall muscle, health and or energy in an older population. And it has an excellent safety profile out of the one hundred twenty in the trial one. Adverse effect mild intensity assessed as possible related to NRP T., and that was nausea so just one elderly person experienced a bit of nausea of one hundred twenty. That's really not bad, so the study also produced some helpful dosage recommendations. The Standard Dose is two hundred and fifty milligrams of Nicotinamide riboside plus fifty milligrams of Patera, still mind, and then the double dosage is five hundred milligrams of Nicotinamide riboside plus one hundred milligrams of Patera stillborn. So if you're not an elderly person, that standard dosage is probably just fine. And also note that the study was updated in two thousand eighteen year after they did it, and I really love it when scientists notice errors in their work and then come along and correct them. The book Rigor Mortis talked about how scientists are these a lot of times, too. Many scientists are people with these incredibly fragile egos, and they will never ever ever correct their science when they make errors. So, it's really Nice Win I. Feel like I need to just do some some plopping some Bravo ing Wen. Scientists come along and correct the errors that they may have made okay. So what is the science suggests about patera still by. First of all that it is a SA- to in hack. It fuels the CIRTA wins, which are the light switches of the genome and it decreases insulin resistance. As an antioxidant it suppresses Paul metric acid mediated insulin resistance. In HEP G two cells by reducing oxidative stress and triglycerides accumulation, according to a recent, Indian study, thirdly, it helps weight, loss and diabetes. It suppresses liver Bhaluka Genesis, a mechanism, not dissimilar to Metformin. which metformin. His interesting thing I never took it because I was just worried about the the smell. Check out my podcast, discussing met foreman ideal deeper into the the dark side of Metformin, the Smelly Nece, and that's something that you don't have to worry about with patera still bind. Thank God okay. Fourthly, it Bruce Beeby NF, which is the. Up Regulating. And F. and M. R. A, which according to a twenty twelve animal study. It also has an im- a positive impact on spatial learning performance. Spatial learning performance. That might mean that if you were. Going to be an architect, it might help you with that sort of thing might improve your Doolan back scores for example. Next it boosts dopamine, the neurotransmitter that empowers motivation, good mood and cognition. We could all probably do with a bit more dopamine. It contains important polyphenyls which improve brain performance and I watched some youtube videos out there typically when I'm doing these Meta analysis projects, I try to actually go and just watch every single youtube video about a given supplement. And, that's what I did with this and some of the Youtube Video, said that Patera, still buying improved brain performance by up to seventy percent and I will admit that at that point, said wow, really seventeen percent. You know that sound true, doesn't it? Unfortunately I have to report back that after scouring the Internet. I could find no supporting evidence for this. I'm sure that it probably improves. Bring performance, but by how much who knows. Okay. Let's talk about Patera. PATERA still binds COFACTORS. Notably. The EPI genetic vitamin AM N. Could be potentially. Could be potentially by Patera, still buying according to a scientific American article. Quote Any D. boosters might work synergistically with supplements like resveratrol to help reinvigorate by the cadre and ward off. Diseases of aging while resveratrol has hogged the anti-ageing spotlight over the past decade, unsung researchers in places like Oxford Massachusetts. Is that Oxford Massachusetts are Oxford Mississippi I am not sure with they're talking about. Their anyways have quietly shown that patera. Still Mine is a kind of extra potent version of resveratrol. The PATERA, still buying molecule is nearly identical to raise virtual 's except for a couple of differences that make it more bioavailable. I've used as virtual and frankly it did not blew my bio hacker socks off compared with a number of nutro picks I've tried. It was a pretty underwhelming experience, if I was to use resveratrol again or Patera, still by I would follow the advice of Dr David Sinclair. And what he said was that you can think of resveratrol as the accelerator pedal for the ser- to jeans and N N N as the fuel, so he is also suggesting combining these two things, so let's talk a bit more about. nicotinamide Mono nucleotides. That's an which is another entity plus precursor. I would choose and amend over the nicotinamide rival side used in the American study mentioned above. This science isn't clear, which is better though they both seem to deliver about an equal uptick in any plus levels, but according to a not significant, a not insignificant number of anecdotes and M N is more stimulating, it delivers more of the classic neutral effect, which is what a lot of us want. So I would modulate the American studies protocol a little and instead use an and patera still. Thus I would like to. It is by pleasure to present to you. The EPI genetic awesomeness protocol so this protocol will give you the epigenetics and insulin sensitization benefits. Of both the resveratrol and the turf, still Bein while allowing you to experiment with the N. dosage, some. Bio Report. That doubling the an-and dose to a gram daily makes a huge difference. Others find. That five hundred milligrams daily is impactful, and so you'll just have to experiment with this for yourself, and so I've got the protocol here in the article, and it goes something like this month. One you do five hundred milligrams of. Daily and fifty milligrams of Patera, still buying daily month to five hundred milligrams daily two hundred milligrams resveratrol daily month, three one thousand milligrams in an daily fifty milligrams. Tara still by doing month four thousand milligrams daily fifty milligrams, reservatrol, daily, and then month five five hundred milligrams daily fifty milligrams. Daily and fifty milligrams per still buying daily. In the final month as you can, as you'll be able to see if you go and check out the protocol in the article which you are going to want to do if you want to implement it. In the final month, you would take all three together. However I suspect that this is a bit of overkill. Struggling with a serious chronic condition, these studies indicate that taking resveratrol or are still by increases, the baseline n plus level for weeks, even after ceasing dosage when it comes to not natural compounds like these the effects on our health tend to linger, I think even with the one month cycles you'll enjoy some synergy between the pharmacokinetics of the resveratrol and potato still buying. So, in conclusion I give Patera, still buying a risk agreed of a I think it's fine. I think it's something that people should go out there and try and. I will conclude despite their similarities. It would be a mistake to rape to replace patera still bind with resveratrol. They work together achieving an anti aging effect. There's a reason why you find them together in nature in the skin of grapes. If you can afford to, you would probably want to take a little of both or cycle them as I suggest in the EPI, genetic awesome news protocol. If you need to be selective. If you're bound to buy a budget here, I think risk veritable. Is More for those suffering from diabetes, obesity or heart disease I would prefer patera still buying again because I don't have to worry about it. Robbing any of the gains of my aerobic exercise and I typically end my gym workouts with fifteen minutes of with fifteen intense minutes on the bike doing cardio, so treat your EPI genome right with things like Patera, still buying an that, we're talking about here, and you can enjoy guilt free the simple pleasures in life like a glass or two or three of Vino. That's my thoughts on patera still buying. If. You use it. Let me know I'd love to hear from people out there. That are using potato. Still buying that are using these exciting epigenetics, medicines and vitamins that I've been talking about lately. Drop me a comment. Draw me a message via social media. And share this podcast around again I'm Jonathan with limitless mindset, and I look forward to a continued conversation with you.

Patera Patera nicotinamide riboside youtube diabetes John Limitless nutro Bravo Di instagram respected Journal EPA nicotinamide dopamine M N Ukraine Jerrell rape NRP
Unlocking The Secrets of NAD+ in COVID-19

Precisione: The Healthcast

37:31 min | 8 months ago

Unlocking The Secrets of NAD+ in COVID-19

"Welcome to precision. The health cast where you will learn how to live your best and healthiest life by precisely understanding how your body works what it is made up of and how to optimize your health based on that information. I'm your host. Dr Marvin sank founder of precision clinic where we take a highly individualized approach to health wellness and longevity by helping amazing people like yourself understand more about their genes at genetics microbiome sensitive toxic exposures levels of inflammation and much much more for the purpose of creating a highly specific nutrition and lifestyle planned at is flexible and sustainable. I hope you enjoy this week's episode as much as I enjoyed recording it I everyone. Welcome to my podcast where we are dedicated to delivering the best and most accurate information regarding precision healthcare from the brightest people in the world. Today we have an incredible guests. And I'm so excited to speak with him today. We have Dr Charles Brenner actor. Charles Brenner is the Roy. J carver chair in Head of biochemistry at the University of Iowa as well as a founding CO director of the University of Iowa Obesity Initiative in two thousand four Brenner. Then a faculty member at Dartmouth College discovered nicotinamide riboside or are to be a vital precursor of nicotinamide. Adnan die nuclear tied or an plus which is made available by Nicotinamide riboside kindnesses or an arcade that are conserved between yeast and humans. In two thousand seven Dr Brennan's lab discovered a second pathway by which and our is converted to an e plus and showed that. Nra can extend the lifespan of yeast cells by virtue of elevated NA D plus levels and increasing the activity of the NASD plus dependent. Sir To time in the past decade. Dr Brenner has made multiple seminal contributions to any plus metabolism which include engineering a yeast strain to convert inexpensive. Na D plus precursor vitamins into an are solve the crystal structure of the human anarchy one developing the methods for quantitative any deep plus Matab. Oh Mix and demonstrating the activity of oral are in animal models of fatty liver disease. Obesity type two diabetes diabetic and Chemo. Therapeutic neuropathy aren't failure and central brain injury Dr Brenner also led the first clinical trial of our which established safe oral availability in humans is currently focusing on the maternal and neonatal affects oral. Npr and translating animal discoveries into evidence based safe human clinical practice for human conditions of metabolic stress. Charles Welcome to the show. Thanks for much. It's great to be with you feel like I just Introduced a biochemistry superstar here. Trying my best everyday. Let's jump right into tell us a little bit more about your personal background and how you came about doing what you're doing. It would be my pleasure so I've been working in laboratories since I first or second year in College at Wesleyan University and I graduated from College in Nineteen ninety-three work sometime in the biotech industry and then Was a biochemistry at Stanford University as well as a as a PhD in cancer Biology and throughout my independent career. I've been interested in class of molecules called nuclear tides and your readers. Know what you know. A. T. P. is right and a T. Gnc being components of our Rene and DNA. But I've always been interested in the sort of noncanonical nucleotides funny nuclear tides and for the last fifteen her almost twenty years now. I've largely focused on the metabolism of de Nicotinamide Adnan's dynamically tied. This is the central catalyst of metabolism so. I love Metabolism and. I'm interested in all things in a D. And how many conditions of metabolic stress you named a number of them. Neuropathy fatty liver abusively central brain injury post-partum and now we understand a corona virus infection many conditions of metabolic stress disturb the NASD system and disturbs cellular resiliency and and function at the organism level. So as you mentioned You Know Corona Virus Andrew. Stand that you're doing some research in Corona virus recently and I saw an article in the La Times About this as well. Can you tell us a little bit about that? And what you're looking into absolutely so a virus is a disruptive little program you could almost call it. doesn't live on its own. It gets into cells in order to go viral which literally means make lots more viruses. So it hijacks the metabolism of what we call the host the infected cell or the infected organism to make more viruses and it needs host metabolism in order to to make virus. And what we've discovered is that when corona virus has gained entry into animal cells they disturb the NASD system they disturb the central catalyst of metabolism and the host is trying to use its NASD to defeat viral replication and the host system gets depleted and altered by viral entry. So we think that there are clues to buildings cellular resistance against viral infection and this would be boosting the innate immunity not only corona viruses but to many other viruses that we've shown attack the NA system so potentially you're looking into the role of any may be boosting the immune system so that the corona virus is able to replicate as readily. Yes exactly so. This is not vaccine technology and know we absolutely need vaccines. We absolutely need hand. Washing and gloves and public health measures but building resiliency and resistance to the virus is something that we are focusing on there's potentially uses of nicotinamide riboside Nigen in Covert nineteen treatment as well because there's evidence from small clinical trials that healthy older people given high doses of Nigen have lower levels of inflammatory markers and as you know the site of kind storm as a component of of nineteen disease. So we think there's potentially a role for boosting ad in viral treatment but our primary interest in our first publication in the corona virus realm relates to building defense against the initial infection and the initial establishment of the disease. So it'd be more of a preventative strategy okay. Very good How far along are you to publishing anything with regards to that? So he's just in the middle of it right now. Well we've made our first publication. Our first publication is online in what's called the Bio Archive if you follow me on twitter at Charles M. Brenner you'll see links to to our first corona virus paper by archive is where scientists put their newest work. That is in the process of Peer Review and our work is under peer review for vetting by others in the scientific community but the work is out there and it shows very specifically how different corona viruses including SARS Cov to the causative agent of covert nineteen. How when it infects a ferrets. And even a human patient that died of the disease the NASD system is very specifically disrupted a bunch of genes. Go up there trying to defend against the virus in a bunch of genes. Go Down and this tells us the ways in which we may be able to defend cellular health by boosting the system. We we show in a number of different ways that the NASD system is under attack by these corona viruses. We have upcoming work on how flu virus and other viruses affect the NASD system. But it's very clear from the work that we've already put out on the Bio Archive and that is in Peer Review. That Corona viruses attacked the any system. In what we consider an actionable way so potentially repairable way that would allow greater innate. Immune defense fascinating. Can you tell us a little bit? About what the difference between for some of us who don't know and are in a D is because they we often hear these two names Hand in hand side by side with each other and sometimes people don't understand what the differences between the two absolutely so D. is a cellular coenzyme. You know the advanced listeners to your podcast will know. There's actually four different. Nasd co-enzymes Eighty Plus Sunny D. H. Any DP and any P. Ph and these are the central catalysts of metabolism. They allow our bodies to convert everything that we eat not only into ATP that powers ourselves and our mechanical processes in our ability to pump blood and run and thank but metabolism converts. Everything that we eat into everything that we are right so every protein in your body every nucleic acid in your body every lipid in your body. Every molecule of estrogen and testosterone the proteins in Your Islands. Everything is manufactured by your own body and depends on metabolism depends on forms of any D. as the catalysts any D. Has To what are called phosphates in it and ADP and h three phosphates in them and so even though we eat things that have any D- in them any has to break down into vitamins. That go into cells and the cells convert the vitamins into the co-enzymes. So you eat. Foods that have micro nutritional content so that you can make more co-enzymes the vitamin forms of an ad are basically niacin and nicotinamide and the one that we discovered nicotinamide right beside nice and forms of. Niacin were discovered in nineteen. Thirty eight you said. In the intro my group discover nicotinamide riboside in two thousand four and so an our nicotinamide. Riboside ISN'T ANY PRECURSOR VITAMIN. It's something you can take a supplement. It's been commercialized. As Nigen and it allows your cells to get back up to the NASD levels that they need in order to run optimally as I said a number of times and a comes under attack by conditions of Metabolic Stress Neuro Degeneration Obesity Diabetes Central Brain injury viral infection sun damage sunburn. Dna damage reactive. Oxygen species disturbed the NASD system. So there's a call for more any D- precursors when cells are under metabolic stress the genes that you described earlier that we discovered the nicotinamide riboside kinase genes are essential for converting an are as a vitamin into Ad. Those genes get activated when cells are under stress so for example in heart failure. Any D- goes down nicotinamide right beside kind as to gene. Goes UP WHY because the failing heart is looking for NPR in order to fill up its NASD stores. When the corona virus infects have sell the nicotinamide right beside kindness genes are also up regulated so the gene expression program of souls that are being challenged by metabolic stresses including this virus. The gene expression program is telling us that they are looking for an are in order to restore their home stays and cellular resiliency to the bodies programmed to want this. That's the kind of like a mechanism that happens under certain stressful type of situation to your health to your body. The fundamental theme of Biology is Homeo- stasis right that when we get we wake up in the morning and you know we have an empty stomach when we're all you know when everything's working optimally and the empty stomach secretes Gremlin. Which tells the brain get out of bed and go and hunter gather some food or go to your fridge and get some food right and then as you fill your stomach than your fat starts secreting. Leptin in which says okay enough already. You know. We're starting to get you know. Satiated and so in optimum health. We have these feedback mechanisms. That say more of this less of that. When a de- comes under attack there is a gene program that is there to try to get your energy levels back and part of the gene program. That really helps us. Is the NICOTINAMIDE RIBOSIDE. Kindness jeans get up regulated. And so if you're taking and our supplement than your body is able to use the supplemented and are in order to boost. N. A. D. Levels and and boost these kinds of cellular defenses because I guess under certain stressors. Perhaps the body can't keep up with the amount of any that it needs. And so that's a place where the supplement may be able to. Kinda help offset some of those deficiencies that kind of one of the points. That's the the idea. Exactly that in the perfect world in which we were you know hunting and gathering all of our food just like you know the wild. I live on a farm outside of Iowa City and have opportunity to see lots and lots of wildlife you know Furry creatures birds frogs all kinds of stuff and they spend their day expending the same number of calories that they take in right so a wild mouse not a mouse in a cage but a wild mouse spends all night because their doctrinal foraging for food and taking in an expense. The number of calories that it takes in and so it's in balance right and so that animal is able to get everything from its diet and self repair and so forth and so on but we have a very disrupted environment we're exposed to overeating and not enough activity and alcohol and Sun and reactive oxygen stress and timezone disruption. Although there's less of that because we're not getting on planes so much right now we're recording this on. May Fifth of twenty so most people are working from home and all of these things are conditions of metabolic stress. Over eating over drinking in activity timezone disruption sleep disruption infections sun damage Cetera and so under all these conditions of metabolic stress. There's a use case for a D. enhancing supplement and nicotinamide. Riboside is basically the biggest piece of energy that can get into a cell and a man can't get into cells. I don't know why people promoted because it's got a phosphate on it and it can't get into cells but nicotinamide right side is a large piece of D. that can get into cells and restore the NASD that ourselves need in order to self repair. And when we're talking about Alex stress we're also talking about motto conrail dysfunction as. Well I guess right yes so Mike Okon. Ria are a big part of cellular health and in the function of nearly all cells in our body of red blood cells. Don't have my conrail but pretty much everything else does. And you know that's where oxygen is consumed and oxygen is what we call the ultimate electron acceptors so we need to conrail health and might congre depend you know intimately on healthy energy levels. I hope you're enjoying this conversation as much as I am. Let's take a quick break and talk about Sun Genomics. This is an incredible company. They are testing your gut microbial and looking at what it needs and creating precision probiotic just for you. Check it out now by going to. Www DOT son genomics dot com? And just as A. Thank you for listening to our podcast today. Giving everyone my discount code m s two five so you can it a try at a discounted price. Now let's get back to the show and what happens to our energy levels as we age and is there a particular age were you know changes start to occur. Well the funny thing is that in a D and I hate the word. Anti-aging I never use it. Anti-aging to me sounds like something fake and I actually I embrace aging I want greater maturity and capacity. But of course I don't want you know incapacity and so I'm interested in healthy aging most of the people in the NASD field. Talk about aging much. More than I do. I can measure striking attacks on the NASD system in conditions of metabolic stress like sun damage and alcohol and Fatty Liver and Gerda generation and. Yes there's evidence that any declines in aging but I'm not convinced a doctor saying that it isn't episodic so maybe it's that cumulative episodes of Sun Damage and bacterial environment infection and over eating and alcohol are really the root cause of any decline in aging for example. I like to say that if you were to look at the photographs of a cat owners hands you know over decades and the cat owner got scratched by their cats. Let's say their cats are big cats with big big claws? You would be able to order those pictures. Chronologically I last. But aged in 'cause those scratches cats caused those scratches and so there is a temporal connection between decline of any D- But I'm not sure that it's time itself that is the cause of any Decline and it's for certain it's conditions of metabolic stress that attack the system. But it is a repairable thing. Human clinical trials that we've run and others have run on that you know within a number of hours oral nicotinamide driver's side is converted into higher blood an AG and within a week the blood and a D is at a higher level and within two weeks tat the high plateau that is achievable at particular doses of at our safely. So we think that boosting and has a use case in you know basically optimizing health. And how does any impact things like fatty liver for example? Does it help reduce reductions in liver enzymes mobilization of fat out of the liver kind of? Could you kind of talk us through some of those showers scenario right? So we're putting this together from a combination of preclinical research. Which is you know mostly in mice and rats and the earliest human clinical studies so in a mouse we can induce obesity and type two diabetes in a matter of weeks right and we can treat it in a matter of weeks and what you see in a mouse. Is that when you give the mouse in a pretty high doses of nicotinamide driver's side? You can get them to stop their weight. Gain on the worst imaginable diet. And you can improve the level of the circulating liver enzymes. You can clear the fatty liver and you can lower. Their levels of blood glucose right so then people try this in human clinical trials and the first human clinical trials. Were too small done for too short a time period and didn't necessarily have the best primary end points. I don't WanNa get too technical on this but we have an editorial coming out. It's flu hardy Brenner. In the American Journal for Clinical Nutrition and again I'll provide a link on my twitter at Charleston Brenner that shows that summarizes three clinical studies one was done for three weeks. One was done for six weeks and one was done for twelve weeks. I was involved in two of these. Not all three of them but the message that's coming out is that it looks as though nicotinamide riboside can potentially improve markers of inflammation in as little as three weeks can improve body composition in women meaning more lean mass less fat mass in as little as six weeks and start clearing fatty liver in about twelve weeks in men and guess what none of this has been combined with exercise yet and we all know that increased physical activity should really be the standard of care for all of us just about all of us as you know people that live in western relatively affluent societies walking and running and climbing stairs as much as we should. We have too much access to food. We're almost like laboratory animals in that were combined in cages with access to high fat diet. Right and in my flu. Hardy and Brenner editorial work saying it's time to combine and our with exercise where all of the enrolled participants should have physical activity coaching. That says let's do you know ten or fifteen thousand steps a day or high intensity interval training or something. I don't know what it should be. People can design different kinds of trials that have where every participant has increased physical activity. And we know that that's going to improve some of these things like lower inflammatory markers improved body composition and start mobilizing liver fat then. What we think is that when we combine the increased activity within our so. It'll be everybody is has increased physical activity and then it's placebo or an. Are we think that the and our group is going to be synergistic with that lifestyle? Change and you're really going to see you know frank weight loss and improved like CMEC parameters and remarkably improved body composition. So those trials haven't been done yet but the safety parameters for those trials has been established because we know that in our is safe up to one or two grams a day. The manufacturing process for Nigen is a clean one that has undergone safety review. And it's a compound that's generally regarded as safe and it's a new dietary ingredient and there have been studies in which it's even been considered a A new investigational drug applications. So so we're excited about the future of nicotinamide right beside research and We want to establish evidence based use case for Supplementation within our to prevent and treat conditions of metabolic stress and many types of metabolic stress. That's awesome You know just I was just thinking as you're speaking that the way that a lot of us here in the states thing as well he knows something is really good. I WANNA I WANNA have a lot of it. And so you know one of the trends these days isn't getting IV therapies and people are starting to get any D- infusions as well. Is there potentially any harm that could be done and taking high doses of certain you know things like that for example or is there main? We may not know there's harm in doing things for which there's no safety dossier my so. I don't know what they're injecting. I don't know what the safety parameters of that stuff is. I don't know what the health consequences of taking IV infusions. I don't consider that a safe or evidence based practice nor does the biochemistry of it make any sense because any D has two phosphates on it. It's not cellular available any a D. Intravenous and a d. may be delivering and are into the bloodstream. But nobody knows that because there haven't been any trials of what that is doing and there's certainly no safety assess for what that's doing. I've heard that Lots of people are buying something called. There's no evidence basis for that whatsoever because we know from animal studies that in cellular studies that has to be converted to NPR in order to enter cells. And there's no safety dossier on an either so an are is the safety tested evidence based way to boost N. A. D. Unlike Niacin. It doesn't cause a flush unlike nicotinamide it won't inhibit some of the enzymes that were trying to activate and so No I would not advocate for intravenous. Nasd or other approaches to an ID. Boosting that have a safety dossier wonder how they're even allowed to be produced. And if we have no data on the safety of it it's funny. It's not funny. It's very worrisome. For me as someone that you know spent my you know the last fifteen or twenty years working on any D- metabolism and you know at just at the point where we've taken something all the way from yeast into animals and humans with safety and concern for not harming people. There are there unauthorized suppliers of an are that are free riding on our safety dossier and that manufacturing in unknown places to unknown safety standards. There's a man which has no safety dossier there's intravenous and a D. which has no safety dossier. So I really am very concerned that people could be hurt and that you know it's really an abuse of of the scientific process and and even the commercialization and patenting process. It's it's a real concern of mine. Yeah I see this a lot in a lot of different things. Not just any diesel. Why it's nice to have experts like yourself In the field actually talk about it so we can tell the public. What is the truth? Not The truth so that they can try to do the safest thing for themselves so I appreciate it Are there any other research projects that you guys are working on these days? Well the things that we're most interested in our conditions of metabolic stress that disturbed the NASD system and just three or four realms. That really fascinate us. One is that we discovered in the last couple of years that post-partum you know and I'm not talking just about postpartum depression which affects a you know a fraction of new MOMS but the process of postpartum itself. Where a new mom? Her body has been transformed during pregnancy. In order to create this human being and in the case of of mice and rats you know half a dozen or or ten Offspring and then upon delivery is transformed again in order to have her memory deliver in all of the food that the new babies need. This process is a metabolic disruption and this process disturbs the NASD system. It turns out that in mice and rats if we support the lactating new mom with nicotinamide riverside. We can improve her milk quality. We can improve her postpartum weight loss and we can improve the neuro-development of her offspring into their adulthood. Actually and so we have a very exciting project that we're doing with the bill and Melinda Gates Foundation in order to understand that process further. We want to understand it. More in animals and then we want to put an boosting strategy potentially into human clinical trials with MOMS and low and moderate income countries. And who are clearly under metabolic stress when They've had a new In in non optimum conditions. That's one huge area for us. We're interested in a number of types of cancer that disturbed the NASD system. Were interested in virtually every type of neuropathy diabetic neuropathy Kema therapeutic neuropathy some kinds of central brain injury that affect the NFC system. And then as I said earlier we're very interested in viral infection and how viral infection disturbs the NASD system in? And whether that's actionable whether we can boost sawyer defense and and defense at the at the human being level with higher end status potentially using something like Nigeria fascinating excited to see some of these papers when they come out. Are there any final special pros? You may have that you'd like to share with our listeners. Before we wrap up well I said this earlier. I think that increasing activity is a key to you. Know healthy aging and healthy living physical activity and mental activity are great. You know Making sure that our our diet is as good as we can Have it and have it being balanced with food intake being balanced with energy expenditure? I think there is a use case for boosting energy with something safe and clinically tested like a nitrogen and if people want to follow me on twitter at Charles Brenner. They can ask questions at at anytime. I'll do my best to try to put them into lay person's terms while still being evidence based they can look up Our publications at Renner DOT lab dot EU Iowa Dot. Edu and they can learn more about any D. at about a dot com. So thanks very much for for having me be very pleased to take people's questions on twitter. Awesome thank you thank you so much for being a guest on the show was amazing discussion and I really enjoyed it. I'm sure everybody else really enjoyed it as well. Terrific with my pleasure and Thank you to all of our listeners for tuning in today to listen to another exciting episode of precision the healthcare. We hope you've enjoyed this episode of precision. The health cast the one and only podcast truly dedicated to helping you understand how to live long and personalize your health. I'm your host Dr Marvin Sink until next time. I WanNa take a moment to tell you about precision clinic. A unique medical clinic that I founded in two thousand nineteen precision clinic is the only practice in the United States that uses precision omits to help optimize health and improve longevity by using cutting edge science and technology to create highly personalized recommendations and protocols. No matter what your health goals may be give us a call and learn more about our customized and comprehensive evaluations. That can all be done from the comfort of your home by telemedicine. Our phone number is eight. Five eight two two nine seven five eight nine or you can email me at Admin at precision clinic dot com ad m. i. n. f. p. R. E. C. S. I. O. N. E. C. L. I. N. I C. Dot Com. We're looking forward to hearing from you.

NASD nicotinamide fatty liver Charles M. Brenner twitter Npr viral infection Dr Charles Brenner Riboside Niacin Adnan nicotinamide riboside Corona Nicotinamide Adnan Nigen Obesity Dr Brennan Dr Marvin University of Iowa
Dr. David Sinclair on Informational Theory of Aging, Nicotinamide Mononucleotide, Resveratrol & More

FoundMyFitness

1:22:01 hr | 1 year ago

Dr. David Sinclair on Informational Theory of Aging, Nicotinamide Mononucleotide, Resveratrol & More

"Welcome back friends. I know that many of you have been waiting a long time for this release so I can't tell you how genuinely excited to finally get to share today's episode with you disc episode features Dr Davidson Clear. David is a professor in the Department of Genetics at Harvard Medical School and Co Director of Paul F Glenn Center for Biological Mechanisms of aging. David is also a CO author of the book titled Lifespan. Why we age and why we don't have to which is out now and available on Amazon in this book? David goes into great detail about many of the topics. We actually discussing this episode particularly his theory of aging known as the informational theory the aging. So that is a really great way to learn more about what we talk about today. I thoroughly recommend checking out his book in this episode. David and I discuss us. How caloric restriction fasting and exercise increase levels of a molecule called? NHCD and how. This activates are two in a family of enzymes involved in longevity in addition to activating two inns how any is essential for McConnell metabolism and function but also how it's required for repairing damage to DNA by activating debating. An enzyme called Park. We discussed how energy levels answer to an activities decrease with age and how animal studies suggest that raising cellular energy levels can trick the body into thinking it is younger. How plants produce compounds at activate Sir two and pathways in plants in response to stress and intern the compounds compounds activate beneficial pathways like the search in pathway? In humans a phenomenon called Zeno hormesis how reservatrol is a Zeno hormetic compound pound and is produced one great plants are stressed either in response to fungus or lack of water how virtual enhances the binding of Sir Tunes to any thus making certificates more easily activated for a longer period. How a phase two clinical trial involving people with Alzheimer's disease showed River resveratrol improved cognitive function lowered markers of Activated Micro Gloria and more how Rivera has been shown to induce a tough G by directly inhibiting? MTR THROUGH ADP competition in mice however is virtual exist as a trans isomer and the Trans resveratrol is believed to be the most predominant in stable of the two forms. How trans-resveratrol should be protected from light? How both in the Tim? I'd riboside and Nicotinamide Mono nuclear tied have been shown to improve cognitive function and brain pathology in mice that have an engineer to get a disease similar to Alzheimer's disease. How older mice that were given nicotinamide? Mina nucleotides experience delayed aging in the liver muscle immune cells eyes and bones but those that took a lower dose of nicotinamide mono- nuclear tide. I'd had improved mitochondrial function and enhance physical performance. How there may be a threshold dose of Nicotinamide riboside and Nicotinamide Mono- nuclear tied? That needs needs to be crossed. In order to override delivers first pass clearance mechanisms so that nicotinamide riboside and nicotinamide mononucleosis can raise energy levels and other tissues like skeletal muscle. How there may be challenges and translating animal studies on Nicotinamide right beside and nicotinamide mono nuclear tied to humans particularly due to the need need to determine the dose required to promote health benefits? We also discuss Steve Horvath EPA genetic aging clock which measures DNA methylation groups and how they may play a role role in widespread gene regulation including Sir to jeans and how you may participate in resetting the clock how the signal that resets the EPA genetic clock in mice ice involves the Yamanaka factors a group of four transcription factors that can reprogram and adult cell to become a pluripotent stem cell. That can form any cell type. How short term treatment with Yamanaka factors can reverse cellular and physiological homer hallmarks of aging and prolong lifespan in mice with a premature aging phenotype phenotype how fasting exercise and other lifestyle factors may slow the rate of EPA genetic aging but may not be sufficient to reverse it like some of the powerful Yamanaka factors may be able to do? We also discussed Dr Sinclair's hope that we may eventually find a way to induce Yamanaka factors in a way that is more safe applicable. Oh to humans than current genetic engineering in viral techniques use. An animal research can do and so much more a few things. I want to mention before we ought to this amazing podcast. In addition to this episode I have put together a bonus episode that sort of focuses on my personal concluding take on everything. NASD nicotinamide right beside and nicotinamide. Monica tied that episode comes out to the wider world sometime next week and should be of great interest to anyone that enjoys this conversation today. Having said that if you are a premium member you can get a pre release of that episode right now. That's right right now. By grabbing the brand new members only podcast feed the members. Only podcast feed. What's that you may ask? This is a cool new way to get occasional early access to upcoming episodes some exclusive zip content like my members only QNA's and more that's not the only benefit premium members get either along with already great notes released for free with every episode for members. were now including a convenient powerpoint where you can quickly skim. All the graphical figures steady quotes and more usually reserved for the video only just by way of example. The presentation for this episode comes with over one hundred fifty slides. That usually you'd have to watch the entire video to see which seems mighty redundant if you've already listened to this episode all the way through this new suite of real concrete benefits reserved for premium. Members is my special way to give back to the people that automatically enabled me to build my fitness into the amazing largely free resource for the wide world that it is learn about all of these brand new benefits more than even make sense to go into right now as well as the back story and motivation or even get signed up for a dollar per month by heading over to foundmyfitness dot com forward slash premium. That's found my fitness dot com forward slash P R E M I U M premium. If you already ready are a member you can access all of these new benefits in. The new members only dashboard on my website from the dashboard members can access the hundred and fifty powerpoint appoint slides at a company. This episode the early access podcast feed with my concluding thoughts on NASD nicotinamide riboside nicotinamide mono nuclear tied my private it notes that I use to warm up before the podcast as well as sign up submit questions and check the upcoming schedule for my upcoming question and answer sessions to you. Get the members only dashboard head over to found my fitness dot com forward slash dashboard. Once again that's foundmyfitness dot com forward slash dashboard dashboard and now finally onto the podcast. Welcome back my fellow foundmyfitness longevity fanatics. Today is a treat. My guest is Dr David Sinclair a professor in the Department of Genetics at Harvard. Medical School where he researches tries to understand the biological mechanisms that regulate late the aging process and how to slow them. I can't think of a more interesting question than understanding the biological mechanisms that regulate aging and how to slow it I'm very interested in it myself for sure. Well thanks Ron. Thanks for having me on. So what are the mechanisms. What is the secret to the universe? Will I've been studying this As you know for over thirty years now and when we first started out we nothing and then we went to little ye cells and then we worked our way up to worms and mice anelle myself an probably a couple of dozen other researchers around the world have broken through a barrier of understanding about why we age and how we can actually reverse it. Wow so what's the what's the breakthrough thro well. There were a number of breakthrough in the nineteen eighties. The big breakthrough was that there and early nineties that there are genes that control aging we call these longevity genes do not hot cold anti-aging genes we don't talk about anti-aging we talk about longevity and health span and so these longevity genes were first found in organisms like nematode warm title one Andy Cells that we used for baking bread and that's where I started my career at Mit with lenny guarantee running up And those same jeans are our in our bodies and in pretty much every life form on earth and what we've discovered. Is that when you go for a run or your fasting. The reason that those beneficial official actually is because they trigger those longevity genes to repay your body and and make sure that you don't get as old as you would otherwise I ah just as a sort of a side note because you mentioned these longevity gene jeans and the worms one of the first so I was in college I went to ucs St in San Diego. And I was a chemistry major And I I worked in Biotech at the time. It was the sort of start up. It was aluminum and worked in the chemistry department. That was a very big company but I was working there my junior and senior in college and you know it was sort of like I was making peptides and doing a lot of organic chemistry and and after a while I just didn't feel like very interested anymore so I went to this institute to kind of get a little bit of a taste of biology because believe it or not. I didn't have have a lot of biology classes as a chemistry major Had A few but it was mostly just you know chemistry And I I I joined Dylan's lap and Who Uses nematode worms to understand the genetics of aging? And I remember the first time I was working with these these worms that had a decreased. Insulin Igf Wednesday telling pathway How they lived like hundred percent longer and how they relate youthful when they were supposed to be dead and I saw it with my own eyes and it was doing experiments and it was like holy crap? This is cool. I we have genes that are similar to these little worms and they are like this. You know so so that kind of got me interested in at least on the genetic side of aging well. I'm not surprised. Even I don't do all the experiments my lab. You may be surprised to know and people tell me results. All the mice are living longer. Downstairs is on the enemy or whatever we've accelerated aging in mice because we've tweaked the EPA genome. And this all sounds great. You know go back to my email. It's not until I go in to the animal room and I see them with my own eyes and these are living creatures that are getting older and getting younger. It really is impact to actually see and hold them with with your own hands So yeah that's that's the thrill even with the East studies that I was doing back in the late nineties I was very intimate with the cells. It sounds sounds weird that you could really adore little microscopic organisms. But you look at the microscope and they live for about a week and you have to monitor these mother cells and they a little daughter cells that you picked off used to pick off with a microscope and a little pick. You get to know those cells pretty well you don't give them names you give them numbers But when they were getting a big fat old sterile and then they died. You know. There's a little twinge of sadness that these little dudes that you've been looking after all the time or or females in in this case Were dying so I think we biologists we get attached to these living organisms and it's really rewarding to see that when we're we're not making them sick we actually making them live longer and healthier lives right so I became with your work back in those days when I was actually doing doing research on these little nematode worms. And I remember. The some of your work was on resveratrol And how reservatrol control like help to regulate one of these longevity pathways Sir Tune this or tunes and how that was involved in basically if you could activate them certain ones seem to delay aging so maybe you could talk a little bit about Both Sir Tunes and also what is very trial is. Uh Let's start with you and so when I arrived at mit it had just been discovered. The gene called Sir for that when it was mutated would make diesels live longer and a fair fairmount work We figured out that the so proteins which are enzymes that control gene expression genes on and off That would become regulated over time and we found out that's because they were being distracted by a whole bunch of DNA instability. That was accumulating in themselves but the the lesson was that the ser- to and enzymes times that we're controlling genes were also controlling lifespan. which is a real breakthrough? No one had really expected to find Jean regulators controlling aging. We thought we'd find antioxidant produces DNA repair proteins. That's not what we found initially. And so the SORTA became Very interesting in east and Matt Cable on WHO's Now out in Seattle He's a leader in the field as well he came in and he's first project in the lab was to put an extra copy of one of surgeon's number two two into yeast Those easily thirty percent longer and later Lens Lab in my lab at Harvard showed that this was through a process of mimicking calorie restriction. If you have a lot of cer- tunes you get the benefits of calorie restriction on dieting And other types of little stresses on the cell like heat and like amino acids and if you get rid of the search in a search you gene. The real breakthrough was that now calorie restriction. It doesn't work anymore. And that whole setup was the basis of most of the research that the field has been doing since two infield trying to understand that concept of what we learned in Nineteen Ninety S in our bodies in mice And I'm I'm lucky and happy to say that a lot of it is very similar Laura. Nobody's as well. And when you say calorie restriction usually you're talking about for like in mammals and humans like eating thirty percent less than you normally white or something. Yeah well in the old days We typically would take out thirty sometimes even forty percent of the food or the mice and they'd be hungry all the time and it wasn't very pleasant with yeast if you're wondering calorie strict yeast. We just dropped the level of sugar in the Petri dish I think it was five. Fold and that was enough to make them live longer. They still grew quite happily these days as you're aware intimate and fasting seems to kick these longevity genes into action to instill come on but you don't always need to be hungry. You can eat four days of out of a week or even six days out of week and still have a period of fasting that gets this to an activity up to the levels that we think would be beneficial. Yeah and there's there's certainly a lot of overlap At least in the in the scientific between calorie restriction and intermittent investing having beneficial effects variety of beneficial health effects. But I do I. You know some of the differences would obviously be you know when you are in the minute fasting your your shifting your metabolism from carbohydrate glucose to fatty acid metabolism. And you start to key to genesis assist can kick in after at least if you're doing more prolonged type of Internet fast so There are certain a little bit differences as well between they tried one thing. That's interesting that connects everything is so we showed in two thousand five and a science paper that when you take a calorie restricted rat and look at its organs. We looked at the liver and muscle the levels of one of the two genes. The number one we have seven of these genes so we looked at number one because we we only had an antibody in those as to number one it went up dramatically. I think it was about five to ten fold in levels in the calorie restricted livers and then we recapitulated cal restriction in in the Petri dish we grew cells in serum from animals that had been calorie restricted. And we found that that was also enough to stimulate this boost of serotonin production but getting back to what you did. In Anti Dylan's lab. We found out the reason it went up in the dish was because of having low insulin and Niger if one levels because when we put back in normal insulin levels and on the search engines went back down And that was a nice link between for for the first time in mammals calorie restriction and the insulin pathway and actually in those days it we were fighting amongst ourselves that we were going through a paradigm shift which is always stressful. And Andy was saying my pathway is more important to ends and then there was the MTO people saying no. We've got the most important pathway and I'm trying to say say hey folks all the pathways are important in fact they're all talking to each other. We showed that so tunes and tour talking to each other so fortunately in the field now. Now we've grown a little older and wiser and we are in agreement that there is this network. It's not just one straight pathway from food too long life and that you can tweak one way and the others will also come onto help something that comes to mind when you so talking about really this important role that calorie restriction attrition intermittent fasting plays in activating this ser- to pathway and also Deactivating things like the insulin signaling pathway and Jeff One pathway I it is the the fact that the two are regulated by Something called any D- NICOTINAMIDE Identifying nicotinamide Mike Deneen dynamically died so plus but that is something that actually those levels rise during a fasted state they showed right and in response to exercise as well and So the reason is so exciting compared to the nineteen eighties when we thought it was just a housekeeping molecule for reactions is that the levels of an ad go up and down depending on not just what you eat but whether you're exercising and even what time of day it is so during the day your energy levels will rise and then you eat a big meal and they'll go down again and we we think it's one of the reasons you also get jet lag is your MD cycles are out of whack. Is it honest. Circadian Rhythm is it completely regulated by by meal mill intake It's it's a combination. It will be going up and down with succeeding rhythms mostly. But you can adjust what about knock Granado train composition lake if you eat more high-fat versus carbohydrate. No one knows that that would be a good experiment. Security Infield hasn't looked at nutrition as far as I'm aware of but what I can tell. Oh you anecdote. Only is that if I raise my ad levels. When I'm traveling? I feel a lot better if I had a shot of an booster in the morning when get to Australia which I traveled to pretty often and so I don't know if it's truly working. We need more than one person in the clinical trial but it fits with the mouse studies. which is that you can use an to reset your clock? What's interesting about this? Is that in. A D isn't being driven by the clock. The clock is being driven by an okay. Yeah so for people that are viewing or listening the clock. Meaning the what's re- regulating circadian. Rhythm Yeah your organs coordinate donate what time of day it is and when you're jetlagged your brain might realize that it's morning because your eyesight See Sunlight but your liver still thinks the middle of the night so you feel queasy feeling and the reason why is I mean anybody is really important for a variety of metabolic. I mean it's required for metabolism. Listen for metabolism metabolize glucose metabolism fatty acids Andrea need it But it's also important for a variety of other tissues as well well. Activating two INNS and DNA repair enzyme. Par Right you could argue that n the most important molecule in the body maybe with the exception of ATP but without either of them. You're in about thirty seconds so any D- ATP were probably the first two molecules that life on this planet used to survive live and it's to me as well and so isn't it interesting that the amino acid levels ATP and of the three main molecules it kills in our bodies that sensed as to what our environment is like and whether we need to hunker down and survive or go forth and multiply and those are the three main pathways this economy which is the metformin pathway in his tour which is rough mason. Which I'm sure you and many of your listeners are aware but we're tapping into very early aspects of of life that's found all over the planet and that's why I think we're having such big effects in animals? Often people say it's too good to be true. You know you tweet one pathway and all this good stuff happens while these pathways that have existed for going back. Probably more than three billion years and we're only I'm just learning how easy and seemingly safe it is to tweak them So energy levels decrease with age. And you think this is a causal for plays a causal role in the aging process. Right right so what was linked to and so so tunes or enzymes This is my peter of an enzyme but things like pacman. That's chewing off chemical groups of other proteins telling them what to do like a traffic cop and doc without they don't work this stuck shut and so there's always an idea around otherwise you'll be dead but if the levels go down as they do as you get older and I'm always almost fifty. He's somebody levels probably a half what they were. When I was twenty scary thought so tunes are working? Maybe half as well as they did telling the troops to go out because my body So when I go for a run I get less Benefit from that I feel tired. I don't make as much energy. Mighty country are down but by raising up the levels of eighty D to when I was young. What I think is going on based on the animal work we've been doing for many years now is to trick the body into thinking that it's young again or it's been exercising or dieting and that get allows the tunes to do their job the way they once did by by just having that level any higher like it's it's basically like a signal It is so think of it as the fuel in a car if the so tunes are driving and the resveratrol that we worked on years ago. works the same enzymes. But it's the accelerator pedal so it actually the NASD's making it work but residual come along along and make it work even faster so the combination of those two we find is even better than just one line call really Let me ask you this. This is kind of something that comes comes to my mind. I don't think it's often thought about this way at least in the field but You know because an eighty is required for cells does that are have a really high energetic. Demand like activated immune cells for example activated immune cells require a lot of ATP energy and a lot of any D- And if you think about like chronic inflammation how you know you're especially with as you get older and your unhealthy with age. You know basically it is it is increasing. If you're having more activated immune cells. Is there any way to test if like the day like there's a triage where enemies being sucked away to these activated immune cells the Mike Than Your Mitochondria are now suffering. And you might occur. Andrew will decay. Because because you're you're sort of shunting this eighty like take care of you know what your body thinks. This is potentially an infection. That could kill you right. So there's probably some sort of evolutionary mechanisms at play that say. Oh yeah immune cells need this any more than my to Andrea or something. I don't know so it'd be kind of interesting default. What I'm saying absolutely I think you're you're probably right been thinking along the same lines that as you get older. You're you're losing the ability to make an chewing it up and as it gets worse and worse as you get older. The immune system is a big drain on owning eighty And actually so is DNA repair with the activation of POPs and rainy a little bit. Then your pops and and your immune system would work. But then they'll they'll need more any of because you'll get more damage and this is a positive feedback in in a bad way that you once you start going down the NASD decline the cells start to need more and more and more with accumulating DNA damage. And that's actually what happens in yeast cells going back to those little critters that we found that they became became overwhelmed with damage. DNA and the cer- tunes were overwhelmed. They had to go over and repair that genomic instability edina instability. One of the reasons old old souls became sterile. which is a hallmark of east aging is because the tunes is keeping the cells fertile? Back here but they're so distracted by all this DNA damage. That's going on over here here that they lose their identity and that's a theme that we've discovered is likely true in mammals as well that accumulation of DNA damage distract the surgeons from their normal job of keeping with the proper gene expression and so their identity and we see the loss of sale identity over time in mice. At least and out what we're trying to do is to raise levels back up so that they can fix the DNA damage but also get back to where they came from and make sure the soul doesn't lose it's identity to launch at it. No Sir Tunes played a role a direct role in I guess they're regulating so many genes they're playing a role in DNA repair and DNA damage. They one of the first proteins to get to a broken chromosome really. Yeah we we discovered a while ago it was a it was a cell paper. Nineteen ninety nine if anyone would like to look it up mills myself and guarantee published that Sir to goes to a broken DNA end and then helps recruit cruised double double really. Select like like GAM- H. Two A. X.. So the first thing that happens is h twix gets lit up on the break and then within seconds sort one brings in hd one re helps remodeled the DNA in the chromosomes so that it's ready for the repair proteins to come in and without getting near these overpaid proteins very efficient. But they're distracted sir tunes should actually be regulating genes elsewhere. I think right. This is all part of My idea hypothesis called information theory of aging is that we're really losing the information regulation of time and all of these other things things that occur Such as Tillman Lawson a mighty Andrea loss and loss of produce aces and he would call it a protein folding mechanisms this could A. B. Upstream of all of that cells lose their identity and don't turn on the right genes the way they did when we were young but the trick is how do you get everybody ready to go back and reset and that's what we've been working. Well if you think about as you know Steve. Hoare bats work on on this EPA genetic clock and how he's shown now I mean several different cell all types including from humans that there's this very distinct EPA genetic aging clock that so what what I go to jumping Pinkas get get a little excited about this up. What I've been telling you about the tunes in the Movement we've shown is intimately linked to whole vast menthylatim clock doc really yeah? It's all part of the same process so this distracted protein. DNA repair system. What's happening is that happens? Is that you get metals was on the DNA that we use as a clock. But what what we're finding is that the clock is is a way of resetting the proteins go back to where they came from that there are modifications on the genome that say hey so tunes and these other proteins. Go back to that gene. Because that's where you belong twenty years ago and ignore these other changes which have come on since you were twenty and we've we think we've literally found what signal is to get them to go back now n as part of that you need the fuel. But what's the genetic trigger to say. Get off there and go back there and we found that and it's got to do with the Horvath clock being this is the publication. It's something we're writing right now for a journal. That's super exciting. That's really exciting has there. has there been any in in Oregon. Ebbert has there been any evidence looking at like for example like supercentenarians. What they're EPA genome is like doing brutal over there? The Horvath clock on it and is different than elderly for the for the same age. Yes right and actually the whole cokes has now been done on people who who are smokers or obese. It's clear in rotation tissues. Looks like ten years older than the same person like age match normal tissue. That's interesting because we're reversing the horvath's clock with our new found genetic trick and we're finding that we're having benefits if it's on those cells as well so I think this could be yeah and damaged neurons in this cool so it seems to be something radically new. So no Steve. While his his research is really interesting in that it is showing that it doesn't just predict your chronological age is predicting also also how long you have to live and Which is really interesting thing that if you've abused your body had a lot of smoking instead of Terry Steve can take your blood and he can say? Hey you're ten years older than you should be even if you let's say you were a previous smoker and you hadn't smoked for twenty years and if become active and healthy. Do you think that more. EPA Genetic Marker there or do you think that that I think it is. It's there well. We know the rates of cancer go down but all the other damage the changes to the EPA genome. What I've been drawing my hands this movement of proteins? That's one way street. It's not that if you suddenly start running in your sixties that it's all going to identify the signal will the signal. Yeah we've been putting that into animals and restoring aside in old mice and Growing optic nerves in old mice and it seems to be safe. They're not getting any new down by manipulating edgy. We now right. Wow right so we we use. We haven't published so my graduate student. One Changle probably kill me for saying too much but we both so excited even today. He sent me a text about a new breakthroughs that we've found not not only genes that tree them to move but then the genes that reset the clock. Once they get there really. You've identified the genes that can make the moot make the the methyl groups methyl groups and reset the methyl groups. And what says okay. Yeah okay so I'll give him to to the viewers and maybe this'll be published in shortly. We'll say so using the what's called the the Menaka factors and so the I I'm sure will the the first person to use these factors was Shinya Yamanaka Japanese scientist who looked through a lot of different genes and found a set of four factors. That if you put them into an adult cell say skin cell they would go back to being very primitive so primitive. What we call a pluripotent stem cell that you could then turn those cells into a nerve cell or even grow an eye? In the dish was a breakthrough that led to the Nobel Prize. Being awarded awarded him in two thousand twelve. He's take a person's can sell in turn into a neuron. I mean why not. We do a high school student can do that these days. It's not that difficult once typically weekly with science once you know how something works. It's pretty easy same with aging I think but what we've decided discovered is that first of all. I want to give a lot of credit to someone at the sole whose whose name is Juan Carlos. Belmonte good friend of mine and he's and he did the experiment that we were trying to do so just slightly scooped on that but he made a mouse where he turn on these four Yamanaka jeans and for short they stand for O S K and M and that mouse When he switched them on died within a couple of days? So that's not great for those mice but what he then clearly did was eating give up or his his post. Doc didn't give up. So what he did was he turned the genes on a couple of days and then stopped. Let the mice recover for a few days and then turn back on so the I feel for the mice because they they were headed towards death and they recover and then they cycled but actually they ended up being held here the premature aging miles model that he had Lived thing was forty beat plus percent longer but also he's showing since then that you can use these factors seem to improve wound healing and kidney healing so as he boosting their stem cell also pools and their second generating tissue. What I think he's doing what we're doing in the lab which is getting those proteins that have moved around and lost their way to go back to where they they were young and then reset the MRT clock and now a cell doesn't just think it's young using Chris Byrd? It's literally no he. Yeah well he might have but it was a transgenic mouse which means he inserted those genes into the mouse genome with an on off switch. Okay we don't do that. We use Viruses viruses that we can give to old mice. He has to start from a single egg. We can go into old mice within a few weeks. FIGURE OUT IF we've reversed aging in tissue in the whole mouse and we've also discovered that it's best if you don't use for those factors we have to leave one of those off because it's toxic it's the mic Jean makers and oncogene but the other three work great and the results that came in through The texts today use those three genes to protect neurons from dying in the mouse but also in the dish and the the gene that can restore the The whole clock was required and so very close. I think to to seeing the future of where maybe eventually we don't use viruses. Maybe we we have molecules that can do that. We can put in a drip or in a pill hill that can send us back another twenty years. Wow that's super exciting. I'm I'm like very pumped up about this whole epidemic clock research and linking being into you know basically being able to reverse reverse aging. I mean I think that do you know. Is there any evidence that fasting has any effect on that opportunity clock. Does that mean Sean. You know I have not seen that I think what I've seen from Steve's work and others is that you can slow the rate of the clock clock but I haven't seen reversal yet And I've shown Steve The results I just told you in. He's pretty excited. That someone's figured out. We think we've figured out why. Why the clock ages? What's causing it? But also what's the first reset that's ever been found but I. I would suspect that fasting can help but probably it's not enough off to really do what these powerful jeans doing. When we'll figure it out so fasting I still do that as much as I can? For one main reason and that is is that it's going to activate these defenses that at least slow down and somewhat stabilize the EPA genome. Decay that we call And but we probably league or something more potent to really go back twenty years but do we do we slow down aging By fasting and running absolutely no question. Yeah where I mean affecting these pathways the amp as the cer- tunes tour and then I jeff one insulin signaling all those aging pathways certainly are affected by by fasting caloric restriction. But wh what's good about those pathways is that they seem to really safe relatively safe. So metformin foreman is being tested in millions of people in a D boosters obtaining mice for many years now and in some humans for a while even clinical trials that. I'm helping helping to run. So that's good but on on the the more potent age reversal. What we call EPA genetic resetting now? We're playing with fire because we're really sending cells back decades and if you do it too much wind up turning a mouse into a giant tumor which is not what. We're never going to do that to a human so we need to find ways to make this new very potent effect safe so you could theoretically come to my lab and I could inject you with this stuff and you could take doxycycline and turn it on for as long as you wanted. And that's all theoretical but went crazy. When I'm going to do that? We probably need another few years of clinical testing before I can say that this is going to be usable in a wider context. But if you're wondering why are we testing the is protesting glaucoma or blindness old mice. Because that's already on the market For Av so viral us and it's localized so if there's any problem it's not it can hurt the rest of the Wadi Anyway wasn't yeah. Wasn't there a clinical study Japan. Maybe it was where they used into split on stem cells. Too late. He'll some some. I don't remember if it was like macular degeneration or some other retinal problem. It was some kind of blunt former blindness thing I think I remember reading that that study. But just kind of go back where you were saying about the epidemic clock and the aging and I'd always wondered about with the you know the these these transcription factors that are able to sort of take already differentiated cell like a skin cell or neuron or a liver cell and turn it back into a a a stem cell pluripotent stem cell You know I always wondered. What about the EPA Janine genome right is it like? Do you have an older EPI genome. But you're like somehow you know like you actually reset the EPA gentleman. That's how it works. Yeah so I think I think of the genome him as the digital information so this Zeros and ones or in this case. At but all the EPA genome is the reader of that and it's analog and it's very hard to maintain over eighteen. It's a loss of information to be. Yeah Yeah but how do you get back that information. So I'M GONNA I'm GonNa Geek out a little bit because your audience is the smart one tobacconist in one thousand nine hundred eighty eight. There's a the was a man a brilliant person called Claude Shannon was an mit and he wrote a theory mathematical theory on communication and his goal all was to correct the loss of noise during transmission of a radio signal during World War Two and beyond and he came up with mathematical theorem. Of How do you make sure that the signal that starts here is pristine when it gets to the actual receiver and what he decided was you can either make it digital or you can have somebody who's observing the signal and then if it gets messed up you then send a replacement signal We now call all that. TCP Ip it runs the Internet. That's how it will work. That's why it works. And we wouldn't have an internet if it wasn't for Claude Shannon's work back in the thirties and forties. I think that's it's a good recipe for understanding why we age loss of noise over time analog systems very prone to noise but that system of resetting aging how how do you get the original information back that it was when the signal was percent. That's what we're working on. That's what we think the fact is able to do. They are the the group that sits above and says is oh that signal is degraded us that signal. Yeah that's cool. Well that's all pie from. I think that that I've been writing a book which is coming out later this year in September and so I've been so busy writing book. Haven't even put this out in scientific right right so it may be one of those times. Scientists puts his whole ideas and theories in a book before it comes up in peer review. So we'll say right But you know I think it's it's there for people to to judge Maybe by September we'll have some scientific papers written up as well. What an exciting field do you think? Other scientists in the aging. Philo start working on this. I feel like this needs to be there. needs to be a big push lake thing. You're so right now. I mentioned one. Call US Beaumont in salt. He's the pioneer Steve is part of our Dream Team. there's another guy virtually guys currently but hopefully not forever is is My Most Serrano. He's been working on his in Spain. Barcelona he's been putting these factors into mice but there aren't just men working on the EPA genome Beijing so a couple of really top leaders also and Brune as at Stanford she's been working on the EPA Jimmy Causes of aging And we have Shelly Berger. UPN WHO's been studying among other things. What makes the difference between a short lived at and along lived at same genome? Just different EPA genomes and Jessica Catala works on the epigenetics of east cells and try to work out exactly what I was describing earlier about the distribution of proteins between Dina breaks and controlling thing a cells age. And so though that's it that's basically the world's elite teams of epigenetics of aging but it's exploiting Two three years from now we'll have hundreds of lives. Yeah sounds I mean this is cool. It's something I've definitely this. This whole idea like is definitely in in some way. Come to my mind with the the Yamanaka factor and using that to like a reset for aging. Not just about making. I mean there's always the the okay well you can keep replenishing your your cell types types in different organs and kind of keep it going but like to like turn it back to think. It's a young cell. There's gotta be a way to be away right. Yemen did us a big favor. Actually John Gordon who won the Nobel Prize with Yamanaka. He really told US years ago. Back in the nineteen eighties that that reversal of aging is possible. And we didn't really get it. What he did was he took an adult cell nucleus from Tadpole put it into a frog's egg and made a new type whole what that actually tells you is that your genome can be reset to go way back? Aging is not a one way street. Yeah the fact so you can take your adult song. Reset to stem. Cells is proof right and we and now we know the machinery at least the beginnings of it and it's very exciting time so excited right now like. Yeah there's all this other stuff we were going to talk about. You know we you mentioned boosters and we probably should should definitely get into that but well this central to because as I mentioned the proteins many of them are moving around controlling the EPA genome. You want to stabilize that is best you can animals like whales and naked mole. Rats have a very stable able EPA genome so this moving around routines and EPA. Genomic noise accumulating if we're exercising we're taking ad boosters we do slow that process down. I believe believe. Let's talk about. What boosters are so the precursors for the issue making eighty in our bodies and we? Yeah we do. And so eight is recycled in the body. Because there's grams of Econ eight that much easily. And there's a psychological the salvage pathway van de and it all starts with nicotinamide which is a a form of vitamin B. Three. But you can't just or you can but it's not very effective just overdose on vitamin B.. Three because you need other things to make the big molecule. NADC is the reasons called nicotinamide. Adnan dynamically tide. Is that Scott. These three main components and the dynamically tide is related to DNA online right. But that's beside the point. It's a big molecule. So that if you give a big molecule to sells it doesn't get taken up so we don't feed animals in D. and we don't just feed them nicotinamide which is the little end pot of eighty. 'cause it's too small in the UK these other parts so any man and in our two molecules it stands for Nicotinamide Mono nuclear tied which is essentially the precursor the immediate precursor to eighty eighty. If you give a cell in it will be taken up by transporter which was just discovered by my buddies keenum I used to work at. Mit Now he's at washy. Few weeks ago He wrote about it. I wrote about it that There's a transporter that sucks up intimate and the man is converted within one step to eighty in the cell. And now it's locked big big. Marcus locked inside. The cell and that step is carried out by an enzyme. It's got a name called an empty and that ends on goes up distress and calorie restriction in yeast. It's the same step. And so we show years ago that that step of conversion of an amendment and a D. or in yeast What is it Nicotinic? Acid into an eighty is critical. Step for boosting. Ad When you're going through your circadian rhythms when you exercise when your cells stressed and without Out that step you. Don't get the benefits cal restriction your organs. Start to get old. So what is in our so in ours Fairly popular a lot of people have heard of it sands nicotinamide nicotinamide Rabo side. And all it is. It's just a smaller version of anime in without a phosphate on there so there's phosphorous on it. I'm so if you've taken are your body has to I put on a false first and then it has to Basically linked to them together to make the do so with all that said and our gets converted into animation first and then into NATO. Yes yes it has to yeah But in our and and and have both been shown to raise the levels in animals and in humans as well and small nuances about the differences but they both seem to be effective Not just in humans. Actually I should say in mice orbiting yeast. They work as well which is nice I suppose people are interested in the plant world. And what we eat the same pathways. These tune pathways exist in plants as well and they get turned on In response to stress we call this Zeno Hamas the idea that when we eat stress plants we get those molecules. They help help bodies so resveratrol back to that old chestnut. It's a great molecule that is produced when the grapes get stressed and fungus a the fungus will stimulate it or like of water so the when they've harvest red wine they don't they hope for a dry season that will boost the virtual levels and although although good good polyphenol molecules and we think that I think that When you ingest those molecules the tunes are have evolved to sense the plant world and if your food is stressed out your body will hunker down and become fitter as a result of sensing that because we can see crops that are dying or if the water tables drying growing up? Maybe contestants that little animals that we evolved from or even you know Squirrel. It's too dumb to know that it's food. Supplies stressed out. Its body has to take care of that that message. Yes so the spirituals. Activating all these stress response. Pathways that are basically you know in our you know we have in our inner body the and and basically turning on all these genes that are helping them deal with stress. But they're like staying activated for longer and so when you know basically aging which is a stress You're if you're basically dealing with aging better right couldn't put them myself and then the opposite if you spend your whole day sitting or typing or You're always satisfying in your hunger your tunes and your other pathways and economies tour. They say hey times are good. Let's just grow tissue goforth. Multiply Oy and not build sustainable body in the long run and because there's always a trade-off which which Tom Kirkwood call dot the disposable Saima hypothesis houses. And it's very true. You always have your body in a state of a little bit of stress hormone. We call that. Yes people listening to the PODCASTS. Or heard me talk about armies quite a bit my favorite is sulfurophane that molecule and the cruciferous vegetables. But I've been there is virtual field when I I was following it back in early. Two thousands You know is a very skeptical that there would be any affecting humans taking reservatrol very trial because certainly not from drinking glass of wine but From supplementing just because it seemed as though like the doses required to get some really beneficial effects. It's at least in some of the rodent studies seem sort of you know high and it wasn't didn't seem very attainable. But as you know this there was a really really Sort of compelling primate study in Rhesus Rhesus monkeys forgot that was published she was like made to thousands or doesn't doesn't eleven or something refer to cubs group at NIH. Yes that's right They they gave these rhesus monkeys Repair trial and I think they start. Start out with the lower dose like eighty milligrams per kilogram went up to like four hundred and eight any reason. Do you know why they start with. I've seen more than one study to that. Yeah so just anecdotally. What roughly told me I think is that They started at the low dose and didn't see a change in pulse. Wave Velocity in the blood vessels. So they up to. And then that's what I sorta benefit. Oh Okay so well this study was you know the the doses were very doable in humans when you convert And and basically they you know feeding these these monkeys feeding Mike this terrible high high gross diet high sucrose on high fat and they like the cause them to have like forty percent increased. Eric Orrick stiffness but the spiritual completely ameliorated so I was like holy crap. That's pretty cool. I think that was the one one study. That sort of changed my view And then I started sort of get into the literature and read morons there has been a variety of clinical studies. Is You know and yeah well well. I'm glad somebody's reading the literature because there was there was a hate me club with resveratrol Because it got so much attention at anything that gets a lot of attention gets the hate me club back in reverse but virtual I still take virtual Probably a Graham also every man really. Yeah in my yogurt. I don't measure it out I just just shake it in so it might be half a gram to grants from your own late stash. It's like us in the basement. it is I'm not they don't really find doses of resveratrol above two hundred fifty milligram. Yes right you made a good point. which is it's it's a really Insoluble molecule and. That's one of the well the two problems with virtual. What is it really insoluble? So if you give it as a dry powder to an animal or humanists less likely to get absorbed we know that as a fact included with a bit of fat it'll go up five to ten fold in the bloodstream. Really big effect. We've seen in mice and monkeys with bit fat in the Diet as well. I'm in the second problem with virtual is that it's light sensitive. And so those people who researches who put it in a plate with worms terms or Didn't treat molecule with respect. He Goes Brown. It goes off. It's one of the reasons. It's very hard to put in a cosmetic because medical turn brown if you use Brownnoser virtual at work you've got to keep it in the dock in the cold and it'll be fine okay so so Debasement cold dark mark and also. I think there's various forms Trans resveratrol. I go for trends because when we gave this form to this or to an enzyme it didn't activate it but the Trans worked brilliantly. Yeah roughly Kaba actually He's been a good friend. Over the years colleague he did the study with else on the mouse. Whereas virtual study that showed that on a high-fat diet those mice for extremely healthy and long lived and their organs? When they opened up the mice there were pristine? The mice was still obese. Because we didn't give him a lot of virtual is pretty low dose but their organs were so beautiful Their arteries when you stain them for oil fat it was night and day. The ones on reservatrol will the ones without reversal staying with fatty lumps reversal. Clean Clean and that alone makes me say you know revert. trolls probably not GonNa hurt me and It may very well help cut. INVESCO system seems to be really important for cardiovascular the vascular system like and I'm just kind of want to know why why is it we we have a number of ideas and virtual is a dirty molecule. So there's not just one way it works works So to definitely involved we now have announced that's mutant for the rest virtual activation of one. So we now see that some some aspects like endurance convertibles seemed to be through certain so one of the effects is through sort was anti inflammatory actions in the lining of of the blood vessels. The into the'll cells. How yeah that seems to be important? And there's other aspects also in Dina repair as well infiltration of macrophages in there seems to beat dampened and we also looked at oxidative stress in those arteries of those mice treated and it was way down and there was virtual nice yeah with the rhesus monkeys. With you you know basically like you know completely reversing that. Forty percent or stiffness. That's like pretty pretty dramatic effect is it is and so so yeah. I think it's people always a true is not sixty minutes to the story. And then there was an argument about how it was working and so people have confused about the molecule. I still stand by it because the results like say animals and thorough clinical studies. Now let's that are really positive in humans. Not all of them sometimes. It has no effect those one study study where it interfered with Endurance Exercise Yeah don't understand that but form it was Kinda showing disarming similar where prevented my conversations automations. Yeah I mean maybe run. What's maybe happening is that if you're dampening antioxidant free radicals too much intellectually losing that in fact exactly the modern premisses but but I haven't seen any downside? I'm you know I'm I'm a one as you'd say clinical trial I've had my heart checked checked out with a three D. movie. MRI by heart looks like it's twenty. It's got no sign of aging so it's doesn't seem to be doing myself and my dad any harm arm. So how long have you been taking it. Oh Jeez since two thousand and three wow you take battleground day. Yeah that is a couple of study As you know the there was a couple. There's face one into clinical studies on Alzheimer's disease where they were given five hundred milligrams or thousand milligrams of risk jared reservatrol trawled both. These studies Found that there was a reduction in amyloid Beta forty two and cerebral spinal fluid. There was an improvement in cognitive function. Shen and a couple of other parameters so. It was kind of interesting because I recently had Dr Delbra Edison On the PODCAST. And he has this whole protocol where he's able to with certain Diet and lifestyle factors you know improve condo function and also by Mariah like help shown to like reverse some of the Atrophy in the campus so reservatrol was on his. He's got this long list. I kind of like everything in the kitchen. Seeing where I was like jeeze like what is all very trial was on there. I never really knew why until very recently was reading a little bit of the clinical studies. I thought that was super interesting as well And and then the other thing. That was interesting. As you know is the toughest because seems to be activating toffee and I I also interviewed Guido Chrome on the PODCAST. You did and he talks about the is three signals that are important for autophagy and one of them is the a decrease in protein assimilation. Yeah because there are two ends are histone deacetylases right so that would lead to a decrease in. That's exactly right. So that's how these pacmans a working and one of the enzymes that they work on is a an tougher g-protein that goes and destroys bad protein. So it's perfectly reasonable to think that if you take resveratrol it might be clearing the body. I have seen the study with with reservations. That's yeah Richard Turner are. He's that's the study I think you're referring to look really promising. And he did what looked like a very convincing study but He actually elise still trying to raise the money to do his lodger trial. And I'm trying to help him with that. But I would love to see that repeated in more people. Yeah I know that Dr Cromer has published study looking at biomarkers of tough gene humans after After been fasted and I think one of the one of those was looking at Lake Lies Distillation on licensing or something so It's not working so that's all very interesting The boosters also helped the brain so at least in mice Couple of labs have published published now in top journals like sell that raising levels in the brain also improves memory and slows down the advancement of Alzheimer's in mice admittedly I know we've cured Alzheimer's in mice they'll both nicotinamide riboside and nicotinamide mononucleosis have been shown to do that in animal studies right. Yeah you've been amazed yes you uh so that that's true. I would love to human study. Actually one of the benefits that we might see is also improved blood flow and that might be helpful for vascular dementia. Because as I'm sure you know we've shown that an and others have shown that it also helps blood flow in and actually mimic exercise and regrow the vascular system. And we've done that for muscle We've got some early results that it also helped restore blood flow in the brain which is badly needed for a lot of elderly people right. Yeah that's a that's a big. I mean that's a big thing to function So animation was able to do that in mice. Yeah that's So with that with the clinical studies. You know there's I've seen a couple with my right side but I guess the you know the the question is what the Nicotinamide Rivaz. There's been a little confusion about like you know whether or not nicotinamide riders sides. You've been really getting an inside cells in different Oregon's other than the liver This was this was this deflects paper That was done by Rabbo win it's Rabinowitz. Rabinowitz thank you Yes that that study. He recently published in just a few months ago on looking at nicotinamide right beside and how orally at a dose half of what typically is used in all the other. Nick Tim my right side. Animal studies so typically they do four hundred milligrams per kilogram body weight per day. I don't remember how long duration they were doing but any deflects study did two hundred milligrams per kilogram body weight which is significantly less than what all these other studies like. The one you mentioned with Alzheimer's Disease and other studies that have shown improvements in Mighty conroe function in Mighty Contra mediator mice and and also muscular dystrophy and all that we use double that does. So maybe you know the the this Any flex study that showed nicotinamide rivals given orally really didn't form an ad muscle but it didn't deliver could have been a dose dependent thing it would make sense because we we've done a lot of this in mice and now in humans and there's a threshold that you need to cross need to take certain amount to to get over probably the bodies clearance mechanisms And then you get up to a level that plateaus after about nine on days and they may have just been under that threshold so the body was just clearing it out but you have to seemingly over well met clear out system. So that's why we do at least four one hundred on meeks peculiar and that's why I'm making my right beside the question is I mean that's like if you talk about human equivalent doses for like one hundred eighty pound man. That's like over two grams a day. And it kind of leads me to my next question which was The most recent clinical study with nicotinamide. riboside where they actually used a much higher dose than the original study that was done with Basis the him that had terrorist in this dose was like a thousand milligrams a day and they looked at a variety of end points in addition into guide endurance. Look Diet Drugs. You'll study yes. And and there's no statistical significance in anything it raised energy levels but there is no oh statistical significance series trending improvement in the vascular system and There's but there was no effect on endurance and I'm wondering again well if we're if we go back to the human equivalent does what was given to the animals that was still less than half I mean so the question becomes is it not even making any in the muscle tissue at the dose or you know so which brings me to the NICOTINAMIDE monetary? A tired you know like now that those studies have been done in animals at a much lower dose Then four hundred rounds. They have Yes we in my eleven and at the company Metro Biotech. We've been using Whole variety different different molecules in different What's pharmacokinetics says a lot of literature? That I could. I could talk for another hour on one of the big questions people asked me. Have you ever put an animal head to head in a study and we need to do a lot more of those Typically they're not done and I'm unaware of it being done in humans at this point but in mice what we see and for all in our folks out there. Please don't be angry this is this is just data. I don't run the experiments I just deliver the message that at at the same dose will increase endurance. And I feel what that does. It might've been two hundred or two hundred fifty and amend didn't increase in during Asari in our did not increase endurance but Edmund did Do find that for some parameters and cable line who I mentioned earlier who he works on dog aging Ching now after doing so to extension lifespan. So Matt also has published that Comparing an iron men only work in his his disease these model which was a mighty convert disease where those animals really need a boost of ad so one of the issues could be that An amend is better molecule so in that regard it could be that maybe the mice just work better than humans and we need a bigger dose. But what I'm working on which is not talked about a lot because it's in the commercial realm is. There's been a team of seven chemists working on much better molecules than any of these two that I'm talking about Super ad boosters and we have ones that work better than men and these time release these are local pro drugs and those are the ones that I'm really excited added about for medicines at the future. That don't just increase. Someone's endurance could actually treat diabetes and heart disease cancer. Alzheimer's that said we are doing a clinical trial right now with a molecule called sixty-six Am I B is just metro biotech. And that's a couple of clinical trials that are being done at Brigham and Women's Hospital in Boston Separate Group for me. It's all independent. That's just a safety study so When I come back to show if I come back on your show I may be able to tell you if we see some actual efficacy some results? We're GONNA be looking in the phase two study at strength and endurance in the in the the muscle of people after some men dosing. So we're on the verge of knowing if this is real oh not for people. Is this the first animated study. That's being done in humans clincal. Let's say that you're doing here is We've done a couple but as far as I'm aware where the only ones that. Actually you remind me to say something important for the listeners. Make sure your your and our uranium and is kept in the cold If it's just on the shelf and it's not in a stabilized form then it will degrade into nicotinamide which is something you don't WanNa take doses off. Because we showed in my lab. Many years ago that nicotinamide will inhibit the tunes and pop as well and and interfere with DNA repair. What don't really like the like the form that's in vitamins right? It doesn't have a super long shelf life That's not very well known so. Okay cool. Freezer Fridge. But I mean like if you're buying if you're buying nicotinamide arrive aside from a variety of companies that make it. It's certainly not shipped to you cold so the question is how much of. It's already degraded just on the shelf. I don't know I mean it's kind of a case with probiotics you when you get probiotics you want them. Let me ship to you cold. So that their live Right same thing here We we have to also replace our mouse in amend. We put it in their award. We replaced that every week because it goes off but that if it gets wet or gets a bit of humidity in the bottle It it's a a short time before it's grading and we're talking a little bit before the before we the podcast about I was super excited. I think it was the two thousand sixteen cell paper. You mentioned the group That publish the basically that was given to normal mice Cina my study my study. That's right And and basically I think it was about two hundred milligrams per day like that that dose because I remember looking at the dose going. This is significantly lower than nick. My dose US and It it it seemed to delay tissue aging and multiple organs. where it was like? I don't know did it. Extend my span. He didn't take it long enough he ran out of material and in those days was hard to get and was very expensive. It's still is very expensive. We're still paying tens of thousands per kilo But what he showed was that over a year of treatment Pretty much all the parameters of health in these mice were were improved. An if those mys- didn't live longer I'd be surprised. But we have done in life span in my lab and it's still ongoing and it's been crowd source funded so thank you for your donations But it already. It looks significantly. Different the group that's on demand In their water supply and also it improves. Frailty in other words. They're they're less. Frail looks like improved heart function as well The dose A CON exactly remember we using It's probably around four hundred. which is what South Standard Dose? But don't quote me but yeah I am in an arson to do remarkable things to rodents but like you say like you brought up the challenges a does it work in humans and be if it does what doses necessary to get was effects right. And it's going to be side effects with Like if you read the the most recent study the clinical study where that but the dose of Nicotinamide Roberson was a thousand milligrams. There were a lot of people that dropped out because they had rashes. And uh-huh yeah there's some side effects there were since I might be within our. We've never seen anything like that within a man and I take Grandma Veneman every morning. So the A and is the reason why they're more studies with our Because an expensive yeah well. Historically some companies started making in our early on and made it widely available and cheap to researches in fact so cheap L. giving it away to research so it became used much more often and then animated increasingly and if any scientist lab once abandoned me. No I'm happy to subsidize it if they'd like But yeah an enemy was late eight on the scene because it was harder to synthesize. Because it's a big molecule needs at phosphate and I bet chemistry quite difficult. What are so? You're you mentioned the company That you're is this the company that is trying to get a supplement set up or is this like so I I don't do supplements since And I don't endorse products. You can only do one. It doesn't work for both. I've committed my career to making pharmaceuticals that are proven to work And a proven safe and awarded You know saw by the FDA. It's a it's a drug it's a drug and and that's because I in my early in my career I dabbled in in the supplement world with virtual and only lost it about three weeks before I had to get out because of it's just it's incompatible with for me at least Me To be able to without getting criticized. This is what I think. This is the data and I want to be able to say that without making any money off of it But also I find that the supplement world is it so controversial and not just that I was scared away It's a sad thing that I am unable to talk about supplements by name Because I obviously know bit But I just can't because I've I've already been dragged into lawsuits. I've lost a lot of money by that. I've done nothing wrong. zipped open my mouth And there are a lot of companies out there who have a lot of money who don't want want me to say things So unfortunately I really am unable to do that. I do tweet out on social media where I can. I've written blogs about it I'm probably one of the few scientists that tells the world what I do personally And use myself as a role model for people to judge but I never recommend anything because first of all. I'm I'm not a physician. I'm just a scientist and mostly study my so. I don't really know yet how this is all going to play out in people. It'd be nice to see if men could be Available without a prescription now would also be nice if someone like me did a clinical trial so we knew what would happen those details. Well that would be. That's the first awesome foremost. I mean knowing the Dosa take. That's actually has an effect right. It's not just like yeah I mean. Don't take some gear x amount just because it makes you feel good good. I mean placebo does something. It definitely is changing dopamine immune system and stuff but I agree. Yeah so you mentioned supplements you take a gram of for spiritual fair. Trou- sorry yeah. Graham is reserved for whatever I pour it into my urine about a gram of in and that's also when you know not I could just take that as a captial in the morning Down with a cup of coffee. And that's a pretty big boost I find logically Those three things with caffeine gene included You can ask my friends. Sometimes I have to temper it a little. 'cause I'm like a a a mouse on oxygen running around the cage a little bit too much but It works for me. It helps with. I believe it helps me with jet lag as well or lack of sleep. I've got three kids so sometimes sleep. Well I know you have a young one so you know. That's it's like I'm starting to sleep while now but sleep is really important for aging as well I'm Particularly the aging brain. You know so. In fact I was wearing a continuous glucose monitor. I've been wearing one for a few months now and My son like around Thanksgiving time started having teething and stuff and he started waking up in the middle of the night. And it'd be up for like an hour and it was like so I was basically having very fragmented sleep and My my blood. Ugly Coast levels like my fasting glucose levels and my post-prandial were like fifteen twenty units higher. And this was like repeatable Very sorry I was. You know my Diet's pretty much you know. Eat the same thing so it's not. I wasn't eating anything like a cookie or anything like that. I mean it was just like and doing some high uneatable turning did help. And they're actually some research on that but I was astounded by the effects leap pad or lack of sleep. Yeah if you take a rat into private of sleep it'll we'll get diabetes within a matter of a month so I mean it's just like it was I'd read the studies I had a Dr Matt Walker on the podcast talked all about it but when it happens yourself and you see the data I mean. Of course. It's still just one for me. I mean it was just like it was very to me and made eight very real well. It's like this really is regulating my insulin level my insulin sensitivity. I could see my age changing when I had young kids. Oh absolutely I've aged for sure I mean you can see like the especially as a nursing mother and you're in the early days of my son being born it wishes. It's just so hard I mean I mean. It was so check out photos of me in my thirties. Early forties when it was lack of sleep and stress and my wife Screaming at me for travelling that kind of stuff that warming out you can see. They're aged rapidly since then I don't think and others don't think that I've engaged much since then so it's sleep and stress all do you. How much do you sleep at night? we'll often. I'm working up until eleven. Eleven o'clock which is a bad habit But I have found ways to get to sleep pretty quickly Avoiding Blue Light. So I wear those yellowish clauses What do I do occasionally take nibble of asleep So you can feel occasionally when I really have trouble sleeping because I used to be an insomniac but what I found is is the doses that they prescribed for some of these medicines. I I won't say which but Way More than I need at least and so I just nibble on it. And it's enough to get me to calm down and I go to sleep And then in the morning get my boost. I'm going again but I typically get seven hours sleep and if I didn't get more than that if I get less than that I'm I'm I'm in trouble because my brain needs to be going one hundred miles an hour every day. Yeah have you ever heard of the Phillips you lights Phillips here is really liked. They make these lights We have them around our house. That The you can program your phone. And they turn red at a certain hour so like ours go read it sunset and so there's no blue light coming and it's really like you don't have to think about it. It's really makes a difference and developing children are really sensitive to light like even more sensitive than adults so like all notice if we're travelling and hotel room or if we're busy visiting like my in laws in the state and they have they have lights on at night that my I son. It's like it's harder to get into bed and it's it's very obvious mom and so I'm always like freaking out trying to turn off the lights and leg. WE'RE GOING TO BE THE DR. I took my kids and I three of us for the three of us. We got My wife Christmas one of these indoor Plant plant growth Hydroponics and the light for that hydroponic unit. It's about a foot long. Maybe two feet. It's super bright and it's in the kitchen and it was so bright that I was finding I couldn't sleep because it also comes on at night and it's just as intense light so we've had to move it to the dining room and drape clothing over short because otherwise I wasn't like hotel rooms with the alarm clock. It's like blue lights like it's like letting lighting up the room you know I'm like always throwing stuff we've gotta happen happened filter and there's like this right bread light. I mean I'm just like who is designing stuff. You don't want light when you're trying to sleep and I'm with you in my bedroom L. Bedroom we've got lights popping up everything glowing now and they like to put blue lights in these things now trendy. Does anyone think now. Yeah I know anyways. That's whole other topic super excited about all your research The the EPA genetic clock stuff has super pumped Gut David. We'll have to stay in touch. I mean in super. That sounds good. It's an understatement. How excited I'm like I? Definitely WanNA talk to Steve. I want to get in touch with him as well But Yeah Yeah This is like yeah so that the people I mentioned. So Steve Horvath Manuel Serrano. In one Carlos Belmonte have just formed an entity. ought to fund research in this area and to go into human clinical trials probably in Coloma which is a disease? That's extremely a hard to treat. You cannot reverse the damage that's been done and we think we might be able to so it's exciting times The research is going extremely fast. Makes my head spin. I get takes every day of breakthroughs bruce which is a great privilege But Yeah I'd love to come back until you more I. I tweet out some results. These days they used to be very tightly but now it's too exciting. I'm not to tell people about it as we discover right Totally I'm following you on twitter as so. That's definitely if people wanna find you on twitter. Twitter twitter handle is at David Sinclair at David. A Sinclair pay for Andrew. Eight hundred and you have a website website. A book coming out. Well we have a lab website will shortly launch a book website where they'll be information build a community around the book. The book comes out in September. It's an unusual book. It's illustrated by one of America's greatest talons for medical illustration Katie Delfi. And so that speckled in there. And we've got a cost of characters in the air that range from Captain Philip Philip who founded Sydney Colony. who used to hang not in my backyard in Sydney two hundred years before all the way through to Scientists in London who will make major discoveries led us to today and then it projects forward in what with me having a front row seat on this field both in the biology and industry. What does the future look like? What does it look like? If we don't succeed which which is pretty bad. What does it look like? You've wildest dreams come true what's that will look like for us and our descendants. Maybe we get to see this. Definitely I I I'm looking forward to the book for sure Thank you for connecting with me big fan of your research for quite some time and I'm even more excited now about all the new stuff going on. I had no idea I mean you just start talking about it and was like yes I think so. It's it's really great to be able to talk about it with someone who literally knows as much as Oh i do about the topic. That's flattering. Thanks thanks thanks so much for listening in on this great conversation but as many of view may know listening is only half of the actual presentation when it comes to an episode like this one without watching the video you miss out on. The graphical figures quotes from the studies Saudis definitions of technical terms and other onscreen assets. That help provide context for these sometimes very technical conversations. What you need dear? Your listener is the cliff notes version where you can see exactly what you missed. In other words you need some kind of way to tap into that without re watching the whole episode. Ain't nobody got time for that. That cliff notes version is real and it's exactly one of the benefits we now offer foundmyfitness premium members. Not Not only. Can you quickly flip through the over one hundred fifty amazingly helpful presentation slides at a company this video but you can also gain access to the brand new members only podcast. Yeah speed with special content access to the new monthly QNA series get in on the so-called members library where I keep my background fact sheets which are my private of it notes. That is synthesized just to get up to speed on topics prior to my conversation with experts in the field like Dr Sinclair. You also get access to my brand new bimonthly I'm monthly Science Digest newsletter just for members which is an

EPA nicotinamide NASD Sir Tunes Dr David Sinclair Terry Steve Mit premature aging Shinya Yamanaka Andy Cells Steve Horvath Nobel Prize Dylan professor cer DNA damage
Wondery Presents Life is Short with Justin Long

Foodgod : OMFG

07:35 min | 1 year ago

Wondery Presents Life is Short with Justin Long

"Justin long this guy's renowned out there. He's been making audiences laugh for decades. I was spending years in the has of characters. He is ready to peak inside the mind. Some the world's most entertaining an interesting people out there now on the podcast. Life is short with Justin Long. He has his famous friends about how they make the most of their time. Even at the clock seems to be running faster and faster these days justice digs in some of the most important questions in his guest. Live is like. Hey what's your favorite Emoji. And with his brother question by size and he modest of mine about them very embarrassing and fun stories. Just long delivery side-splitting labs every week on life is short now. Here is a preview of the store with Justin Long now honest episode Justin Chatwin Kristen Bell South with a good place frozen. Now while you're listening makes you hit subscribe button to life is show adjusted long and other great ones shows on apple podcasts. spotify uh-huh rather you're listening right now. Just guess what guys life is short. Go subscribe now. You raised very Catholic. Yeah Catholic High School. Yes fast growing and you were practising. Your parents are still well. My Dad's side of the family are a little more. Chester's you know Christmas and Easter. Yeah that's what we called the Chester's But at my mom is much more religious and she's a little bit more born again And I went to Catholic high school and Never questioned it because you weren't really taught to question anything Which is fine? Some people don't need to question Russian. It works very well for some people. It wasn't working for me because I didn't love then going to New York when I was eighteen and seeing All my gave friends and wondering how that fit in and I was like some of these things seem very not nice to me this. Maybe this isn't for me I remember being struck by that to like find having having really good gay friends like really like falling in love with with gay people and I couldn't reconcile that that was just felt. Yeah well that's also why we didn't get married until gay marriage was legal because it's right in it wasn't meant to be any grand statement. We talk about it now because if it can be an example of standing up for yourself I love that but at that time it was simply like okay if we have a wedding and fifty percent of our friends are gay. Isn't that a little bit like having a party at the front of the bus is rude. Like isn't what we can do. Yeah it's just felt also gross get married. It's song rose and I was like no. We're not getting married. This feels gnarly. Let's just Wayne. Let's not take advantage of vet until our friends can. It's the antithesis of what a wedding should be which is like bringing everyone together and like unifying and accept the gays. Yeah rules apparently Lazio travels rifling through her not rifling. Yeah slowly gently going through loss on the spray. A little bit of Nicotinamide Lena my mouth. No what is that trying to try this under your tongue and then leave it there for thirty seconds. I know it'll hit you hard. This one's a bit strong but it is the best delivery system Holy Shit because listen I. Do you know what it's around the house I have no devices. I don't do anything never tried drugs and I'm like I want to try. This started being real bad but there is actually. There are a lot of studies. What is that link nicotine to like really tinguely mouthwash link gross cigarette after no? So what would that kind of Bernie's cigarette cigarette Ernie. Yeah but in a hot minty way. I don't get that but there's some there's nicotine is actually really fine and is linked to very positive brain studies and sort of like caffeine is and again. I'm a doctor so but it's the delivery. Every systems are terrible. Tobacco's terrible smoke is terrible decks must have been a dip guys. He always says he's always back and forth on which is really hard. Yeah he's always. It just seems like it's suits him so I mean I don't want to encourage it but he seems yet suits. Yeah well he's very he. I'm lucky he has all teeth. I mean it's a that's his vibe. But he the The only do it was really really stressed. And he's very good about quitting And thankfully for the other nicotine because I don't think nicotine is something I can take it or leave it you know I did. Dip though did not terrible because I have Stockholm Syndrome and we were yeah. I just love the way you in mid dip though for about a year and a half and it was so gross. Our friends kept telling us how gross it was rogers inches. I can imagine I can't imagine doing it. I can't imagine you do. It's like a huge piece of chew in there so we were probably we were in our late twenties and and we he adjusts he got back from another. USO Tour to do comedy for the troops beat the MSCI. Yes he loves doing he always comes back dipping and we were in the car and he was driving and he wasn't looking at me and I kinda like slid it over from the driver's side Armrest and I opened it up and I always say I always like the way it smells. It smells good and barbecue which I think because I've never eaten meat. That is a very like exotic attic sent to move. I stopped eleven. Holy Shit so I. That's a very that's a sent an taste thing that I don't get a little tabby little forbidden fruit totally so he's driving. I put it in my mouth. No He never would have let me and I'm what are you doing. Yeah and he looks over and he's like what are you doing. It and I was like I just wanted to try it and I immediately loved it. I hated that I loved it but I immediately really loved it. Can you believe that alcohol. But Somehow we try dip and I loved it. You must love this stuff then I we dipped for like a year and a half half. Did he like you. Were into thing that you could share together sort of. I think it made him feel less guilty. Our friends that we were disgusting because there were like bottles of dip- like on our end tables and stuff thing that guys do lightly slapped on the end it was gnarly and that must've been better making out though. Yeah was well. We usually spend it out before we made in your mouth but like you must be able to tasted I liked it because I think I like Tim and there was again. This exotic something exotic about it so then after about a year and a half something happened and I think he said to me like look we. We were thinking about having kids. We can't like we can't like be parents who did like we can't that we gotta get our shit straight right. Yeah and he was like Doc. I don't know if I'm going to be able to quit if you don't quit and I was like great. Let's let's do it. And then so he bought like the nicotine gum or something and then we started it off that and then over the past ten years I like many years. I didn't do it and then sometimes I'll see the little nicorettes on the table and I'll grab one of so. That's what drought. I wish I could see you during that period. There's pictures so gnarly.

nicotine Justin Long Catholic High School Justin Emoji New York apple Justin Chatwin Chester Lazio Nicotinamide Tim Bernie Tobacco caffeine Kristen Bell South
NMN - The Epigenetic B-Vitamin for Smarter Genes

Limitless Mindset

51:43 min | 1 year ago

NMN - The Epigenetic B-Vitamin for Smarter Genes

"This is Jonathan with limitless mindset. And this podcast is on the the game changing anti aging molecule nicotinamide mono nuclear tied. I'm going to be calling it. And and M N four short. Now that is an m n not EMINEM's. That's something very different and definitely definitely not an anti aging bollock. You'll that you'd want anywhere close to your biology and you are going to want to check throughout the article that goes along with this podcast. You'll find it linked below wherever you are listening to this as the article article is going to be kept up to date with the exciting scientific research that is being done on this bad boy and I am going to also encourage you to share this podcast give it a like give it a thumbs up give it whatever ever sort of signal you can that is going to boost it just a bit in the algorithms that rule the distribution distribution and visibility of the sorts of MP threes because this is a really cool bio hack. I really I think this is one of these things that more people should know about that. More people should have in their bio hacker cabinet. And you are going to listen to this podcast in full at the end I'm going to discuss a fascinating Connection that I made between this molecule and a really interesting book on mindset that and shall we say manifestation that I read recently so so is a B.. Vitamin Derivative it is the most direct and effective way to supplement. The game changing anti-aging agent in eighty plus. You've probably heard of that. I rake an among carbon sixtee- St but minister fullerenes and S K Q one as a game changing anti-aging innovation quote any. We will turn out to be one of the greatest advances in medical science. Since flemming invented penicillin proclaimed Dr Dr Phillip Milligram of the any D- Treatment Center in San Diego California. This podcast is mostly going into focus on decoding. The Human Studies and the animal research out there is saying about nicotinamide Mono nucleotides along with any plus and how the squares up with the anecdotal experiences of bio hackers online for more of my own personal experiences thoughts and comparisons. You're going to want to see be sidebar of the meta-analysis article for this again. It's linked below. That's where I'm going to be doing. Reviews reviews of this product in supplemental form. Let's talk about the scientific research. There are over a hundred hundred papers about an and thirty four items of human research with an active interest in the compound by anti aging researchers. If you're clever with pubmed you might not that. Currently there are no completed an M. I'm an clinical trials with humans. There are however twenty five n d plus clinical trials which is what n n metabolize prices into so. We'll be considering the human data coming out of these trials. Currently there's at least one and a human trial going on in Japan when it's published in two thousand nineteen or twenty twenty we'll have a wealth of clinical data by which to further evaluate. An Colorado. Universities collaborated on a twenty nineteen clinical trial trial which recognized N N and N R supplementation is well tolerated and elevates in eighty plus quote. Put the use of any plus precursors to augment plus bioavailability has been proposed as a strategy DR A G for improving cardiovascular and other physiological functions with aging in humans. Here we provide the evidence In a two by six week randomized double blind placebo controlled crossover clinical trial that chronic supplementation with the any plus precursor vitamin and our is well tolerated and effectively stimulates eighty plus metabolism in healthy middle aged and older adults and I linked to a short video featuring David Sinclair which you're gonNA WANNA watch. He is the godfather of any D. Research and he breaks down its mechanism. Let's delve into its history. Articulate article appeared in scientific American entitled Beyond Resveratrol the Anti Aging among any D- Fat. And it's worth quoting here. The story took off toward the end of of twenty thirteen with a high profile. Paper by Harvard's David Sinclair and colleagues sinclair recall achieved tame in the mid two thousand for research on yeast and mice. That suggested the red wine ingredient resveratrol mimics anti-aging effects of calorie restriction. This time his lab made headlines by reporting that the Mida Mida Qendra in muscles of elderly mice were restored to a youthful state after just a week of injections with and and is this a b vitamin from space and a man is a form of vitamin women. Beat three Dr. Lino explains in his recent book motto contrary in the Future of medicine which I read back in in two thousand and one NASA scientists found traces of vitamin B. Three in meteorites adding support to the theory that life on earth with seeded by extraterrestrial sources vitamin B.. Threes importance to life is apparent when we consider that it is the precursor of the biological molecules any plus and entity h recently recently more biologically efficient forms of vitamin B.. Three have emerged for example and are currently stands as it's the most efficient precursor of any place and any D. H.. It's important understand that N M N is a by available source of energy plus the more you research and eighty plus the more. You'll think to yourself while this stuff sounds sounds great can I just take it. As a normal supplement the only legitimate way unfortunately to supplement any plus itself itself is via injection which is expensive entails a visit to a doctor and a needle prick to supplement your in eighty plus levels you'll want to orally supplement either and amend or its molecular precursors from A.. Twenty nineteen paper entitled exploration of Diverse Therapeutic applications of a potential molecule published in the Journal bio-molecules which delves further into the uses and the benefits of an quote due to the unavailability of a suitable transporter and M N Inter's inside the Mammalian cell in the form of an are followed by its subsequent conversion to any men and Kennedy plus. This particular molecule has demonstrated several beneficial pharmacological activities in pre clinical studies. Any men could open up new horizons in Modern Therapeutics. This bio molecule has demonstrated did numerous beneficial pharmacological activities in several preclinical disease models including myocardial and cerebral ischemia Kenya neurodegenerative disorders like Alzheimer's disease and diabetes. You might be wondering so if m any limited comes from vitamin B. Three. Why not just take vitamin B.? Three I taking vitamin B.. Three causes an unpleasant skin. Flush which the Therapeutics Application Paper Mentions nicotinic acid and nicotinamide a mind have several disadvantages. In terms of their therapeutic application. Nicotinamide may cause helipad toxicity or flushing around the Internet. You can find different people talking about the the skin flush that the vitamin B.. Three causes for some people. They say it's really not that bad but some people really hate it and this is a feature that does not share verse. Alzheimer's Alzheimer's animal studies indicate promising therapeutic application intriguing Alzheimer's quote N N N N N has shown promising activity in the treatment of Alzheimer's disease as demonstrated by long at all. It has the capacity passively to treat underlying causes of Alzheimer's Disease For example morphological abnormalities of Monaco Andrea decrease in oxygen consumption rates and any D. plus content. This finding confirms the previous studies where an has been proved for its potential therapeutic application in Alzheimer's disease. Furthermore enemy in treatment resulted into significant improvement measured by a decrease in ETIMA neuronal. Death are West content neurological logical inflammation expression of intracellular adhesion molecule one neutral fil infiltration and micro Galil will activate in the affected areas of the brain verse diabetes and obesity. These therapeutic applications have been identified quote has shown potential to be used as a therapeutic for the treatment of diabetes. Insulin resistance is the characteristic feature of type two diabetes which occurs due to oxidative stress augmented inflammatory response impaired Lipid metabolism all of which can be ameliorated by an Edi plus and N. is demonstrated to heavy weight loss effect. It resulted in a four two nine percent decrease in weight and which might not sound like a lot. But you'll want to continue listening and hear about some of the fantastic weight loss case studies. That are coming out of the bio title hacker community quote an M. N. can reduce age associated weight gain in a dose dependent manner supported by a research on mice and M N treatment also improved Metabolic Disorders like glucose intolerance intolerance and reduced paddock citrate. synthase activity similar to that of exercise in light of the above discussion. It it can be inferred that N M N can improve certain metabolic complications associated with obesity verse Aging Animal Research Found that twelve months of N M N dosage reversed. A number of symptoms of I've aging quote aging is a natural human phenomena characterized by down regulated energy production by Maya Qendra ask previously mentioned owing to the depletion of N. eighty plus in multiple organs decreasing entity plus level is associated associated with age related DNA damage being the precursor of any plus N N can provide thieves beneficial effects as well as stated earlier increase in body weight and obesity related related complications like a decrease in energy metabolism and locomotor activity age dependent. Insulin insensitivity tippety and hired triglycerides levels are also associated with aging these conditions were reversed by a twelve hold month. N N N Intervention Verse Addiction. The NASD molecule is recognized by by researchers and practitioners as a powerful therapeutic intervention in addiction treatment. Rehab and healing. There are two books totaling three hundred and eighty pages which praise any plus precursors as power fleet effective addiction treatment about the author of the Book Addiction and the dark night of the soul slash n plus the light of Hope Paula. Norris mistake air is the groundbreaking therapist who pioneered the the development of American protocols four utilizing energy plus to effectively treat addiction with minimal withdrawal Paul symptoms and without substituting another narcotic the founder of Springfield Wellness Center. She has helped the of people successfully. Break the Rehab relapse cycle from the second book which is ten days is to recovery N.. Ad Intravenous treatment a breakthrough treatment for addiction. Depression and anxiety quote vote N.. Eighty IV therapy has been found to safely bring about measurable improvement in a ten day day period of treatment. The treatment is safe natural holistic and an effective means of helping. The patient began the road to recovery. Three years of substance abuse and stress any D levels are depleted which leads to poor cellular function especially in the brain resulting in brain fog which often prevents effective recovery. We have treated several patients addicted to alcohol hall. Heroin opioids Methadone suboxone antidepressants and Benzodiazepines. Brand names such as valium. The Laura as a pam virtually every patient we have treated previously tried other means of recovery often multiple multiple times. Each had a different but all too familiar path to addiction some a motorcycle recycle accident or dental procedure that resulted in opioids being prescribed and then an eventual spiral into new heroin. Some people have had a lifetime of alcohol abuse that eventually became unbearable. The good news is that all of these people have been helped by entity therapy. Wow that's great. A two thousand eighteen eighteen paper the intertwined roles of Circadian Rhythm and Neuronal Metabolism Fuelling drug reward and addiction. Listen included this diagram showing its mechanism in normalising award arousal systems enabling recovery avary. And I've got that in the article version of this that you'll want to check out to quote Dr Ross Grant of the University University of Sydney Australia win. We fully understand the role of any plus in overcoming oxidative stress which is a leading cause of illness and death in developed countries. It will be obvious why it works to treat beat addiction. A two thousand fourteen clinical study of sixty alcohol and opioid addicts that evaluated evaluated self reported. Cravings I is featured in this article if followed up with the addicts and assessed the severity verity of their cravings after twelve and twenty months and it concluded quote any is an effective detox is treatment for alcohol and opiate addicts as evidenced by a significant reduction in craving ratings. Any D- was effective in reducing and maintaining the number of relapse episodes as well as severity of drug cravings cravings. Any shows potential as a long term therapy in maintaining sobriety through minimizing drug cravings things and preventing relapse verse Ice Chemic- Brain Injury. Animal studies identify a therapeutic era -PEUTIC application treating cerebral ischemia quote. End has shown its therapeutic potential for the treatment of cerebral Ischemia in preclinical studies any deploy US cannibalism were reduced and body. Temperature remained unaffected on effective which proved that N N treatment was solely responsible for this protective effect against ice chemic- brain injury N N N being a successful entity in preclinical. Studies could act as an alternative therapeutic -peutic strategy in this disorder. Let's talk next about any men as a seer to in bio hack. I'll explain gleaned with that means Sir tunes are genetic switches they are chemical switches that turn on and off the genes teams that control metabolism stress response susceptibility to chronic disease immunity our reproductive impulses and much more any D- plays a crucial role in these switches working on repeat that because it's important entity plays a crucial role in these switches working without sufficient energy. Your genes let's get stuck turned on or off quote the NASD findings tie into the ongoing ongoing story about enzymes called CER- tunes which Quarantaine Sinclair and other researchers have implicated as key players in and conferring the longevity and health benefits of calorie restriction. A slew of other health benefits have been attributed two Sirte one activation in hundreds of studies including several small clinical trials. That's from the scientific American article L. A.. Sapient Bio Hacker with true self knowledge knows what genetic black swans are lurking working in their Gino. Antiques preventative measures. You'll want to check out my deep dive article on this topic which is entitled one hundred thirty problematic gene liles. Predicting Alzheimer's Parkinson's diabetes and other diseases. Let's talk about as a model con drill bio hack from the paper on its therapeutic applications in human cells Enemy is available as a source of cellular energy not long ago. This molecule was known for its activity as has an intermediate in anyplace by a synthesis and to quote again from the Scientific American article recent research which suggests it may be possible to reverse myocardial decay with dietary supplements. That increase cellular levels of a bollocks. You'll called entity entity is the linchpin of energy metabolism among other roles and it's diminishing shing levels with age has been implicated in Motto Contra deterioration supplements containing and are a precursor to to any D. That's found intrigues amounts in milk might be able to boost entity levels in two thousand warranties Lube reported that any fuels the activity of cer- tunes including Won The more any D. There is and sells the more One does beneficial things. One of these things is to induce formation of New Mitochondria. Anybody Eighty can also activate another certificate cert- three which is thought to keep macabre running smoothly. Dave Dave asprey describes an AB in his book his motto. Con Drill Manifesto Headstrong which I enjoyed. Which I eh reviewed quote? You're contra need an ad to complete the krebs cycle and produce energy a reduction in in in a d causes all the weaknesses that can stem from a lack of energy in your cells. Now let's let's address and our versus n n n the two common forms of the precursor that you're gonna be finding so one of the first is questions that probably comes to mind when researching MD is which one of these precursors is better. And it's actually hard hard to say at this stage of scientific discovery in many ways we are still in the early days of anti-aging research and in several years more. Human clinical trials will have been done. Research has proven that an in an N. activates the ser- to win cert- three while and our does not I perused a not insignificant a significant number of anecdotal reports from users of both and our and an N.. The common sentiment. It seems to be that N M N feels more like a classic nutro pick. It has a more fiscal acute acute energizing effect. The authors of the Therapeutics Applications paper throw up their hands and admit coat. It's very hard to delineate. The border line between the efficiency of men and an are it is reasonable reasonable to conclude that both of them share some overlapping activities as well as their own positive and negative impacts ax. There's a couple of anti-aging researchers that make the case that an are is absorbed a little better since it. It is a smaller molecule however there are no clinical trials comparing the two and interestingly many bio hackers who have tried both indicated in a survey and in a multiplicity of anecdotal reports that NFL. Then Dan has a more acute noticeable effect. So I guess it comes down to the old practitioner verse. Verse Verse Theorist Paradigm If you're a pragmatic practitioner is the best option. If you have more faith safe in experts theories go with the N. R. If you can afford it tribe both the men and the N. R.. Give each twelve weeks of dosing to see how they affect you differently and I suspect that you may find that. There's really not that much experiential difference difference between the two. Let's talk about sources you want to get pure pharmaceutical grade and M N and which is over ninety seven percent pure not food grade and an food grade is less appear and unsurprisingly. Cheaper whoever you buy it from should supply a COA verifying purity and and explicitly stating that. Its pharmaceutical great. This does not mean that food grade stuff is a total scam and it will still probably do some good but smart consumers demand pharmaceutical grade the source I like is it is infinite age and do linked to them in this article. They also make their products available on Amazon. For those of you who you are going to be having a lot of Amazon gift cards in your stockings this holiday season. Let's talk about pricing. You may be thinking. Wow is this stuff. GonNa you know deplete. My bank balanced by fifty percent. Fortunately for bio hackers who aren't aren't millionaires and an N.. No longer cost one thousand seven hundred dollars per gram. Apparently once upon a time on it did but it's not really cheap in fact when bio hacker reported I've been taking an since July twenty fifteen and the only side effect that I have noticed is a rapid slimming of the wallet. Infinite Age sells a bottle bottle of the stuff for about fifty bucks which to me seems like a pretty reasonable value for a really powerful transformative informative supplement like this. There's another vendor that you're GonNa Stumble across as you research. It called alive by nature and many anti-aging experimenters order from them. In my research I ran across a handful of negative reports about alive by nature so I would urge you to only order from them. If you can verify that they have valid money-back guarantee policy. You might want a to email them you might also be curious about just ordering it wholesale and apparently you have to buy at least a kilo to to get wholesale price on an and that costs about three thousand dollars four ninety eight percent. Pure your stuff so you could either buy a crappy car or you could have a giant scarface style mountain of end n an end that you could just dump on your desk and have a little bit of it every single day and then live forever. Let's talk about experiential experiential. Let's talk about anecdotal information. That is out there. A pioneering and articulate bio hacker who I really appreciate who goes by Lawrence W used N N for about a year and meticulously. He reported the effects and subjective experience that he had on longevity his first few months on the stuff produced some pretty astounding results which I will quote from at length here when I first started using an I. I immediately noticed a slight increase in energy mine wheat beginning to drop within a couple of days within weeks I felt that I was shutting belly fat and noticed if visible flattening of my tummy at three weeks I noticed that the arthritis arthritis in my knuckles had started to clear up within the first month. I noticed that I was sleeping. Much more soundly sleeping about an hour longer in waking up feeling really refreshed and clear minded by three months all the arthritis this had cleared up body wide including my shoulder elbows knees and right hip at the same time also noticed an increase in strength endurance and muscle size about midway through the program by neighbors were stopping and commenting that I was looking healthier younger for more energetic Really good etc.. That's gotTa help with it. The self esteem right one of the more interesting comments was that I was moving like a much younger person after that comment. I focused on my walking dynamics I realized is that I was walking with much straighter posture with shoulders. Back chest out and a looser more fluid would quicker stride as all my joints. Were now more flexible and pain. Free physically I felt like my body did twenty twenty years earlier. I had an interesting conversation with a cause. Medic surgeon friend who said that he could make a seventy year rolled. Look like a fifty year old but he couldn't make them move like a fifty year old. I now believe that N. can can make one move like a much younger person. This may strike as a too good to be true anecdote. It but Lawrence's doctor was impressed by the quantified health improvements. That blood testing revealed. There was a number of those biomarkers that had really significantly improved over time. In fact I'm going to link to Oh those reports in this article so that you can check out that data for yourself if you're the kind of person that just loves up pouring over spreadsheet data. I'll go back to quoting Lawrence. These last three tests were all measurements of inflammation levels in my body. As increased inflammation is tied to aging and a decrease in general health. I was pleased to see my inflammation levels reduced as a chronological sixty year old male. I was pleased to see that my biological age had dropped from seventy years years old to forty four. Wow that's impressive. I found this anecdote especially interesting because after after using it for a while he went off it for a your and then back on it at about half the original dosage postage. He noted that some of the quantifiable health benefits persisted. But some did not quoting Lauren's in summary in some of the benefits appeared to be lasting while others went away after I stopped taking an M. N. overall we're all I felt my initial experience with an was very positive with no downside risk and move on to a couple of the the other subjective effects that are anecdotally credited to an end and you might be saying Jonathan Jonathan Jonathan. These anecdotes are just things that someone wrote on the Internet. Why do you even care and I agree that anecdotes? A singular antidote dote is not the most significant thing because anybody can say anything on the Internet however when I scour are hundreds of pages of what people are saying about something in different forums. What bio hackers? All around the world are saying about something and I see Statistical significance and I also see an alignment between subjective effects that are reported and and the findings that are coming out of the human and animal clinical trials. That makes me really optimistic. That makes my ears kind of pick up. And that's why I'm sharing with you. What people are saying is the result of of using the stuff in a very stringent way a recording the results carefully doing blood testing etc people are reporting increased energy They're reporting this quite quite frequently and sometimes apparently it's an instantaneous. Effective supplementing a fifty nine year old Texan taking between five hundred. Thousand Milligrams Daily reported quote. The big change was increased endurance in the gym. And on my bike I had more and more good days and found I was increasing the weights. I used and getting better times times. When I worked hard? On the bike I still have prostate problems gray hair and sore joints but energy endurance physique and cognition are like I am twenty years younger. An uptick in physical energy is often noticed. I it seems to be a real workout performance. Enhancer Michaela on longevity reported. I recently added five hundred. Milligrams of an suppling willy and have been amazed by the energy boost. I was able to do extra reps with weights and east. Coast Bio Hacker noted that it's a great bio hack four joggers. I do notice noticed that my recovery is excellent Iran over four miles the other day which is good for me getting back into the spring swing and had zero joint pain with barely any soreness. The next day and Australian Bio Hacker commented on its taste and aesthetics first impression tastes great bit like vitamin C crystals but less acidic very easy to take. I dropped half a scoop under my Tong and my mouth immediately filled with saliva. The power dissolved in seconds. Let's talk about its potential cofactors notably reservatrol and Patera. Still Bein are identified in the scientific American article quote. Any deep boosters might work synergistically with supplements Lakers very tall to help reinvigorate motto Contra and Ward Off Diseases of aging while resveratrol has hogged the anti-ageing spotlight over the past decade. UNSUNG researchers researchers in places like Oxford have quietly shown that Tara still buying is a kind of extra potent version. Asian of resveratrol. The patera still by molecule is nearly identical to Rivera trolls except for a couple of differences. Insist that make it more. bioavailable also mentioned Alpha lipoic acid as a potential cofactor anti-aging researcher searcher. Dr Lino explains the synergy between these two supplements quote another benefit of a la which is awful. I poke doc acid is its ability to modulate the state of the energy carrier. Nd there's also another way that L. A. can modulate the NASD H. Two A. D. Plus ratio and even influenced the aging process at at the cellular level through the activation of a class of genes known as Sir Tunes and importantly Ailey supplements must be kept helped cold. So you wouldn't refrigerate Ale if you're gonNA use it and you don't want to just pick up any old alien supplement found in in white plastic bottles on your pharmacy shelves at room temperature. Let's talk about usage and dosage. There's some room for self experimentation with an an end. There's no universal usage protocol bio hackers report taking between two hundred and fifty milligrams and upwards of three grams Daily Lawrence reported. I took thirty four hundred milligrams of twice daily I took my morning dose at seven. Am and by evening dose around six thirty PM after eight months of Over three grams of n daily his blood work revealed that his biological age had reduced from seventy years old to forty four years old. He maintained this biological age. After reducing the daily dosage to one thousand six hundred rid milligrams in Dr David. Sinclair's Joe Rogan interview. which you were what you will want want to watch? I linked to it in this article. He revealed that he takes between five hundred to a thousand milligrams daily and David Sinclair apparently Mixes Mixes powdered an-and with yogurt. which sounds great in Bulgaria? I live we have some of the. Very Bast Organic probiotic yogurt in the world. So I look forward to trying this and you are going to want to check out An article of a bit more in depth article that I did specifically an-and protocol as a usage and dosage protocol. Call where I get a bit more specific about the kind of dosage that you're GONNA WANNA use for different purposes because of course some people are taking an end as a you know it's just something to give themselves a little bit more of an extra edge. Some people using it to hopefully prevent diabetes. Maybe they have some of those diabetes jeans lurking in their genome and some people using it because they have some type of chronic disease that they wanNA address. And there's a little bit different dosage recommendations that you're GONNA WANNA follow so do check out that an usage dosage protocol. I I will link to it in this article. So you're going to have to go find that next move onto. I really cool connection that I a found all on my own. I'M GONNA make the case here. That N M N is a placebo. Hack there's a fascinating book that I just finished. You are the Placebo by Dr Joe Dispenser. You've probably heard of him and this book documents. A bunch of fantastic cases of the placebo effect healing deadly serious health issues is the placebo. Effect is so powerful that it's the one thing that every good clinical trial accounts for as opposed to crediting this to some pseudo spiritual nonscientific non falsifiable phenomena. The book explains that the placebo effect is likely a manifestation of EPI genetic function. If we believe something book hear us that believe Ahah neuro peptides will turn on or off the crucial the genus that we need working to heal us. One of the major causes of aging. Is that our genes get stock. DOC turned on or off and an M N is recognized by the top anti-aging researchers in the world as an EPA genetic hack that empowers our sir two wins to switch on or off our genes. It's kind of a biohacking. Four is smarter genome thus it stands to reason that the placebo effect would be all the more potent if you've been using an M. N.. If you're a rational materialist. I don't blame lame you for being skeptical. The power of belief as almost described in silly metaphysical terms but considering the emerging evidence and the emerging science of epigenetics. I urge you to take any men and and really believe in it. Let's talk about an side effects. Increased appetite is reported. A few you places around the Internet just be sure to stay active and consistent with your exercise while using an m. n.. If you do notice yourself in writing a bit more sleep disruption in the initial few weeks of usage is reported by a couple of youtubers. Apparently they needed less sleep on it. They find themselves waking up in the middle of the night with with the energy to get their day started. which doesn't sound too bad for me? I Give N M N A risk grade of A.. Minus here's why so an is quite safe. It is after all a B vitamin. It's as safe as any vitamin but doesn't deserve an a plus grade because of the lack of human clinical trials trials. Hopefully this'll change in the near future. Though a few other points a two thousand eighteen placebo controlled double blinded clinical trial trial of forty men noted that twelve weeks of end our supplementation at two grams daily. That's kind of a lot was safe. I climbed the longevity anti-aging forms for any reports of negative side effects vex and found none one bio hacker reported. I've taken both N. R. for about two years and then for three months and have had no adverse side effects nor has anyone. I know who takes them the therapeutic reputed applications paper concluded although n an N has shown significant beneficial pharmacological activities in preclinical studies which the scientists have been searching for a long time it still lacks sufficient clinical and toxicological logical data in conclusion and is one of the most promising anti-aging molecules that are are exciting practitioners and researchers alike right now. I rank it among as kick one and C sixty fullerenes colorings as a legiti game changer to watch and experiment with. I am looking forward to taking it myself I self. I've got a package that is somewhere in between Bulgaria and Tacoma Washington. Right right now with it and I look forward to using it and reporting back to you guys about what I experienced and like I said one of the reasons reasons why an immense stands out to me is the anecdotes that people are reporting about. It are are fantastic. It's it's pretty amazing what people people are reporting so I urge you to leave a comment or get in touch with me and let me new. If you've tried it let me know what type of experiences insist that you have had with it and I also love to hear from anyone that has some some insight site or some experience personally with the placebo effect. Because there's a fascinating connection there that I had a real lightbulb. LIGHTBULB turning on above my head moment as I was reading Joe Dispenses Book. I I do personally I would love to see a a study A trial where they did a placebo trial testing the placebo effect. And then they had people on n M N and and they compared people on m N N N to other people and they were using placebo. I it would take some more research for me to understand hand or recommend how such a study would be designed so that it was you know accurately assessing the effect but I bet it would result in something. Something pretty exciting. So that's that's what that's what's getting me Excited right now about the future of the anti-ageing Domain Eh. Again I'm Jonathan with limbless mindset and I look forward to a continued conversation with you and legal notices if you or or someone you know developed or created a concept piece of content or idea shared on this show please email us at Info at limitless mindset dot com so we can mention them in the show notes or provide a back link. We want to give credit where credit is due as a listener to the limitless mindset. Podcast we hope you have and practice common sense however since some of the content covered in this show deals with subjects of a health legal or business nature. This show is for entertainment purposes. If you need recommendations of doctors nutritious or attorneys to console before making decisions that may have health or legal repercussions. Please email us at INFO at limitless mindset dot com.

Quarantaine Sinclair M N Jonathan Jonathan Jonathan Lawrence W Nicotinamide Alzheimer Alzheimer's disease NASD cerebral Ischemia Infinite Age Dr. Lino Dr Joe Dispenser Bulgaria EMINEM Japan Colorado N M N San Diego California Paula
How To Have Boundless Energy with Ben Greenfield

The Doctor's Farmacy with Mark Hyman, M.D.

1:10:19 hr | 9 months ago

How To Have Boundless Energy with Ben Greenfield

"Coming up on this week's episode of the Doctors Pharmacy as we've transitioned into a post industrial era. Where it's very easy to to sit all day long. We still WANNA satisfy that primal urge to go out and move but unfortunately the way we've decided to do. It is to just a soul-crushing workout. At the beginning of the end of the day India have are planning a chair for the for the other eight hours of the day and my approaches the complete opposite. Hey everybody it's Dr Mark. Last year I turned sixty and I feel better than ever. My biggest over a health goal is not just to live a long life but to do it well by saying sharpen active so I'm always looking for ways to continue to feeling great at age. One of the tools that I use is red light therapy from JUIF now a super general non invasive treatment that I do at home we're device with special. Led lights delivers concentrated. Light to my skin. Red Light therapy actually powers up our might cadre which are little energy factories and ourselves and helps them turned food and oxygen into the energy that lets us do the things that we love. And since our might conjure naturally decline as we age and that leads to inflammation supporting the means we stay youthful from the inside out everything we can do to reduce inflammation is a step towards preventing chronic disease and living a longer healthier life and Juve makes it super easy. I can just sit or stand in front of the Juve. Red Light therapy device for to fifteen minutes a day. They have lots assizes to choose from. One of them even fits right on my desk. Red Light therapy is also an amazing way to improve muscle recovering and sleep in Collagen production. So you get multiple benefits at once. I use mine regularly and I noticed my energy is better and better than I sleep better and even my skin looks more youthful and vibrant is such an easy to of. I love using his part of my daily routine so head over to Juve Dot com ports ice pharmacy. That'S J. O. Vivey dot com forth pharmacy with an F F. They are Mac wide to learn more about red light therapy and what it can do for your health. It's a simple way support better aging without ever having to leave the house and I hope you'll check out juve today now. My goal with my diet is use food as medicine but even when we eat super well most of us are missing out on certain essential nutrients. Now our soil's had become depleted and our digestive systems might be considered compromised by stressing toxins. So they just can't absorb as efficiently as they should. That's my always use and I recommend to. My patients use a multivitamin mineral as extra nutritional insurance. It covers the basics for all the day to day functions. Our bodies have to perform that our food might be missing but there are so many products out there. I wouldn't go near because they contain artificial fillers or inactive ingredients. So you have to be picky the one I trust and take myself is athletic. Greens these high quality and highly absorbable forms of vitamins and nutrients from whole foods athletic. Greens comes in a powder that tastes great and mixes easily with water or smoothies and specifically supports gut health immunity energy and recovery. And it's not just the vitamins and minerals it has FIDO NUTRIENT RICH. Superfoods adapted gyms pre and probiotics and digestive enzymes. And I love that. The Ad Justice supporting their powder sin so much of our immune strengthened our overall wellness starts in the gut. It really is the one supplement that covers so many bases that you'd be hard pressed to find something else this comprehensive in one place. I use Athletic Greens in the morning. Part my daily routine and I love having it with me whenever I travel. I also love that. It's diet friendly whether you're Vegan Paleo. Kito dairy free Org Luton Free Right now. Athletic Green is offering my audience there vitamin D Three K. Two liquid formula free with your first purchase. These nutrients are also so vital for strong immune system and strong bones. And many of us aren't getting enough of them. I use let it green powder. And they're D- Three K to formula to make sure I get extra nutrients that complement my diet. So just go to athletic green dot com forward slash hyman to get your free bottle of Vitamin D. Three and Ketu with your first purchase. You'll get it livered straight to your door and I promise you'll feel the difference. Athletic Greens can make in your daily wellness routine and again that's athletic. Greens dot com forward slash. Hyman and. Now let's get back to this week's episode. Welcome the Doctors Pharmacy. I'm Dr Mark Hyman and that's pharmacy than F. A. Place for conversations that matter and if you care about your health and you want to find a way to get peak performance and optimize your body and your brain and defy aging well. This is the conversation for you because we're talking with Ben Greenfield and is about his new book. Boundless which I'm really excited to get into Ben. And you still background on Ben. He's human performance consultant speaker and your bestselling author of thirteen books including things like on training and boundless he played College Tennis Water Polo Volleyball Volleyball Bodybuilder. Thirteen time Ironman triathlete which is impressive. professional obstacle course racer And he's been voted as America's top personal trainer and by greatest is one of the top one hundred most influential people in health and fitness. He hosts a highly popular fitness nutrition. Wellness website and Greenfield fitness dot com. With over a million monthly. Visitors has great articles. Podcast and product reviews. So he's he's the guy he lives in spokane. He loves incredible activities like Ukulele spearfishing bonding planting and forging and cooking. He seeks to help people to achieve performance. Peak performance defy aging and living adventures fulfilling joyful life. Which sounds good. I WANNA sign up for that so important if you saw the pharmacy with F. But you say defy aging defy aging with the with the Ph. I may be so you've been working on this book for three years and we were chatting our tone. It's six hundred pages of its own. Cut Out four hundred fifty pages and it's an incredible testament to how much you know. And what your goals are which is to really provide a road massively. How crappy of a writer. I am was Mark Twain. When he wrote the letter he said I apologize. If I had more time this letter would have been shorter. Sr for a long time to write a short left right exactly so this book is about things that you've always wanted to have out there that you always wished existed in a book but never there. It's a blueprint for upgrading. Your brain for optimize your body for defying aging. So tell us about this book what Star Sort of drove you to write it and what are the key. Take homes Well you know the the the key message of the book for me is really out and energy you know having having boundless amounts of energy at your Beck and call during the day. Most most everything I've written before this has been oriented towards performance towards fatness muscle towards fat loss. Even towards things like you know ironman training and obstacle course training and things that At one time in my life I would profess to be healthy in a in a good way to extend lifespan. But now I know much better than that and iron man's because I am no now well I don't know I I suppose check. We're large enough. I might consider how for back on the bike. But for a million there'd be set there for me to slip back into the SPANDEX and the the Shammy but The the the idea behind boundless was I wanted to focus a lot more on on the things that you know especially in in the in. The fitness room getting neglected everything from hormone management to guts to to the immune system to the brain and I also over the past. Three years have just become increasingly interested in the whole anti-aging longevity filled and so I shall medicine. Yeah pre- pretty heavily into that. I wanted to lay out a lot of different. Dietary approaches and and and in highlight how people can actually determine what kind of diet is right for their biochemical individuality rather than writing just a a diet book or Die Prescription. I worked in a lot of fitness concepts but fitness concepts more focused on longevity longevity of the joints and longevity of the training system rather than performance at all costs you know for example the the strength training session is based on targeting both strength and power we know based on telomere length studies powerlifters. That having this quick explosive wiry strength is good but the problem. Is You know a few use something like cross fit or Olympic powerlifting. Or something like that you know. You're you're in a in a very heavily loaded state or you're in a in a metabolic leagues losted. State can also carry with it. A high risk for injury so for building strength. I like more of the one of the programs outlining. The book is something very similar to what Dr Doug McGovern talks about. His book body by science is very super slow training. Yeah Ten to twenty seconds up ten to twenty seven down single set the failure. You get a really good peripheral. Blood pressure response. You get the lactic. Acid trapped in the muscle tissues and get a little bit of a growth. Hormone release can get very strong with that type of training just one two times a week and of course you don't get those those fast which explosive muscle fibers targeted that want for the longevity component and so in addition to that there's a couple of body weight training sessions that you can do each week. That are more quick explosive powerful but not under load and not in a in a metabolic Lee exhausted. State sounds good. I want that idea. The idea is to have energy in fits and have a body and a brain that respond the way that you want it to but not necessarily for the goals of peak performance or going out and doing an iron man or something like that appear to talk you training for the centenary Olympic during the centenary Olympics. Exactly yeah I got forty years ago. Start Training Yeah. Yeah that's actually a centenary. One thing I think about is can you? Can you get up after being down on the ground? One of my favorite workouts that I do is they'll do a little bit of Cardio. I did this workout yesterday at the gym. So it's fresh on my mind and I do. Have you seen Turkish get ups before with a Kettle Bell? I have my kids do this exercise too and we taught them how to do. It was with a glass of water. And so you'll you'll hold the water up above your head From a position laying down flat on your back on the ground you have to stand all the way up and technically a Turkish getup has some some pretty strict movement regulations. It's IT'S A. It's a Russian kettlebells exercise. You're you're judging it. You GotTa have certain certain movement patterns but anyways you you're essentially standing up with a with a weight or if you're training for balance or nervous system a cup of water over the head and then getting back down on the ground in a laying position without spilling without using your hand without your breaking one hand at hand that's behind you you can use but other than that you're basically up and down off the ground and it's incredibly difficult if someone. It's hard to describe on audio. What if someone Google Turkish get up and look up a video of it Or don't use will use use duct Gore important. Because I remember my dad when I went skiing a few years ago many years died about ninety one but he was in his seventies and he fell in the seascape and he get up and I had to help him up and I think the reason people ended up in nursing homes and not cause disease because they can't tattoos or get out of bed. I think it up so the workout I do I do a little bit of cardio to four minutes of Cardio and then do five of those Turkish. Get up on each side holding holding a heavyweight my head and then all I do after that is i. Sit Down and stand up thirty times and you want to use and they did want interest for the the fewer limbs that you can use when sitting down and standing up from the floor. Yeah there's a direct correlation between that and longevity and just being able to sit down and stand up so do a few rounds of that and I and your hips feel great. Because you're getting down and stand you up. It's very functional when I travel I like very non cognitively demanding workouts where there's two or three exercises and you just do a few rounds and that's a that's a good one. Yeah that sounds before. We started the podcast. You're down on the floor. Show me the five Tibetans warning So I was like all right. I'm gonNA write those doubt. Are they in the book? Yeah there's there's a whole chapter on on beauty and symmetry how to optimize your workplace ergonomics in terms of you. Know the type of pelvic shapes tools that you can use instead of chairs There's there's a very soft map that I like. It was. It was created by the Swiss inventor in patterned after the Korean rice paddy fields. He's walked walk in those and finally his feet grew very strong and his low back. Pain went away and so he developed these mats. That you can use a Standing Matt's station so I've got all these different things you can sprinkle around your office to optimize your your bio mechanics during a workday which which definitely plays into symmetry. So it's like having a trainer in a book like Greenfield's in the buckling do yeah. Yeah and you know. And the symmetry chapter also has a whole range of exercises in this originally just exercise. I give my clients to do on on airplanes and to do and they're waiting for an airplane takeoff when they're taking their little movement snacks during a workday stopping every thirty five to fifty five minutes to do few stretches. So you know. The sample exercises are You know different moves called foundation. Training moves decompressed the Spine. Use Your own body to decompress your spine. L. Doa stretching which is a form of of self. Mayo facial stretching where. You're actually kind of pushing through very extreme range of motion for a minute and holding just to mobilize the FASHA. A lot of different foam. Roller moves basically all the things that you can do to kind of get the body moves like like you have to like start here and do these things or this is the program must choose your own adventure but but what it is it's like. Here's here's six different three to five minute routines whether it's although routine or foundation training routine or certain series of stretches or these longevity exercises stop at certain points during the day choose your own adventure pick which routine you want to do all it takes three to five minutes do that and then just get back to work so either by size forms of working out that have a huge impact that you can do anywhere that you don't go to the gym for an hour. Two hours right. Get All sweaty messy. Yeah I mean the gym really our our gym culture not to get too much up on a soapbox. But it's you know the these hard core soul-crushing workouts at the gym. You normally one hundred years ago would have been relegated to the realm of the warrior soldier. The gladiator the the person who wouldn't necessarily be expected to live a very long time but had to be in good enough shape to very hard to kill you. Know and as we've transitioned into a post industrial era where it's easy to to sit all day long. We still want satisfy that primal urge to go out and move but unfortunately the way we've decided to do it is to do just a soul-crushing workout at the beginning of the end of the day. And then you have our butts planning a chair for for the other eight hours of the day and my approaches the complete opposite. I think that if you move all day if you're using a standing or treadmill workstation taking your calls while you're walking outdoors in the sunshine taking these movement snack breaks keeping maybe kettle bell movements sack race. We got pause on that. That is the greatest movements nest now all day long. Not The way nothing like six to ten small meals a day. Yogurt and carrots sticks bar. There's no evidence eating more than two times a day. Do anything pretty much. But the movement snacks that's a movement actual movement snacks. That's the thing with the With the exercises. If if you've done then maybe you keep a kettle bar or a kettle bell or or like a hex bar right. I love a Hex bar allows someone even with the compromise back bill. Lift a heavyweight up off the ground. Yeah or pull up bar for shoulder decompression on AO hanging in the door the office and you just create an environment where you can move during the day as much as possible and I think that if you structure things correctly that formal exercise session beginning the the end of the day should be. The icing on the cake should be an option in training for for Triathlon Nora Spartan Race Orion or something like that like yeah you do need to go to the gym and do something that would be considered somewhat unnatural because even unnatural ended mine. Right YOU WANNA go to battle On a case like that you've got to beat up the body but I think we should structure our days and only for symmetry but these movements throughout the day and then Yeah in the in the in the in that whole symmetry beauty section. I also get into other things like I. I do I'm very into into the face right now. You know like getting rid of wrinkles taken care of the skin things like that so I've got this thing every week now. I talk about in the book but I do like a clay mask over. The face was dermot rollers. Yeah all along the face the clay mask and then you use an infrared light. Like one of these new photo modulation panels like a Jew. There are others but the Yeah the Jews like one of these old Juve. Men's you can keep your in your bathroom. You should have that on your face about ten minutes listening to an audio book listener. Podcast whatever and then you rinse the claim. Ask honest so it tells more about the days when like here because people aren't really familiar with and you write about the handbook. Is it credible therapy for optimizing our body and our brain? Yeah well I mean light in general's fascinating. I don't know how much you've you've you've looked into light. I'm reading this book right now. Called the human photosynthesis actually gets into how the Human Melanin pigment actually operates very similar to the chlorophyll pigment in plants terms of being able to accept photons of light and generates a think for for each molecule of water. It's about four electrons which can then be used to move through the electron transport chain and technically generate. Atp based energy how? Our body makes energy so human photosynthesis the electron transportation. We make energy. But normally you'd feed glucose cycle to make energy you can use the combination of light and Melanin to produce energy and I had already known a little bit about that idea of some element of human photosynthesis. I think it was sired. G who published an article on on Greenman maybe five years ago and it really come out. He was talking about how upon ingestion of chlorophyll rich compounds you saw similar effect chlorophyll rich compounds combined with sunlight like fido plankton or green blue algae or coral or spiraling or something like that but it turns out that just. Melanin alone you know. Even in the absence of a Lotta these green blue compounds combined with sunlight can shift you into a state of producing electrons so basically might kind really charging the body's battery yeah and so people don't really understand my contract. The little energy factories in your cells need take oxygen and they take food and they burn them. That's how you have energy to run everything. But what you're saying is that light also can contribute to the rejuvenation of your Mitochondria which is central to aging or any of that in the discussion of Melanin. Aside we know that certain spectrums of light can activate an element of the medical side of clumsy oxidise. And so anything about the six hundred to eight hundred fifty nanometers spectrum of light and this would be like Red Lights Infrared light some parts of foreign for like fall into that spectrum. But it's normally near Red and red. GonNa target side of Chrome Seok. Today's it's actually wonderful for the motto. Qendra you get nitric oxide. Production you can trigger Collagen lassen production No really good. Human Clinical Studies that I've seen but a lot of anecdotal evidence. Anything Juve is put out some articles on their site about up regulation of Mitochondria activity and leg cells in the testes. So there's there's an amplified Total Dawson. Response of men are using way red light on you and your testosterone goes up. Yes your clothes in front of these red light panels and so you get the skin effect and you also get the endocrine effects. Wow that's pretty amazing effect. Yeah so I mean. Nothing's shine it on your your shining on it. Park guys and there are multiple ways to do it. I actually traveled many ones. I'll lay in bed at night. I read a book and you know kind of Tuck it in my crotch and for about ten minutes wow home I have one of the one of the big panels ends up. My desks can stand it that while I'm working on my desk you don't want too much some. Xm Today Yeah. Excess stimulation of some of those nitric oxide. Synthase pathways and that excess stimulation of side of chrome oxidation the motto Contra can generate excess free radicals right so this is something you could overdue in so many could overdue. Uva NEWBIE be from sunlight. So it's a little too much charge and that creates secondary damn right so you're saying access In this case it would be reactive. Oxygen species so like response excess metabolic activity. So you know we we know any of these things that might induce a mile medic effect from cryotherapy to to exercise to heat they would be unfavorable in large amounts. But okay wait wait so what you just said something. That was very cool concept which is hormesis hermetic. People have no idea what that is. Most people never heard of the word and what it means. Is that when there's a stress to the system? It activates a healing response a little bit of stress. If you exercise and lifted it's going to create a little bit of micro damaging the muscles but that makes them stronger. Yes so assuming you allow them to rest and recover and and the same could be said of radiation. There's a there's one study that showed that the rodents around Chernobyl we're living longer than non irradiated and irradiated rodents so this others some evidence. Even mild amounts of radiation may be beneficial. This might be partially. Why Irving and grounding in going outside barefoot getting exposed to that type of radiations beneficial lower risk of skin cancer with frequent sane exposure to sunlight due to that effect on building up his callous shock. There hey with the cold that that can accessibly activate the sympathetic nervous system. It can stress the immune system. It can be too much but in small amounts right you get nitric oxide production and you get that activation the vagus nerve and you get a little bit of conversion of your adipose tissue metabolic reactive brown fat and so small amounts of cold good large amounts is. Anyone knows who's maybe not dressed right for a day of skiing it can be. It can be stressful You know heat same thing we know from like the Finnish longevity study the longevity study that Sauna and the Sauna and and you see a distinct increase I do. I do a hot steam really hot and then I jump in an ice bat. That's that's what they left out in that study. I think is you know because I've gone to Finland and and I've I've gone jumping. They jump in the ice. They'll they'll go on the sauna and it'll go jump in the Baltic Sea standing outside to dry off shivering and then go back and do a few rounds of course there's the social component right there with their with their buddies hanging out the when he'd go on the Sauna your quiet you breathing and on your phone. So there's there's some components that go beyond the sauna and I remember once I was. I was in Maine. A friend of mine had a woodfired sauna and we literally sat in there for six hours. Yeah I'M GONNA go back out in the snow and roll around in the snow mazing. I didn't get back in this honor. Roll around snow it was. I never felt that good in my entire life. We do that at our house. My Kiss Calm Snow. Angels and and what we'll do is do the sauna. Then as you're walking out trudging through the snow to the hot tub you stop you do stone as you get in the hot tub. Get Fat Tingling in the scandal back out and do snow angels and the idea of hot cold you know again for the effect is fabulous. I talk about this in the book. A little bit and it's kind of it's kind of a lot of people are talking about right now in the whole the whole nutrition scene. Is this idea before summarize we got movement snacks movements okay? Great concept and idea and there's lots of those in the book we've got activating your energy system with light right. Kinda like Juve and we have which is giving your body different kinds of stresses to activate a healing response is hot and holds etc. It doesn't kill you very simple. Powerful ideas even corporate into routine. And I I've been doing all these things because there are actually so essential to life. I have a juve. I do movement snacks a lot. And I do hermetic stresses with hot and cold and I think it's. It's really how I stay. I got my telling you done recently. And I'm sixty but my teller thirty nine so I think we can reverse the biological clock by being smart about these little micro hacks than anybody can do to optimize health and your book is just follow these micro. It's free a lot like if you think about cold. Yeah you could go pay seventy bucks for a crowd therapy chamber. You could go go go for a walk in the coal and you you could buy one of the whatever eight hundred light panels or you can use sunlight similarly. You know swimming. You don't have to me neighbors. Who are watching tenure tenure? Junk out in your the The thing is though about the spokane. Our problem hasn't been the forest sunlight. Threes Zeno Hormuz though is also very interesting. This idea that that plants have built in natural defense mechanisms that also in a hormetic response and you know this has sparked movements like the Paleo Movement and the Carnivore Movement and you know Paleo Movement kind of restricting you know many grains and soy in some of these some of these compounds have built in defense mechanisms. The Carnivore Diet takes that even further. You get rid of Kale Broccoli and cauliflower and most herbs and spices because of that mild amount of damage that these plants can cause the body. But I mean when you look at a lot of these blue zones longevity hot so vast array of herbs and spices and Zeno Hermetic compounds. Yeah they're not doing You know like the the they're not eating boatloads of keen wall that hasn't been rinsed and so right and sprouted to get rid of the the soap like irritants opponents that cover the keene. Wa and you're in many cases the the gluten is being slow fermented like soured o'brady free digest the blue on the Dick Acids or you know or soy for example. Eta Mama is is not quite as good as me so or ten day or Natto. Because it's been ferment. In so I think it's proper preparation and deactivation of some of the Natural Bilton plant. Defense mechanisms allows you to enjoy those foods were shoving side the argument whether or not those foods are necessary. Which is Karma Diet? Folks will say. Well he'd get eating properly apprise nose to tail diet you get all the vitamins and minerals and everything that you need is far more nutrient dense any plant food. Ever livers is nature's Multivitamin but at the same time plants are fun. It's fun to gather round prepared meal. And whatever may mom's casserole and grandma salad and some beets and going Jeez Rubella and Rosemary's like you know there's a lot of cool stuff on the planet that we can eat. That goes beyond just animals. I I just have to be smart enough to deactivate these built in defense mechanisms. But even those because you never going to be able to fully deactivated. They're not necessarily the principle of Zeno Hormuz plant based defense. Compounds can actually be good for you. Insane amounts yeah. Let's this is an important sort of come back on this because you know I had this theory that I kind of made up as hard to learn about plants and the phytochemicals and plants and the way in which they interact with. Their biology called symbiotic fido adaptation. We've essentially means. We Co evolved with plants using their quote natural defense mechanisms that they've developed in response to stress or protect themselves and those molecules activate healing responses in our body or activate different pathway. For example you know when you have a wild plant. It's under a lot of stress. Yeah right organic more than conventional rather than the big fluffy right. Well Sure Organic. Or what's wild it actually far more nutrient dense For example Dandelion Greens. And you can pick up off your lawn. Have you know thousand times more antioxidants benefit than for example spinach? Which is a superfood right Same thing with little small potatoes are far more nutrient dense those big yukon gold potatoes because they had to work hard to address tech themselves dress. So we use those molecules Mike. The Night Glucose analysts for example. The Broccoli family that help us detoxifying protect ourselves all the antioxidant colorful compounds are all these phytochemicals and there are more of them. In stressed plants. Like wild and I think you know in your book you talk a lot about aging and this idea of how do we activate these different mechanisms in our body that promote healthy aging and they reverse biological aging and I WANNA get into that? Because you know there's a whole chapter antiquing in book you talk about everything from pep sides to stem cells and any which I definitely want to get into which is Lincoln and my derived aside and that is a very powerful anti-aging compound that is getting a lot of news and press and people using But one of the things you talked about and made me think about this because of the you know the explanation disease. Hermes are this category of combat. It's called stacks sti or tuned active compounds now sir tunes for People. Listening are a superman mechanism for regulating and some resistance and your Mitochondria function and longevity and those are things when you see these calorie restriction. Studies are intermittent fasting or fast mimicking diet ketone diets. Those are all activating. These are tuned mechanisms which master genes that regulate the aging process and health. And the only the only come with certain kinds of stress in their plant compounds activate these so. Maybe you can help help us understand a little bit more plant compounds can activate your to activating compounds and win when those are combined with any or eighty precursors it's actually very productive for the DNA because both of those can work together to repair broken proteins to keep DNA strands from being damaged. It's a process called a seat elation that these tunes act on along with an ad to protect your DNA. And I'll I'll explain how to get some more of those but I I would be remiss not to mention. We're talking about the wild plants. I'm fully agreeing with you. I read a book a long time ago by Joe Robinson. Called eating on the wild side just one of your family and I plant forage and do a wild plant pesto. And it's very very simple and anybody who has wild plants growing nearby even Dandy. Lingering can make this so some of the main things. I've grown my property. Nedal which caused a whitetail deer around there. Just get fat nells full of amino acids and fatty acids the steam nettle so our harvesting. I also have wild mint out there so you can feel the staff square. Roll up leaving your finger and sniff. It smells a little not so get a little mint in the Dandy Lion Greens. Those are perfect so a bunch of Dandelion Greens. And sometimes I'll swing into our garden grab some Rosemary. Some time you know. Spices often throw e regardless stevia leaves and Kinda sweet. I'll throw those in there. So I come in. With my with my big bagful wild plants and all you put that in a food processor and you put about a cup of a really good extra virgin olive oil in there and he put about a cup of your favorite your favorite walnuts for this and he gets them salt. Those the those that are you can do garlic I I personally low fahd map diet so I I leave the garlic out and Parmesan cheese is also something that can give it a little bit of a mommy flavor. But if you WANNA go dairy free I I'll actually ferment. The Greens you can just leave them in a jar and ferment. Then a little bit away from Your Yogurt and they developed this fermented Hamami flavor. If you WANNA take a little more time to make your pesto. Yeah usually you dump all this stuff in the jaw you press go and you you blend it for about a minute in this wild plant pesto. When you add the olive oil on the wall for dinner good and I'll smear that God of a steak and I'm I don't anything else while plant pesto stake. I'm good so back to the this tunes though so you know. Most people are familiar actually with a lot of these two activating compounds. Red Wine and blueberries Kale and a lot of the dark purples and Greens and reds studies on the red wine thing on rats high levels of her spiritual and they were able to even though the rats were eating badly. Nitrous is to transform their metabolism increase longevity. Not to change you. Eat Bad not exercis- but it was powerful. The only problem was what they did was. They gave them fifty the equivalent of fifteen hundred bottles. That's why you're not GonNa get just from drinking. Buying supplement forms made from peanuts skins not grape skin so there's kind of a kind of allergenic component to choose your reservatrol wise. I'm I'm a big fan of Tarot. Still being for those reasons molecular lead acts very similar as very trial is a stack activator. But it's a lot more powerful you need less of it. Yeah so often in a lot of buying supplement that with any yeah exactly and that. That's what a lot of companies are doing are combining in a d with some of these two and activators and then typically some kind of a methyl donor B. Vitamins Beach Ball. Beat be tain trimethyl lysine methionine and any of these things that are going to contribute methyl groups. Anybody who we we can get the second. If you WANNA can explain that a little bit more whether you I do want to get into with the With their Sir tunes. Talk a lot about these stacks in the book and how magical. They are especially when combined with intermittent fasting or restricted feeding windows or or some amount of calorie restriction as far as protecting the DNA assuming that you have enough in a d because her to work with the NASD and Eddie levels will dramatically decline as you age so you need to have two levels elevated but then also have your ad levels elevated in one of the One of the cer- tune activating compounds. That there's been an a little bit more research on lately. That's very good. Ser- TO IN IS FA- Seton or Fi Seton. Yeah and there's Persimmon and onions strawberries. Especially wild strawberries new you can. You can buy strawberry powder and added to your smoothie you can. Strawberries are easy to grow the weeds. But there are very very good source of this Seton which is one of the more potent stack wild out there. Yeah and you can buy the wild wild concentrate strawberries. Yeah you can buy. You can find organic wild Strawberry Lady Get Yeah. Turner smoothie into a fruit loop so anyways. The tunes are good but because they need to work with any D. Which is also going to be very protective for your motto Qendra during Metabolic Activity. If you're eating a cer- to enrich diet but neglecting to keep your energy levels elevated you really shorting yourself from a DNA protection standpoint which is all the more important now that we know that. Some of these forms of non ionizing radiation like five g and Wi fi and and non native. Emf May actually impact DNA. And so so if you can do things like get your energy levels elevated activates for two wins You know when you get exposed to a lot of this non native math. Typically there's a huge influx of calcium into the cell so you keep your magnesium levels elevated to battle that activate some of these other anti-inflammatory pathways. There's one in particular called the nerve to pathway that you can activate with with key tones or with being in a state of Kito Service. You know there are a lot of things you can do to protect yourself but I would say top of the Totem Pole for the DNA would be sir tunes and NASD. Okay let's back up a little bit because people probably don't know what any idea so. Yeah so you know. In the body there is inside every cell. Hundreds of thousands of these little factories called conjure your power plants and as I said they take oxygen. You breathe and food that you eat and they combust them. And there's a whole series of chemical steps and and basically a cycle has to work if there's going to be functioning and it's regulated a lot by various genes like the ser- to in jeans and Daf two Fox these are these are genes that actually regulate the aging process so on scientists and I was recently at a at an event where I was listening to the head of the Buck Institute for Aging Talk about an ad and talk about the might of Khanjian some these genes they literally in in by by actually helping properly regulate for example one of the genes deaf to in earthworms they were able to spend the lifespan. Evatt worm that would be equivalent to us. Living Two thousand years old and things that turn off our sugar and processed food and toxins and ems. And why fight all the things you mentioned. So do you know how old you are more years now? I don't know about that was two thousand but what you're talking about is how the science of aging advanced so far that we now understand the mechanisms and we understand how to play with them in ways through the movement snacks. Some of the other things alight there but also through the right nutrients and supplements and any D is one of the key parts of that cycle of making energy and and many of us like you said decline as we age there are ways to increase it through various modalities including certain supplements like hot topic. Now baby any people are using from a traditional standpoint. You can fast. You can eat a wide variety of fermented foods there are certain. Tea's like a POW Diario Bark Tea. Which has these. These compounds called Beta Kappa chains in it. Which are wonderful for increasing energy levels and so so there are and of course you can. You can make sure that you're not turning over in eighty two quickly by paying attention to the level of exposure to non native. Emf Turn your phone on airplane mode when you department of New York City and I look at my wife. I news four hundred different networks. I you know I wanted to build a Faraday cage around our apartment. We're actually we're actually looking at buying a net and literally it goes over your bed. That shields you from all em. I'd use paint if you if you can for your room. Faraday paint yeah others. Faraday paint shielded healing has has faraday paint. If you don't WanNa ruin the function of the room can appear on the bed. Okay that's a good thing to know everybody. Fared a paint verde is a scientist a physicist. Who Kim this Faraday Cage? We'd send it blocks out all radiation and and I think that's a powerful idea that we should think about because it doesn't fix sleep at thirty cage underwear when I'm on the airplane and that it's not here yet but he just got a Faraday Cage Hoodie that like I pay attention to this stuff but yeah part of it is because of the NASD and And by the way might a contra the most important thing you need to keep healthy through aging and they degrade genetics Dna get there easily are super sensitive and we don't know how to take care of them. Pay attention to it. It's not something even doctors think about or talk about. Let's just for the good news is it is the center of the agent conversation and it also something we know how to deal with in what we can do about it. So that's what's exciting. I spent a lot of time. In functional medicine. Treating People's medical issues with all kinds of modalities including things. You're talking about. Yeah so So the the the nicotinamide nicotinamide added nine nuclear todd that that's basically NASD. It's unfortunately not very well absorbed if if you just take an oral. Na D Supplement. And so what you'll find out on the market now are two different forms of of eighty precursors one called. Nra nicotinamide right beside the overhaul which is Nicotinamide Mono nucleotides something something anyways though. Npr is actually pretty well absorbed orally and so a lot of supplement manufacturers chrome accents and thorn all these people and are now as one oral way to boost energy levels And then you can't necessarily swallow as a capsule but it can be you can buy. Subway will enin tablets. They actually sell him in capsules. Yeah well they shouldn't because it's not very well absorbed unless it's dissolved suppling really. Yeah and the thing about an is. More of the nicotinamide will be in the hypothalamus. And in neural tissue in response to amend supplementation versus and are supplementation. So you're doing for the brain effect I would say use sub lingual or use. They make these now international. Nfc sprays if you just want a quick full-body fact our works just fine but you make sure kind of backed what we hinted at earlier that because he is going to up regulate your methylation pathways you take a methyl donor along with it. You know like beaten trimethyl lysine or Sammy or something that will make you feel a lot better when you take the NASD now. I suppose there's someone's you can buy over the kings eighty sprays. I think prescription right. No you can buy that alive by nature. I know has one right now. That's one company De sub sub. What do you trust the volley in the brand will there? I know the people who run that company and they're they're pretty committed equality and manufacturing gym facilities and it's I think they do a good job. However the NASD levels are still something that I think you should spark a pretty significant increase in prior to supplementation by doing something like an IV and in terms of increasing bioavailable ad. Nothing beats that meaning that you actually sit and get a five hundred thousand big ad drip into your system and many people do this for one to five consecutive days to top off the ad levels and then use oral supplementation after that draw people experience in once a month or once every couple months to Redo an IV to get the levels backup. And that's what I do I get. Iv about once a month I take and amend right now subway in between those doses or between those IV's and the other thing that I do because the one time I know I'm exposed to tons of radiation inflammation non navy method CETERA. Is You can get these transdermal patches now that using electrophoresis patch to actually deliver any DeTrani thermally and so I'll wear moves and hatches. That'll slow bleed about seven hundred fifty milligrams of any D- into my system on flying. Yeah that that's a that's a very useful way to get transdermal deliver. What do you notice any difference? In how you feel your performance and energy the energy would would the biggest one the enemy if I take that prior to workout I get almost like a mild flushing reaction like a little bit better blood flow. So there's that The DNA protective effect. Though is something that I think is best measured with what you're using to monitor your longevity telomere length analysis or one of these new methylation clock analysis because some of these things. You don't know they're working until you can actually see the fact that they're having on telomeres on DNA. Pretend so I mean. My last specter sell telomere analysis. It was nine years old as far as biological age and one big change that I made was doing for the past two years using that method that I just described nine years old nine old. And how old are you in the thirty eight okay? That's impressive so so I you know who knows when you're stacking all these modalities what's actually working but ultimately the NASD. I think is even if you're not doing IV's or patches or whatever and you're just taking oral NASD if you're doing that and including ser- to enrich compounds in your diet and some methyl donors. That's a pretty good staff for longevity. Wow that's a lot information. So in order to upgrade your Mitochondria and help you live longer. Have More Energy and repair your DNA. You're talking about using any in different forms and men Sub Lingual Patches. Iv's which is available now more and more clinics around the country including all in the center in Lenox Massachusetts where where practice and you're talking about adding compounds that are like the red wine but That you can actually get from strawberries. Wild strawberries and other plant foods And then you're talking about adding things that help with cycle methylation which is a really critical cycling your biology and your biochemistry that is going on thousands millions of times a second and it needs helpers and things like. Sammy methyl lysine and drinking wine. Same same as you were talking about with with With stress and wildness drink a wine that has been from a grape. That's been grown under stressful conditions. Like a lot of big California cabs in. Lowe's they heavily irrigate their crops developing very sugary. Assad low antioxidants. That hasn't been stressed as much. So yeah you know. We've now gotten the health sector companies like dry farm wines for example that are that are doing more of like a like a lower. Gatien grape crop if you look at countries like New Zealand or Italy or France when he had a steak house usually those those type of countries that are still using old world. Biodynamic methods with lower. Dacians can't even consider the wildness of your wine. Okay I wanNA talk about Diet and sleep so in your book you talk about how. Obviously there's no one died for everybody and that you need to figure out what the right diet is for your body But there are some common themes so tell us what those are and how people figure out how to eat themselves. Yes it's interesting. I mean all all the way back to Roger Williams book biochemical individuality I mean there's a vast array of different sizes of livers and stomachs and there's different rates of excretion of uric acid and vitamin D. And you all sorts of different ways that we respond to different vitamins and nutrients and a lot of that is based on genetics. And so we cannot say that. Let's see Ketogenic Diet. That might have helped your neighbor lose. Twenty pounds is going to be appropriate for you because maybe you have familial hypercholesterolemia there may be. Have a an F. T. o? Gene that predisposes you to gaining weight in response to high levels of saturated fat. Maybe you've got poor. You know liver bile production or gallbladder bile release. There's there's something going on at least a high fat diet very right for you. You know and and the same could be said for. You know whether you're maybe you're under meth later and trying to get by on a on a largely plant based Diet when in fact you need a lot more methionine methyl groups that you got including meat in the Diet and so there's a great deal of individuality with diets you know. It's I've never really written a diet book. Just because it's so hard actually dial in a specific diet even even in boundless. I actually outline thirteen different diets from the walls protocol to the plant paradox protocol to the Paleo Protocol to carnivore approach all these different approaches and then walk people through how they would find based on genetics blood testing stool testing urine testing food allergy testing. Which die is going to be appropriate for them? And even then it might be a transitory diet or like maybe you have leaky gut an auto immune issues and there and high levels of mercury or or something. That's going to require more of like an autoimmune or detoxification approach for eight to twelve weeks before you progress into a more kind of free diet or a diet that might be less restrictive so ultimately a great deal of individual visualizations necessary with. I think probably the most important first step being to look at what your ancestors ate. And try to. In some way simulate that if you can I mean if that's the lowest hanging fruit is a very simple twenty-one about my ancestors meaning the ones like in the last one hundred years or two hundred years because you are two hundred shops that my ancestors? Mcdonald's nine hundred says and you know God that's dubbed was. Only you know you can look at things from an ancestral standpoints okay. I'm largely northern European. I'm probably GonNa do okay with things. Like firm ended food. Salted Foods fish meat etc. Or maybe I you know I come for more like a South East Asian or sub Saharan African ancestry. So I could do better with a little bit more. The citrus fruits maybe some of the higher carbohydrates coconuts potatoes. Things like this so you can. You can get some decent idea of your basic ancestral food choices just from knowing your where where your ancestors came. Yeah but I think it's smart to delve more deeply into that. Get a good blood test. Urinary Hormone Hamas. Most of us are these days got like ninety nine percent Jewish from the east. I I'm like I'm like one thing right and mostly Blair which might actually be more free with our diets who who knows. It's difficult to say but ultimately you do not want to assume that whatever the prevailing diet is the most popular book in the bookstores. Going to work for you at this point in your life I always say the smartest doctrine room is your own body customize. Yeah that being said as you alluded to there are prevailing characteristics of just about any successful diet including those we see in longevity hotspots McCoy oh or Sardenia or Kanawha and a few of those components would include some element of caloric restriction or fasting. Even look at the Mediterranean Diet. Right which we've bastardised in the US to be as much goat cheese and olive oil and fish and even you know red meat and spoonfuls in spoonfuls of nut butter and eight handfuls almonds during the eye when in fact traditional Mediterranean Diet if you look at the Orthodox Church and the the amount of fasting and religious observations on that. Diet there's huge amounts of protein restriction. Certain days of the week were all of oil isn't even consumed. You almost like a press pulse cycling of times of the year when you're eating adequate calories and especially adequate protein times of the year when there's protein restriction meet restriction calorie restriction so. Almost every single diet has some element of calorie restriction. Whether it's intermittent fasting are some religious observation of fasting. Some element of protein restriction. Not Year round right. But there's always something reset actually sets your biology right and for me fast while to sixteen hours every day overnight. Twelve sixteen hour fast once a quarter. I do a five day calorie restriction. Similar to Vaulter longos fasting mimicking. We're just for five days. I eat about forty percent of the number of calories out normally consume and then one to two times a month. I do a twenty four hour dinnertime to dinner. Tom Fast and for me. That's sustainable all year long. It's easy to remember. There's there's nothing super ten-day water fast. All just I can sustain that throughout the year so fasting is one component. Another component is eating in a Paralympic state usually with people. I mean when you relaxed when you relax yes in your car on the way to where in your car you know. Last night I give dinner. Talk everybody's talking and chatting they bring up the food and the ready Divan. I'm like wait a minute. We have all these people just walked in. They've been at work all day. They're stressed out half and we're checking their emails on their phone and they still walked in here. You don't just sit down and eat in that state you know and at our house at the Greenfield House. We all take at least three depress in through the nose out through the mouth again and again and they will say a blessing over the food and then once the meal begins. It's all fun games. We play table topics. And we have all these different card game. You know exploding kittens and unstable UNICORNS and bears versus babies. And all these games. We feel funny. All cards are a little grease stains autumn and stuff. Because we're always playing cards over eating but this idea of eating and not just a relaxed rest and digest Paris pathetic state but also eating with people in the presence of others not hunched over your computer having salad or huffing down eight hundred calories smoothie before you know it is gone because you've been looking at your emails a little time. That's another component We also see as we also talked about. Typically a large inclusion of a wide variety of wild plants A lot of the Zeno Hormetic. Cardi get for great. Yeah Yeah I mean. Farmers Market Community supported agriculture patio. Food I say. Eat Ugly Weird Foods. Yes assuming a weird food is not a coconut in crested. Deep Fried twinkie. Yeah and if If I could if I could throw probably a couple more in there it would be typically not having a very large meal close to bedtime. There's another two three hour. Lindley asked about sleep is one of the best ways to keep your body's core temperature low while you sleep and if you do have a late dinner like I had a late dinner like eleven last night I'll get cold. We'll go for a walk. I'll do something they'll get that core temperature back down so last night took off my I went for a brisk walk. I Walk for fifteen minutes before I got my back home or hopped on the taxi. Back home just so I could get my body's core temperature down. Yeah cold shower cold soap or anything like that. If you have to eat a late meal is a good idea. So ultimately th- There's about twelve different factors that go into the book that are prevailing characteristics of all of these areas where despite no matter what the Diet is whether it's a plant based Diet and Loma Linda or you know fish and rice and Okinawa. There are certain principles that you follow such as fasting eating with not having huge dinners right before bedtime that no matter what. Diet you're eating allow to be more successful mazing. So in terms of the whole begin. Meet thing we talked about these blue zones but the truth is they did eat meat pork and know in Costa Rica the Guinea Pigs. Oh Yeah I bet. They're not the trick with meat really in my opinion. Is that when you look at 'em tour activation to difference compounds are GONNA go? Kay listening is essentially one of the regulatory factors around Anabolic switch that if excessively activated can accelerate aging but if activated within reason can do things like maintain muscle maintain bone density allow for repair for covering four months etc. But if it's constantly activated that's a condensate of pro growth that can accelerate aging. Well the the two things that you want to be careful with if you are including a lot of meat or proteins in your diet is extremely high amounts of loose scene and very high amounts of methionine and so with methionine. You would get that if you're eating carnivorous diet. But the lion share of the animal based foods that you're consuming were derived from muscle meat rather than from things like bone broth bone marrow organ meats liver kidney hearts the these foods that are richer in not only some of the nutrients are turning back. Deliver being nature's Multivitamin also in lysine an amino acid which helps to balance out those very high amounts of methionine Argon. Include in your diet. I think it's important to eat nose to tail. And most people don't like organ meats properly awful for reason but it I mean and and if you don't like to do that there are companies like like Paleo Valley and central supplements that are selling now like Like liver powder deliver shake prostate brain. Hard like you can just take capsules. All use these a lot of times travel allow organ meats when I'm traveling so ultimately that's one issue the other issues high amounts of loosing And this is something I think is a bigger problem in the fitness world because any supplement manufacturer knows that a good way to make money fast as to sell branched chain amino acid supplements which unfortunately in the literature have not been shown to be that great at all for performance or recovery is just basically glorified flavored water. But it's isolating valvoline and losing in branched chain amino acids and so if you're relying upon a lot of these popular protein powders that are adding extra as to the protein powder using vca as when you go to the gym There is now a bunch of different companies. That are putting. Bca's in there like a bang energy drinks and some of these others. They're adding to the energy drinks artificial sweeteners and everything. Being a ton of losing and losing is another potent activator but it also helps. Muscle synthesis. You can't build muscle. They should have adequate loosening which is not so much foods you can. But you don't want it inaccessible. Think a lot of people are getting too much meaning and too much loosing when they shouldn't be getting more glazing and so I think if you are going to eat a meat based Diet and you know I I love me. I bow hunts. Prepare meet all the time if my my wife does a lot of the cooking at our house but if there's a steak or chicken or fish and he's be cooked. I'm on the man or an origami in so I eat meat but knows detail and cogs versus glossing versus losing consumption. So how do you? How do you fix that Saudi? When he when he was saying. You know you you sacrifice some of the muscle meat consumption and instead include things like bone broth liver kidney heart or capsules You can sell them with. Lysine can use Some leising it offset the fact. Is that what you're saying you can offset some of the effects of Mathiason. It's your methionine lysine ratios. This is in your camp when I sit down to lunch. I have lunch. Typically for me lunch will be like some like a little bit of These days I'm alike. Pumpkin squash some of these underground storage organs. Typically a bit of ferment on the side like Kimchi or Sauerkraut and that some sardines anchovies. Sounds like my diet herring salmon but I now have after after seeing a lot of stuff bug license of a big cup of bone broth with lunch. So I'm getting a glycemic and as well glycemic very important for detoxification as well absolutely. The joints is very powerful. Yeah okay so what about the other things that we care about like sleep and brain performance? And how how do you? How do you help people address sleep and sort of maximum mental performance for we could tackle them one at a time but sleep is pretty straightforward? I mean we know that you need to be an dark environment in new needs to be silenced and typically it needs to be a low temperature. Most people can up. The room is shades earplugs basically but there are a few of nitty gritty details. Like for example. If you if you use something like one of these new Pads that you can use to circulate cold water under chilly. Pat Healy powder raising. I set mine at fifty five degrees. I sleep like a baby if I'm travelling like here. New York's sleep with the windows open all night. We're here in a month is January so the room gets nice and cold. It will dip down into the fifties and it's it's perfect but very cold environment. How's your wife? I'd makes her snuggle up But chilly pad actually has a his and her side right so my size of fifty five Turner side on actually but the The other thing. You were wool. Socks and wool socks actually causes Basil. Dilation that helps to cool the rest your body while your feet stay warm hack even if you don't have a chilly pad or very cold room and of course if you have a late meal or late exercise session figure out a way to get yourself. Take a cold shower. Go for a walk in the cold brisk weather. You know do a quick cold soak up into a cryotherapy chamber one of those fancy gyms but figure out a way to decrease your core temperature before bed all the more if you've exercised hard or eaten a lot of food within three hours prior to mend time that's one thing is the actual core temperature. Pay attention to the bedroom but also the sleeping surface breathe ability. How my wife's ACA? She likes it hot. I like to call chilly. Pad which has improved their marriage saving yeah And then with light. You know a lot of people know not to look at screens now. Like like you know. I think that's pretty common knowledge block. Glasses don't start a computer screen or if you are where your blue light blocking glasses. Put your phone in night mode but a few areas where it will to two in particular. I think could be better paid attention to number one would be when you're in your bedroom at night. Maybe take off those glasses or he'd get up a you know in the evening to go. Use The master bathroom or you turn on the lights in the master bedroom. You're just basically getting blasted with all that same light. You were trying to restrict from your restricted screen usage. So what we did in our room. Our master bathroom kids bedroom and my wife's and my bedroom was. We replaced all the bulbs with red incandescent bulbs which simulates something more like torchlights sunset. And so it's you. Don't get that big rush of Blue Light. If you happen to get up in the morning and use the restroom and not that I would ever get up at night to take anything out of the but just in case something like that were to happen. You open the refrigerator. Big Blast I you know the the the blue light thing really that becomes a rule when the sun sets and whatever area the world you happen to be in souvenir making cleaning up the kitchen after dinner eight thirty PM. And he opened the fridge over and over again just getting blasted blasts. Yeah so I got some of that. Red Light tape and I covered the light in the refrigerator with some of that. Same Red light tape that restricts the refrigerator fast there's a book called lights out or eight years ago about how they develop lightbulb. What's the beginning of a lot of chronic disease sugar and T S? Wiley sheep shows through. Survival has called. Yeah it's a fascinating book anyways though. So so that's one thing that is your actual light bulbs and and what you're choosing for. Lifebuoy like red incandescent for that and then the other one is the fact that your Circadian Rhythm Sleep Cycle doesn't start when you're getting ready for bed at night starts in the morning when he get up and so getting as much natural sunlight or even blue light as you can in the mornings what I do in the morning is I think. Okay let's simulate. What our ancestors would have done but at the iphone or any foul. I would have gotten up I would. I Seen Sunrise Riot. So yes I will not be opposed to looking at screens looking at the phone etc but I put my blue light blocking glasses on in the morning so everything. I'm looking at is kind of red like the sunrise and then typically around seven or seven thirty. I take those glasses off and all of a sudden I'm getting full daylight. I'm getting full blue light from the computer screen for blue light from the IPHONE. So I'm jump starting my circadian rhythm right time of debut. Ease yourself into you. Put The blue light blocking glasses on in the morning. Then you take them off as you get around seven seven thirty and then you you let yourself get exposed to blue light and computer screens and sunlight and everything else so you blast yourself with light in the morning and those are those are A couple of the biggest for light and for cold and then for the silence piece foam earplugs get a good. I like an APP called slipstream. Dj has got white. Noise is Scott Brown noise Based on some research at Stanford apparently pink noise is the best Faraday. Pain is also up there with things are going and Faraday. Yeah so So yeah there's silence piece is a little bit easier to wrap your head around and then finally just the last thing similar to eating activate your para sympathetic nervous system. You Know You you know Dr Andrew. Weil and I interviewed him on my podcast and he talked so much about four seven eight breathing and I actually do. Four eight breathing. I find that seven. Count hold when I'm breathing myself to sleep at night is a little much but so I just do four count in Alec. Pause at the top eight count out and I can low my sleep latency because I use the or ring to measure my my sleep latency about three to five minutes. It's pretty literally get in bed. Four eight breathing and I'm out like a light US great. Yeah that's great for that. Means you breed insulated county. Four thousand read out for A. I mean speaking of longevity just having long breath out what it does it train. Co Two tolerance about your body holds onto more co two and we know all these long lived animals from the bowhead whale to the naked mole. Rat they all have very high. Co Two tolerance soup. You can breathe through your nose when you're working out when you're out walking you can take longer exhales than inhales you can always be cognizant of breathing out longer and more than you breathe in. You can train yourself to enhance longevity through co two. Tolerance was fantastic so boundless is full of all these amazing tips hacks and tricks and actually incorporating the science into practical things that you can do every day to perform better feel better live longer. Sounds pretty darn good? Yeah it's going to be. I think I think you're getting a copy. I think if you don't have to get one but if people are listening in our occurs them to get one it's I'm pretty proud of it. It took a really long time to write and I tried to make it practical but I also tried to weave in a lot of the sexy stuff like yeah. There are like four thousand dollar biohacking tools in there. And there's you know crazy supplementation protocols for microdosing with psychedelics and plant medicine journeys all the way in the one stop shop the basics so so it's kind of a little bit of everything so you basically taken all the things that people are hearing about in the news media on blogs and you put it into a coherent book that people can follow re look at the science behind what. I'm sure there's tons of references. Made a made a huge webpage for every single chapter. So when you read it. Chappie go to the web pages. Got All the books all the articles pie everything you can use it to get deeper dive into anything. The spend discussed within the six hundred fifty pages for all four hundred. Fifty pages got cut from the book. All those on the website too. So I I pulled out all the stops on this one. Everybody go to Boundless Book Dot Com to learn more about boundless upgrade your brain optimize your body and defy aging been. You've been an incredible guest. I learned so much from you and I think if people pay attention they're gonNA feel better look better live longer and I have a great life. Because that's what it's all about. It's not just about optimizing your Mitochondria. The whole point of this is to live a joyful connected meaningful life and it's at such a good point. I mean you and I I think we both know. There's there's one hundred ten year old cigarette smoking Jin chugging grandma's somewhere in Sardinia who are necessarily living the model of perfect health. We would define it by Western longevity standards. But they're happy they have friends they have a wonderful socialites. Although there probably part of the one or two percent who can smoke and drink and live wherever I would imagine that means. They're probably turned on pretty pretty. Dang it's so exciting exciting to live in this time because the science is advancing so far and the and the average person can actually take advantage of the Science. Unfortunately most healthcare is not focused on this or focus on disease. You're talking about how to create optima health. And that's essentially what functional. Medicine is so as you're talking like. Wow this is really You know awesome to hear you talking about the principles of functional medicine. The way that are accessible people can get to and transform your life so thanks for being on the Doctors Pharmacy van will and if you love this podcast please share with your friends and family on social media common. We'd love to hear from you Subscribed wherever your podcasts? And we'll see you next week on doctors farmers. Everyone is Dr Mark Hyman. So two quick things number one. Thanks so much for listening to this week's podcast. It really means a lot to me. If you love the podcast. I really appreciate you sharing with your friends and family second. I WanNa tell you about a brand new newsletter. I started called marks picks every week. I send out a list of a few things that I've been using. Take my own health. The next level is can be books. Podcast research that I found supplement recommendations recipes or even gadgets. I use a few of those. And if you'd like to get access to this free weekly list all you have to do is visit. Dr Hyman Dot Com for slash picks. That's Dr Hyman Dot Com for slash picks. Only email you once a week. I promise I'll never send you anything else besides my own recommendations so just go to Dr Hyman DOT COM for sized picks. Pic KS sign up. Free today hi everyone. I hope you enjoyed this week's episode. Just a reminder that this podcast is for educational purposes only. This podcast is not a substitute for professional care by a doctor or other qualified medical professional. This podcast is provided on the understanding that it does not constitute medical or other professional advice or services. If you're looking for helping journey seek out a qualified medical practitioner if you're looking for a functional medicine practitioner you can visit. Ifm DOT ORG and search. They're fine a practitioner database. It's important you have someone in your corner who's trained. Who's a licensed healthcare practitioner and can help you make changes especially when it comes to your health?

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Find Out Exactly What Your Genes are Saying About Your Health  Naveen Jain & Ally Perlina, Ph.D. : 714

Bulletproof Radio

1:00:35 hr | 7 months ago

Find Out Exactly What Your Genes are Saying About Your Health Naveen Jain & Ally Perlina, Ph.D. : 714

"Stage High Foam? You're listening to bulletproof radio with Dave asprey. Today's show is going to be really really fun. It's Navene Jane. Who is the founder volume and has been the show several times? This is the guy who cracked the code of what's actually going on inside your by inside your gut. My Gut was wrecked for years when I weighed three hundred pounds fifteen years van. Every month. Because I had toxic mold in my home, which gave me problems with sinuses, all kinds of stuff, but eventually to actually see the data about phages, viruses and fungus, and all those different bacteria. This is the guy who's groundbreaking company Viacom, and by the way to full disclosure. I am an early investor. One of the first advisors in I've just been the biggest cheerleader because this is the data that I- quested for. and. What I found out during superhuman was that I could quadruple the number of species of bacteria in my gut. How did I count them? I used volume of course but today we're gonNA talk about some brand new staff and I've got a new name and a new face for you. WHO's a part of? An Jane the CEO founders here, but also we have alley per lena, the chief translational science officer at Vm, and Allie is here in order to really share the deep science as assistance. Biologist Molecular biologist with knowledge about human genetics and the clinical side. This is one just actually looked at my poop. I'm embarrassed to tell you. And we'RE GONNA go deep on Your Mitochondria your. Energy Pathways Your Silas res-. Your Age, all these new tests new data things that are available. That weren't aborted before, so both of you welcome to the show. The plus you know what an honor and pleasure just to see your smiling face and I got to admit that Kubin hair looks good. If you WANNA keep that look at. Keep that look. I'm? All could. I knew I should wash it. Now, when do I get to get like a heroin? Microgram test V and tell me that's probably already coming out your Muslim. Secrets anything else take a TUFT. So interestingly, if you look at the stuff and seeing our goal, our purpose. Really used to digitize the human body to really understand at the monocle level. What is going on, and what is interesting I think Dave. I think I'd remember full years ago when I was studying while and we sat down together on our last. Portable podcast and we talked about it, so you know they're only three types of genes that are expressed the human body, your country genes that are inside the sal of Newman Sal. Obviously all the human genes that are expressed and microbial genes, and what if you can look at all of them and start to see how this system approach to how each one of them impacts each other, so how microbiome impacts what's happening in our human gene expression and how they back? What's happening in the my took on gene expression? What how Mike microbiome might accordia genus presents are connected together. Together how to biogenesis changes the standard response to things, so my point is, it is literally everything is connected, and for the first time in human history we have a chance to actually look at all of that and apply the AI and machine learning with not just look at the wonderful step to actually out what to do about it and I'm just so damn excited to finally there did. A lot of listeners know about your background at Navene, but the idea that this is your seventh company. You're on the Forbes List and you're exceptionally successful. You don't have to do ups ever again. You just do these because you like changing things and disrupting and in creating so Those things attracted me to this. The other one though is into Los Alamos National Laboratories. Laboratories and you got two billion dollars. Worth of new weapons grade are in dion identifying things is that what if I took that? And I turned it around from like a fear based responses had now. It's just data gathering at a high speed, and it's not about sequencing genes out which has been done before, but it's about looking at what behavior of things is doing. With Arnie analysis. so. That's kind of a quick introduction, and even working for three years with Alli and four years now. So it's. It's one of those things where companies start out your small. This technology and you're doing this one things the gut, but I've been excited I mean you you? You've Dave this new staff coming in like I'm going to be the first person to see it right at least one of the first, but all the same time. Macondo function immune cell function biologically age I stress. What do I have to send in besides my poop for you to know all this? So basically. The it a few things are human body is like a donut to that goes through excite and are caught. Is What is you can analyze at the top of the two? And I'll taught is what if you can analyze at the top of the two, so you look at your saliva, and what if you can start to analyze all the auto microbial activities and I'm GonNa. Tell you something here, and then you look at the bottom of the tube and you start to see what is the all the gut microbial activities that are going on, and then you look at the other side of the two, which is the host that humans and you start to look at it and say what are the human gene expression? Expression that are coming along. What's the my two gene? especially that coming along so in this cast the health intelligence. Test that actually you can do today, so it's not Sunday in the future may come out. You can go to dot com right now, and you can actually ordered this desk, and when you order tests for the first time you're going to start to see the schools and insight that are all tied together, so it's not this comes from microbiome discounts from Mike Akande discounts from it is all tied together so in a sense that. When look at your biological age? Biological Age is not somehow you microbiome doing something all yourselves doing some failure I took. It is all integrated approach to what makes you edge that means you may be chronologically, won't. Like me, sixty one but I am biologically only forty are. If you ask my life, she thinks like a twenty five year old man, but you know they'll just. Different for different people right, but really is that we all eat very differently, and I caught was what if we can start to measure them at Molecule and cellular level? So, we stopped to look at immunity that big thing in this world of you know before it used to be all about flu, and now it's all about Kubat, but his wife is it. The some people catch exactly the same widest, and they have almost no symptoms and some people end up in the hospital. What is the difference between the two people? It's not the gene somehow different, you know we all have one thousand nine point eight percents theme genes, so it's not genetic. It is is literally is harder the immune system response when they get infection visit, get this package and how the immune system primed for right. Is it much inflammation in the body? Because you obese, you have diabetes, heart disease that means you have inflammation going on in your body to bend the and then you inflammation. Going on immune system is too busy trying to take it on what you already done. And now you hit the less than used art I'm done. and. It just gives up and suddenly you have all these issues and axel, what if you can build immunity at the cellular level, and so we literally now give you your immune system health. We give you mind to quandary of health. We give you your salary health and they're going to describe what all these different things are. What's included in them? Including at the deepest level every pot way that goes into new calculating your cellular stress, so it goes into calculating your. Mitra Connor biogenesis and not just tell you what's going on, and then here what you can do now to go take care rather than some generic advice which I think, we're most people. Go wrong this. The Oh, I think I can just stay. Thailand because I think I. got this free radicals? A lot of our west I think I'm going to do to. Without understanding the glue to tie in has very high amount of stuff in there, so if you have very high style, five production in your gut gag, probably the gluten, not be the best one. Maybe you need to take control, but the point is, it is different reasons for different things, and then you have inflammation. It's not going to take some anti. Drugs but A. What in anti-inflammatory supplement so I'm gonNA curcumin while the point is, you need to understand what is the root causes of that inflammation. Is it coming from cellular stress? Is it coming from pathogenic infection? Is it coming from some? Mental Stack talks in the more boxes. If but if you don't look down, the line of that is, you're going to just do things that may actually end up harming as systems biologist as a systems thinker and a computer hackers means your system's thinker as well for my my background. How often is it one thing that's causing inflammation? Betty really is not just one thing. It's always the combination of many things that actually come together is literally unless you have infection only used to. That's one major thing, but in general, there are a lot of things that really come together, and while men the food. We eat the lack of nutrition that we don't have I mean literally. The inflammation in the body is in fact without inflammation. We will not so my point is not that people somehow think inflammation is bad. Inflation happens because it saves without inflammation. We won't be deemed right so yeah. It's the wrong flavor at the wrong time wrong version. This is absolutely not wrong I just wanted to add that the. When you have one thing like a bad virus, it can cause inflammation sleep. Okay, sometimes you can point to one thing, but what pathways are GonNa be turned on as a cause of that as a result of that causal one thing of inflammation, that is where it differs from person to person so from some people. People you will have a great. You know antiviral response, and then you are system will know when to actually stop itself and be like okay. We've got this taken care of their specific of breaks on the immune system that we know offense, some of these breaks like p. deal, and other things that are targeted by immunotherapy are the types of genes that we can see, and then for some people be uncontrollable inflammation, and once you have. have specific types of site a kind pathways turn on if they're not controlled Weldon, they keep recruiting and recruiting these immune cells, which can even lead to site, a storm and things like that, so the different pathways that go and and trigger. That's thousands of things going on, but the cost. Sometimes it could be one or two really sort of culprit type of items, but as Navene said it also depends on your lifestyle, what? What you've been up your press that in thirty years. What you eat, that will determine what are going to be those pathways once the virus. You know what comes in what are going to be those pathways that will be turned on and based on that you know what the to support some of these anti microbial antiviral type of responses, or you need to actually make sure that you tame your immune system at the right diamond stage. For instance, let's say that you've been living off the standard American diet with tons of corn, oil, soybean oil all the inflammatory oils, so that actually the fat in your body is made out of those kinds of oils, which is what happens when you eat that way. And then you get kind of random virus that's going around. That has You know one percent, death, rate or something like that, but you're really sick from that. I gotTA wonder was it the fats and your diet, and the fact that you primed yourself for mass inflammation. That was the cause. Whereas the guy standing next to you didn't eat. That way didn't have any symptoms, so was it the virus? Or was it the lifestyle or visit the system and they kind of know where I'm going with that, but yeah, it's it's. Cool Morbidity. If you notice that how many people had catch exactly the same flu? The same dismiss tedious thing that somehow people think is going to kill the universe. Right that mysterious thing. Of Young people they don't even know the there have infection because they just literally to use with that right in other people who have a whole bunch of other cool morbidity. Signals like so they have diabetes heart disease, there have obesity. They got all types of things going on in their body, and suddenly they may catch flu, or they may even smallest off things, and the next thing than a boondoggle ended up in the hospital. Right and that to me is really the key. Is that your immune system is your body actually? Aw essentially are. Being through this situation that you August second to fail because the literally at the cusp of feeling. When I weighed three hundred pounds, I had that chronic inflammation, and if I got anything Oh Jeez, in three days, I been have another sinus infection, and I would always go down inflammation pathways and I figured out how to turn that off but part of that was lab tests very expensive, weird lab testing Oh. You have too much. I L, six or too much of this other inflammatory kind. And, it's been very hard and expensive to quantify that and it all does in my world. Come down into the day your Mitochondria, but there is no solid mitochondrial test out there I've I've tried every one of them We've got one at upgrade labs. The only one that I trust until you guys just came out, were you? You ride a bike with a special algorithm. That's exclusive to US where you look. Look at how well your body use oxygen. That's the output of the system right? Generally this many this much energy, as we measure it from your legs and this much oxygen, and we'll tell you the percentage, but we can't tell you a whereas all that stuff that you're leaking. Where's it going? But you guys are looking at what specifically run maddock Andre in your test yet. So I'm GONNA at have Elliott described. Major box to that are the might to be at how one is the microcosm deal biogenesis that means how well your itself is recreating reproducing because unlike the Salad Division that only happens when you divide the south, the remember the mitre cordray used to be an is an organized been inching bacteria. It is constantly dividing and contract degenerating itself. So how'd you Magid? The might quandary. biogenesis has never been done. Dat is the one that constantly stout does the Saudi appear that the end of the year the oxidative stress and you know, but it's adolescent automatic on taxes dealing with that, so that's one thing the second part of that you talk about. He's most people think my country as energy production. Energy, production, most people think of my country as ADP side of the crap site. Right that thing that is what the Michael country is about what it is moving a lot more than that and literally. All those parties, so Elliott's. You wanted just Geico for the second year. In this talk about all the things we look at what causes the my to conduct biogenesis. How do we look at things? How do we recommend things? What are the things in the eighty production to just geek off for a second year? So that did knows that you actually know your staff your molecules. Time my second. So let me try to break up. So some of the things that that you said you might have. Is An energy. A furnace is the energy generator for the cell, and that needs to rise up and actually deliver that energy at any occasion when we need more of it when there's some kind of demands stress. Maybe you're fighting something. Maybe you have in not enough of the types of nutrients, so a minor contrary actually can sense when you don't have enough energy. From something. Let's say cold. PK that senses the ratio of amp to ATP. ATP is that energy molecule and we get ATP from my Andrea so might. A country has a way to know about this, but to know about this. This signaling pathways need to actually tell mytalk Andrea, hey. We don't have enough energy. So can you make some more police and for that? You need to have first of all enough. Might Andrea and all of the? The compartments and components of it, and they'll the proteins they need to be functional so when a cadre knows that it needs to produce more energy or metabolize certain things for you for the cells there is a master regulator of Mitochondrial biogenesis called PG C. Alpha and this gene is what signals to might a cadre to be able to function optimally and to actually deliver what the cells need, so that's one of the things. Things that we measure that can be in response to different stressors or just the ratio of amp to ATP. The Energy Molecule for people listening going home I just got lost their so ATP is a Denison Tri Phosphate so this is the energy molecule and it goes down to ADP when you use it, and if everything's working right, it goes back to a teepee, so it goes from three down to two down to three and a MP. MP is what happens when something got screwed up and now you're you're busy. three-part engine. You just lost the first part. And they lost the second part, and you've got an P. An p you either pete out which biologically expensive valuable molecule just got wasted your urine, or if you can get enough energy, you could rebuild that in reuse it again and if you're good at doing that, you'll probably live longer did I. Get it right. Absolutely arts checking excellent good now. Everyone learns amp ADP ADP in that order like one two three. Okay going try. Yeah, exactly exactly so in response to. Activation PG. See on L. A. Now for. Could you see one of activision? Might Have Andrea is news to. Crank up its functionality basically, and in order to give you the energy need first of all you need to get fuel which can come in either a carb or fat sources, so it comes from. Let's say long chain fatty acids. Depend types of fats they need to be transported into the minor country before they can even be processed, metabolize oxidise and for that you need. That's why some people need some help with that. They need L. Carnitine. That's one of the reasons they might. They might take that. Other sources glucose in glycolysis does a very well known pathway where you break down different sugars, it's more than just glucose that can come into the pathway. You can get that pathway activated with fructose, and with breaking down of more complex carbohydrates, but the point is then you get to the Krebs cycle and after the Krebs. Cycle sonus the the TC cycle, citric acid cycle. You are able to generate some of the molecules that then also contribute to electron transport chain, when as a series of different transformations you finally get the most of the ATP pump tart through the pump. And you need all of these different components. Now all of these components in a decided chrome see there is a ubiquitous on ubiquonol shuttle You need to know what our personal gene expression pathway profiles that you need most because if you just you know if you take everything, some of the things may not be very beneficial for you. For for some people you may not need L. Carnitine need you do not need any more of the protein and Amino ammonia sources in in your body, whereas other people more of the CO Q. Ten. Important my statement, look I take one hundred fifty supplements a day. and I've just people say well. You might be wasting money. I might great I'm happy to have the world's most expensive. I have no issues with that what I don't WanNa do is I. Don't WanNa. Be a situation where I'm taking something that doesn't actually benefit me and I finally figured out after a while of I take too much acetyl l.. CARNITINE which is in a lot of cognitive enhancement formula, but not everyone needs it and not even everyone with a optimized. Metabolism like me even needs it when I take it I actually a little bit of a headache. I jot tension, which is as side effects I have enough Acetyl L. Carnitine in my system, and it actually doesn't work it. It Raises Manziel Colin levels more than I need. So how would I know that 'cause bio hacker? How would someone who's taking that? Going I have had all the time and I'm grinding my teeth. Will you just wouldn't know it and so some? Some supplements in access are not going to help you and my people's Dave. Tell me what you take like I'm not telling you what I take. Are you former three hundred pound guy who had autoimmune issues? Who was my age? Oh might you be one hundred fifty pound woman and a different age? Just don't do what I do, optimize and for me it's been an evolutionary process with a million dollars, and what you guys did is said it's been two billion dollars. Of basically military spending plus all the research you've put in over the last four or five hover enrolled. We are now. But all of that and saying okay, there's a way someone can get the test and then say oh. These are the things that the gut bacteria plus the combination wind bodies. Actually doing that's going to tell you the supplements with the highest. Roi and care about is our way. This show is based on our way. Right, yet you listen to the show. Was it worth more than an hour of your time? If so give us a four star five, whatever if not done? Every time I listen to your show. It is one of the best auto I I get I think they're very very few people I. Honestly believe deliver value every time with every guest. Bar, not I mean they literally what I find it. You talk about actually learning and learning the valuable life lessons something you can take apply I would give that a five star everyday. Oh, thank Thanksgiving, that means a lot coming from you and Elliot I know that you can. You can pretend like you're listening to get. You don't have to listen. I actually I'm on your website. On? Thanks. What do we do I? GotTa tell you that? Some of our best people that'd be hired have come from people who listen to our guests to get crew. That's that's fantastic. But what through that by Andrew? Yeah I was going to speak you. One step further and going to announce something that I didn't want announced, but now that you brought it up. Actually just launched this health intelligence service now that actually looks at. You might do corn real gene expression, human gene expression end the microbial genetics person, but got altogether. And KNOB! You're going to be absolutely launching the preseason supplement designed and made to order for each individual after due to the test when. We say you need twenty two milligram lycopene unit eleven. Need Seven Donald Elevate and literally made those capsules. It capsules whether you need thirty five games when you need sixty. Me Made. Them for you on demand for each individual completely made to order you. That will be launching on August West. That's right. That's pretty stoked to see what you guys think I need to take causes I'm like as it can be accurate. I think. I think it will take science, but will it have that weird Japanese ingredient that L. Cam, five, five, six, or five eight, whatever that was probably not I. Think there's room for tweaking on top of it, but you're gonNA get everyone's. Major categories and if if you're a weird bio hacker like me and you. Take this cognitive enhancing, as you can still play, but get your bases covered. How much magnesium Tony I don't know like you tell me. That's what I want. The Our job is to look at ninety percent of. That you give you everything you need and nothing that you need. And then you go in their own your own and actually do the by happy. You literally personalize even off that. Because you know it doesn't matter how much we learn. There is so much in the human body still going to so as we get millions and millions of people doing it is going to get better and better and better, and just the someone else be able to improve. That goes down in, but we're not there today so I would be absolutely telling you that today you can do that. Maybe four years from now is going to get more and more difficult because we will lo every by that. So I guess. Yeah can interest say why we call it precision in precision supplements. In further precision nutrition. Canadian say why we call it. Precision in a precision supplements were referred that way with nutrition, because nowadays. If you look at what people mean when they say personalized nutrition of personalized supplements, it's more categorized than it is personalized. It's there is the new new tropic category. There's a weight loss category. There's know insulin category there. A performance, endurance whatnot, category, the cardiovascular health category, and then if you actually think well I need that support to this debate now, just prophylactic. I need improvement in my this then. Then you cover all the categories are going to end up actually with five hundred supplements for all you know, and that can be harmful, because it can overload your even your liver and kidneys can be overloaded with this. Bless all of the things that go into supplements that sometimes contain heavy metals, and when you add up to much of that, and then all of the fillers and things like that so How do you the narrow down to what you need and this is when you know it's. It's A. A way of personalization that is based on molecular level precision, and you can only get molecular level precision if you can understand you know system wide, what is actually happening down on a molecular level to meet your molecular needs? So if somebody needs more a deep loss, precursors in order to fuel your electron transport chain or your Krebs cycle than that is what you need, then you can take you know nicotinamide right beside or or other ones or if you need more of the UBIQUONOL in order to. To to fuel the UBIQUONOL beacon on shuttle inside also the Mitochondrial, or you need more of the L. Carnitine, some people do and so with this molecular level precision, and also looking at what is going on, you know in your micro Byrom, what else is happening in terms of your stress, response your inflammation, only then you can make these molecular precise supplement recommendations and or food recommendations, and so for recommending any one thing so like cokie and orders a burglary in for instance if you recommend this one thing. Our philosophy is that you look at what a person has gone on all of these different functional levels, integrative and functions are painted by all of the different activities of of the pathways and microbial contribution. As well you look at what is going on integrative and the ingredient that serves most purposes for you to kind of re adjust and fine tune those knobs in for the fewest number of ingredients that is what's going to give you that personal level of precision. So that's why we kind of you know. Take the systems approach to give you this functional integrative precision supplement precision nutrition offering. It makes it makes so much sense to be able to do that I'm I'm excited but I have a question here. I feel great. When I take my stack of supplements and outright, tune it on a daily basis I can know what I didn't sleep that well last night. My Oral Ring tells me as much. I feel like or like you see a little bit puffiness around your face. Okay, whatever I had for dinner last night didn't didn't always work. so. All, right I'm take extra this in less of that there. There's a daily tuning, but if I was to say, run the health intelligence. Test Tomorrow and I've been taking this stuff. Wolf is evolving stack of stuff for twenty plus years. Isn't Arthur results going to be based on my supplement stuff, and then if I quit taking those elements and I started taking something new wouldn't have to get a new test, but This is all about snapshot of what's happening in your body right, so we look at for example, your system and signal in terms of what is your histamine signaling you right now, so even though you're taking supplement to actually maybe take care of it, but the signaling is still happening, so we look at history minutes to s signaling. We may be looking at your. Prostate, Glendon bio synthesis, we are looking at all the tissue remodeling and repair so good healing is very interesting. Is that you know? Obviously, the body's designed that in case you get wounded, it releases things like Combo sites and platelets who take care of it, but what happens sometimes the people have this mechanism turned on. Even today's no wound, and the body's constantly producing data stocks. Get really on for me. Look at the or kind signaling. We are looking at antiviral antibacterial response I should be looking at all of those cigarettes to figure out how your immune system being activated, and even though you're taking supplemental deal with them, but the fact is the activation. This could happen. And that's how we know what you actually need. So then the the idea would be that someone comes in. They do the health intelligence test then they save so much on the supplement. They're taking because now. They're taking the ones that they need. on subscription, and all of that that they can actually get another task in six months or a year and sort of see. How's it working and then tweak? Do that it's included. When we launch our supplement attest was included. Okay would. You do the the actually do the test. Look at every inside your. Sites in the body then gives you the preceding supplement, and then send you the another test for months or six months later, and then reformulate and Redo. The things again soon. Sense that you're constantly seeing what is going on. We give you what you need to do, and then prove it to you that it's working and tune it again and then we keep keep doing another test of Youtube fast. Youtube and the idea is keeping your body in that optimal fees. Keep retuning your body just like Nutri new car every year you read unibody every piece for five months. I. This has been sort of every bio hacker's dream, and frankly most who are aware. Wow, I didn't have enough magnesium or zinc or something last year and this year. I, probably do so, what needs work now? the it's been a real pain for me. I have a directory on dropbox or something full of all my different lab tests going Oh what's my. Level of red blood cell, this and plasma that and it becomes a little bit overwhelming especially for a I'm just a mere mortals who aren't a professional bio hackers, so the idea that it's an kind of an automated system or you send a sample every now and then, and it's an it's built in, and it looks at the system of your. God and your oral microbiome in your cells that to me is one of the most attractive things you have spent. Countless tens of thousands of dollars on that's getting disrupted replace so that's you know. Go Go van. And Tesla developing is going to tell you that. The most of the most of us, we look at the symptom. We read unbeaten start to see some symptom whether puffy face or something that symptom, but we don't know. Please symptom. The thing that are going on inside at the cellular level likes so for example. We all know the cellular stress always going on, but is that cellular stress coming from oxidative stress? Is it coming from genotoxic is Hyprocrisy induced interest. Is it anti oxidant expressed the so my point, exactly what he's offering the celery stress that's sooner or later is going to end up showing you the symptom so if you can prevent it by actually big the. Action earlier you don't you don't even notice it. That is, that is the dream, so you don't know the bullet that you dodged. And one of the things that that's fascinating to me is is you're talking about all these different pathways in alley I have a specific PG one alpha question for you to go back in the interview. so I am perhaps the world's biggest and only PG, one alpha of and boy Tommy a little bit more about what PG one alpha dozen the body forest. You're spending more time at home now, which means more exposure to junk light from indoor lighting and led screens until now. My company true light is working with the people who lit up the International Space Station to bring you and your family true circadian lighting in a single data nighttime bulb. This patented technology is a game changer, because it emits the critical and healthy sky-blue spectrum during the day that your is need keeps you energized and focused, but it ditches the toxic parts of the blue spectrum. Get beamed into your brain when you're indoors today under normal lighting at night, the neutral lightbulb. lightbulb sends out those warmer wavelengths of light like sunset colors that signal to your body. Hey, it's time to wind down and get ready for a great night of sleep. This neutralize bowl was called true life Sir Katya. You're stuck inside now more than you like. Make your lights work for you not against you and feel the difference. Go to shop true light dot com, and be one of the first people to get this major upgrade. That's shop through light dot com. Then the signal to. Support and build up more of the Mitochondria, so might Andrea. It's not enough to just produce energy and to crank out this electron transport chain. You actually have to produce more of the building blocks of the Oregon L. and you. Know How to Be ready to make more medical. Andrea, so when cells need to divide when you actually have more Mitochondria within the cell, so all of the different pathways converge, and then diverge through PG one alpha, because it's a master, mitochondrial regulator, and yes, of course it does stimulate the metabolic reactions themselves. Even the you know glycolysis, t cycle enzymes they get induced in one way or another through PG one Alpha and people are gonNA and other type of transportation factors signaling, so it's miracle. Grow for might Oak Andrea so you have more of them, so you can make around Matt. How do you raise it? So. There is a whole number of of supplements that actually raise the expression and activity of PG see Martin Alpha the point I think is. How do you pick the one that's right for you so actually? Some people it. It almost makes it sound like. Did you see Alpha is great? Therefore everybody should have more of it, but the thing is if you have. Have too much of this might have conrail activity. The byproduct of the is reactive oxygen species, so if somebody has enough of the metabolic TV and they have oxidative stress. Then you don't need to stimulate PG see one alpha, so the point is you know I? It depends how you ask the question. Is it like a miracle for everybody and we should? Should we should then have more of it or not. So of course there are a lot of supplements and herbs that have specific ingredients that will boost your pg one alpha, but you may want to actually concentrate more on the reduction antioxidants in detox type of pathways because your Mitochondria already performing performing so well that as a byproduct that's making these. These reactive oxygen species dip can then damage my membranes of might Akande itself and of your other similar organized to the that's beautiful. Your environment is polluted or fertile enough, and you pour miracle. Grow on your Mitochondria. You're not going to get what you want. The things that I was hoping you would say that. Exercise is one of the easiest ways. To by the F. It is to exercise is one of the best way to increase the Pity when Alpha. In fact, it goes to I. Think Induction of EMP acted, and Pika activate I it. It does now. What's is another thing that's not coffee that raises PG. Went Alpha as much as exercise. Their some polyphenyls cannot coffee, but some herbs and polyphenyls specific ingredients that raise beach. One Alpha I mean It depends which one is best for you, so it could be like Feis attend that you can get from strawberries or could be you know. Moreover new in your trophic effect depends on what you need. Family, it's a hint. Listen, on his Team maybe I wanted. Nicotine Nicotine is one of the most potent ways to raise P alpha. Here's my question. Are you guys? GonNa? Tell me to start using nicotine nonsmoking. Smoking's bad but Nixon repeatedly went off, but that's why everyone gets thin and looks rift when they smoke and eat a bunch of crappy. Even I don't recommend you do that, but as nicotine could be on the list of things to attention to. What? Think Nicotine but. You guys are GonNa to tell people to start using it. Asa. Did we do look at things like trump visit metrology? Boost EC one who'd be. in a solid acid, so question equivalent, but lot of different ones that can actually support at the DC our for through different mechanisms, so I would see. Yup, the exercise is really good for there's no doubt about it. It goes to the induction of advantage. It induces the EMP activator. MPC activators I. You can look at the things around. Are the things other supplements including nicotine? If that is something, you are willing to do so. Yes nicotine is one of the things that actually does add. There's no two ways about it doesn't increase the PD Salema Alpha when Arthri. If someone smokes. What are we going to see in their? By on their microbiome, their oral by or there might have contra just a counterplay so actually BBC still smoking, and by the weeping and lot of other things have clearly shown to impact significantly their auto microbial activities. In fact we are, we have five with FDA, and in fact we should be expecting next week with a breakthrough device status with we are even to show that autumn. Microbial activities determined the stage zero any stage, one OUGHTA cats and be actually show that how? So we literally can look at pre malignant and the stage, one auto cancer just by looking at the auto microbial activity than we should. The people who actually smoke or people who are chewed tobacco or the people who are in fact doing listerine or whole bunch of how especially ripping beeping quad is a massive massive amount of changing the auto microbiome, and you start this mysterious disease that people are talking about. People were whipping in their lungs that that click coming from auto. Auto microbial activities being completely change rather than some mysteriously that disease. What's coming while I? Just wanted to say that it depending. It depends what you're. Metabolic reactions are GONNA lead your nicotine to do so you can have more of a like a niacin input, or you can have the nicotinamide right beside precursor, which then goes to and D-plus, which fuels your energy, and we can see the enzymes, the genes that code for these enzymes that convert any D to an. Eighty plus an ADP and ADP, all of these different three dogs, reactions we can see those are active, and we can also see in the microbiome if nicotine nicotine made. Nicotinamide pathways are activated by your microbes, and so microbes can actually give you some energy. They can even do some detox for you. They have their own glutathione S. O D in Catalase, and all of these things, and they can also give you some be six or twelve, so maybe you're getting already a lot of between all of you don't need anymore, but maybe you're. microbiome can help you with a little bit extra. Be Six, which you need to actually make use and produce more Serotonin, so you need to take all of these things. Things integrated into account so nice, and for instance it's not actually doesn't work out great for everybody for some people it can contribute to this positive. You know nice and nicotinamide energy type of pathways for other people just causes a lot of flushing does not naturally convert to ad. It's not a a short path so for some people that conversion actually depends on at enzymes that expression of which we can also see and decline with age. It's so that's another thing that could play into your overall biological age score. I'm I'm just so blown away at all. The different little questions the Niacin before going to sonnet who the heck knows! I've the first time. It took Niacin I was probably maybe twenty eight and I'm. Turn Bright Red, and you'll get hot and feel weird, and it's not pleasant at all and other times. It doesn't do that much, but those dependent and I've done tons of ad and so like okay. Make sure that you have sufficient levels, but being able to be precision about it. I think this is. This is going to really change a lot of people's lives. I'm I'm pretty darn excited about it and the might Oh conroe picture is my goodness. I mean. I've spent a thousand dollars on test last year. Where they took my live blood, I think it was live, they must have been exposed to hydrogen peroxide like you can make good antioxidants and. Good for you and like what do I do with us? It doesn't do anything right, but but good for me. They weren't bad at that. Maybe I should take some more vitamin. C. But it I couldn't do anything with lost two thousand bucks, and I didn't learn anything that was useful, and so the idea of okay. What changes would you make not just for for the the history of Almaz? Change this that you put in your mouth, and you get this in different in activity of what's in your gut. That was step one step to all these other sailor things around the body I'm I'm pretty excited and I can't to get my results in on this. You'll be getting them I. Think I'm GonNa? Send you the kid and you're going to analyze it. Right now so I'm going to do tomorrow. To deal, so this is brand new stuff I I know that I I learned a lot from from my dismay, ones and Ellie. One thing that you you did say earlier about fillers and binders so I I take I. Take in, make super clean supplements, and all blended myself in a blender in hold my nose and drink it if I have to. But. When you guys got my results you. We had a phone call. And I I said well okay. We're GONNA, beginning this P. E. G., polyethylene glycol, and so it turns out. I was taking psalms, and I did a whole blog post. Signs arms put on twenty pounds of muscle and six weeks. I raised my PG. One Alpha beyond normal levels did all sorts of crazy stuff? I'm but They were available in that solvent. And you said you're getting a lot of the stuff, and it's messing up your gotten like what's going on so I looked, and now if I'm going to use arms, I will put them in vodka and use a magnetic stirrer, so I'm getting ethanol base, but that was directly from violent things. And when you say, you can tell you, guys could tell 'cause I didn't tell you any of that. And you looked at my poop, said you've got this going on and change your bacteria, and so if you listen to the show going. My during the changes bacteria, you have no clue and none whatsoever, and there's no way you would, because I eat a really clean. I raised my own animals original earned vegetables. I knew everything to into the soil that went into animals that went into the kitchen. What kind of Cook where I used? The oils came from like I. do everything. And still I don't know all that and maybe I should be using your twenty percent olive oil, hell, I dunno, I think what I'm doing works, but if I can get the data, it's going to be another level for me and if you're probably not where I am because Desmond Your Life's passion. Is a few hundred dollars a and then you're good to go because you've got more data than I ever had and I. I'm kind of jealous. I wish I was just starting to be a bike right now. Because it'd be easier than Aspen. Funded at it as the the fund would be that, what about age you're talking about? Biological aging I'm seeing all sorts of DNA. Powered things was saying I. WE'RE GONNA. Look at t Lamar's. Determine. Biological Age because I think you're different. Yes I. Think I want you to talk about celery stress on when you talk about little bit about all the other things we're looking in incomes of aging because I really think that is so unique that anybody has ever done. Yep So many of the things that we just talked about play into cellular aging and cellular aging well. How do we know that it's aging? By looking at the actual calendar, the clock we'll look at more of the settler markers of that aging clock, so the decline in essential functions of the cell They have specific pathways that signifies that okay. These cells are not coping well with all of the proteins that need to be transported somewhere with the Post. Translational modifications in order to know where to traffic the deliveries. Deliveries is of certain proteins for instance, and then went to take the protein or mis folded protein, and then degrade it so prostheses of ubiquity nation when you target something for degradation processes for correct export, even processes that make cells specific immune cells, pick something up and display it on the outside of the membrane to say that this is like a foreign type of particle or substance. Substance so that your immune system can target it all of these functions they actually can decline with age and one of the reasons is the reactive oxygen species and oxidative stress, so oxidative stress happens when okay you have, those reactive oxygen species, and your ability to mitigate them is actually not keeping up with the rate at which they are produced or introduced into the cell, so all of. Of the things we talked about so far actually, if these functions in one way or another are declining with all the wear and tear that go through than that contributes to cellular aging and two lamas also included, and so this functional progressive decline of the cell is Senescence and cellular aging, and all of these things go into that matter. conjul health obviously very much plays into that. Mean looking at all that mean all this stuff from the seller senator. San You looking a dysfunction of hobby? May Protein degrade protein? You're looking at DNA debt in the damage, the DNA that's happening hobby they repealing regulation of Telomeres oxidative stress while you're gonNA pop doses to see really rb, killing these cells or just essentially going out of control. Right, so some pathways will signify that cells are undergoing programmed cell, death or But if you just have this low enough. Of damage or stress that it doesn't send cells to apoptosis. Just makes them less and less efficient at many different processes and pathways than you have this progressive dysfunction happening the loss of really essential function, so you don't get enough stuff where you need it, and when you need it and signs of that the aging cells as what we can pick up with you know the gene expression that lights up all of these different pathways. that is a very different picture than sort of this one thing is determines how old you are, so I'm I'm pretty excited about that. The one thing that you're not including that I really really like is. is one of these s called the Dynamo Measures Your grip strength, and it turns out that one of the cheapest measures of how old you are. How hard can you squeeze in the digitally measures that but I don't think that's necessarily because I'm pretty sure that the volume age is going to be a little bit more accurate than than how hard can you squeeze? Literally you can measure your Biological Age by measuring your inflammation in the body because the systemic Gloria. Chronic inflammation also causes you to age because all of that causes your cellular stress, so my point is by looking at all the cybercrimes kinds mark looking at all of the systemic chronic inflammation is another great signs of agent. Some people will just look at the nation. Just look at the me. Well guess what? That's just one of the many many things that go into the systems off Egypt Sudan. I think Eddie, said my two hundred one of the big thing, but telomere doesn't tell you how. Is How badly is going? And if you might according to now going to produce energy, you're going to age. That's how you think. and constant metabolic stresses as well can induce oxidative stress and inflammatory response in OCTA and and different aging processes, so it's all actually truly interconnected. That's you know the the systems view and you have to figure out which blaze in the system. You need to act I. was just remembering that the there was a there. There's a set of pathways that people for somebody's GonNa find very amusing from the microbiome that part of protein from imitation that lead to production of sperm meeting and spur mean, and those are byproducts of microbial protein from nowhere. That's. By the way I take, I, take sperm, Edina orally You can get a supplement out of Germany. I've been looking for a long time. I wrote about it in superhuman and yet it Kinda smells like you'd expect it to smell and it. Yes, it was discovered there, i. If you know what I'm talking about, that's okay because you're young and innocent, and you can stay that way for a while longer. The product equality check. Yes, yeah, it's a but it. It is necessary. In fact I take a specific strain of probiotics that are that are shown to increase Birmingham production in the gut and are correlated with increasing your lifespan. So you know that that's a that's a good thing to do and I think that that in fact when I send my next sample you'll probably seething to wait. This guy's the best permadi and I've ever seen and hey, you know S. that's how I roll. Yeah. We'll tell you that. Yeah so so all of these things in it depends what microbes are doing and what the host responses like if you need more of the. Amino acids and protein substrates that will make your microbes give you even more natural, you know. Spur meeting, or you actually have the kind of microbial functions active that give you sperm, and they're more likely to take it and make more ammonia in future scene, which can be toxic and harmful, not even just for the gut environment, but it can also lead through the. Intestinal barrier into the bloodstream, so those different pathway factors can help us in a be more precise and personalized different recommendations for you. I think it's one of the problems that have been out there for while on the Paleo Diet, the old Atkins Diet. And even some of the things like like you get into whole thirty, and another dies like that all of which are infinitely better than the standard American kind of you know random food diet, but it's this excess protein and the ammonia problem. The problem there things I've written about in the bulletproof diet. That's now. A book came out six years ago. I was doing the research about eight nine years ago. Because when I was on a high protein diet, you do that and people have been to a gym or people on high protein diets. There's the reason that it doesn't smell very good in there. Future seen like. Named for what cadavers smell like? There's another one we see microbes so out. Reno was not peterson the smell putrid, but could have arenas there. Thank you. Yes, so cadaveric is more from lysine and future seen as You know our Jeannie. Knock, meeting or meeting pathway. Yeah, so we could see if there's too much sulfide as well which can come from sulfate or sulfite, or it can also come from the from you, acids and sulphur, amino acids, people sometimes overdue on the whole Sistine in different forms of sixteen, which are good for multiple things, but if you have too much of that, the Sofa profile going on with some of the more toxic or pro inflammatory sulfides happening you don't need that, you actually can do better if you substitute for a different type of amino acid or for more but. I mean lasted sources I can in specific types of sprouts and You may even need just enzyme. I'm four Lino to help your protein digestion so that you don't have your microbes digesting the protein, making these harmful byproducts will then cause. Inflammation and oxidative stress in your cell that we can measure from the host side. One of the big things that that's been in superhuman so long as guys. The type of amino acids matters more than how much protein or how much meat or the plant based or animal based is really about these building blocks, and then the peptides. Heather glued together. And one of the things that popped out is the amount of glycemic. The amino acid, the in proportion to sistine or the other amino acids that are inflammatory is really important like most of us are low in glycemic. Say Eat some Collagen get your levels up. Do you guys provide specific information the test about your ratio or the amount of glycemic versus other. I mean losses that are essential but inflammatory. Well, we don't actually measure. The amino acids themselves. We measure the activity of all of the past. Is that needed to? Let's say convert one amino acid into another like the sistine homocysteine Methionine, all of these pathways, and we see genes for that and differential expression between people within a microbiome and your human blood transcript domes, so that gives you a unique perspective into. Into more than just that one final readout of the of the amino acid. You see exactly which routes along your biochemical pathways you're more or less likely to activate and based on that. We want to actually be proactive to to help you rebalance. I'll tell you just one example where something called trimethyl and I'm sure you know, but the T. team G. beaten. It's given different forms. There's a butane HCl which can help your. Digestive issues including protein fermentation digestion on the GI track of things, and there's a beaten and hindrance that you can take for the muscle donor, and and and all of the cardiovascular benefits that it gives, but some microbes will take that trimethyl glycemic, and they will take that into the Matana Genesis or methane production pathway, and you will end up making more methane than you know and methane gas if you it's. It's if it's not really produces is is not an issue, and you may not have that microbial profile, but we can measure in your pathway analysis in your your results, if you have the kind of microbial profile, archaic basically are the ones that are methanogens. If you have them actively making methane than you may not want to look at you, know TM, g may want to take something else for your. They. Just have issues, and if the digestive issues are in a one kind of a benefit from Brahma Lane and Brahmin veloce hit some of your inflammatory, and some even fluid retention type of issues, but if you're just officials are because of let's say opportunistic microbes then back to Bergreen, bring has antimicrobial. Properties and it can also help the back to your am PK and and all of these different metabolic pathways. It can help with that. It can help reduce your You know fat and sugar levels, and so looking at multiple things you need to hit personally and things that you do not want to introduce into your system, because you have enough or can actually be harmful. That is what drives our in a nutrient prioritization for you. That is exactly why we go to multiple functional medicine appointments, and then someone who is well trained as can ask okay. What kind of mission? What did you do beforehand? What do you think caused it? And then okay, let's may be quantified. Some of your cytokines kinds and all and they'll help you to dial in on it and I. Think we're still going to need that for a very long time, but I think you guys are going to get at least half of that. Just because it's the easy stuff out there, and then we'll get the weird stuff. And the more of the test you have the more. The weird stuff becomes less weird because the data sample goes up, this is this is big it's really big in the world of living a lot longer, performing a lot better and just knowing and I. Don't Know So. It's been twenty five bucks on this supplement or this supplement, or neither one, and be able just to make an optimal decision, and so I, I just my thanks. We worked for a long time, but just thanks for continuing to push it and navene particularly. You're not doing this for money. I know you very well. You're already very comfortable. You're doing this because it's cool and because you think it matters and And truly grateful there, and for bringing in people like Ali You know La, being systems, biologists, and having that knowledge in that way of thinking is very unusual. It's missing from Western medicine entirely with there's one drug will save everything and Nike I. What did you see when Alpha like? Thank you for doing that? And thinking that way, we need more humans who are systems thinkers. I think you're you're doing fantastic work with the. Thank you both for being on the show Dankali they really. Are for. People who are listening volume dot com, V. I o. m., e. NAVENE and I've teasing about this. He's still says Wyoming, but actually violent. So. Yeah, there, you go. And I just got to say yes I have a small financial interest because I'm an adviser, but seriously this is so cool. Have you been listening? It matters? It's awesome so please if it's within your means and your interest said you sign up for the test. Good on the I o.. M. E. DOT com. Use Code Dave except ten dollars and be one of the first people ever get this test. It is the single most impactful test I've ever seen. Bulletproof radio was created and is hosted by Dave Aspirin the executive producer Darcy. HIMES PODCAST Assistant Bev Hamson. PODCAST useful information only statements and views expressed on this podcast, not medical advice. This podcast including Dave asked the producers disclaim responsibility for any possible adverse effects from the use of information contained herein, Indians of guests are their own in this podcast is not endorser, accept responsibility for statements made by guest podcast, not make any representations warranties about guests, qualifications, or credibility individuals on this podcast may have a direct or indirect financial interest in product services referred to herein. 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Biohacking Alzheimers, Age Reversal, Young Blood, Stem Cells, Exosomes & More!

Ben Greenfield Fitness

1:39:32 hr | 2 years ago

Biohacking Alzheimers, Age Reversal, Young Blood, Stem Cells, Exosomes & More!

"Hey, it's been greenfield rated strap your propeller hat on because we are going to go for a deep scientific ride. This podcast is brought to you by what I consider to be one of the most versatile tools in my supplements cupboard, meaning I can take it at night before I go to sleep to enhance my neurotransmitter formation. I can take it before a fasted workout to increase my blood levels of some of the things that are super necessary for anabol- ISM, but that I don't get from some of the other common pre-workout foods. One might eat. And Furthermore, it's something I can consume and maintain all the benefits of being in a fasted state while still being able to charge very hard through workout without risking loss of muscle and without risking central nervous system fatigue. I have been using this stuff since two thousand thirteen iron. So almost. Six years. This has been a pretty potent weapon in my performance. My sleep and my recovery toolbox. It is called amino 's more specifically is called Kiana amino k. i. o. n. amino. It is a blend of essential amino acids, not branched chain amino acids which bike your blood sugar. Those little bastards. This is essential amino acids. Ninety nine percent utilized by your body compared with about forty eight percent for egged protein, even less thirty, two percent for meat and poultry and fish way protein soy protein eighteen percent only one percent of branched chain amino acids actually at utilized by your body, the stuff ninety nine percent gets utilized. You can grab it in a wonderful cool lime powdered flavor or in a tablet. I tend to just travel with a tablet need 'em like cookie, monster. I go through about ten to twenty grams of these per day. They're also really good for staving off your appetite too. When you're in a facet state, it's all over at key on their called Kiana Minos get k. i. o. n. just go to get kion dot com to grab those. Another thing that you may want to add to your toolbox. Should you be a fan of occasionally delving into pasta and bread and not wanting to go decommission a bathroom or experienced the somewhat embarrassing, bloating gas, and even more concerning gut inflammation and gut irritation that occurs from gluten. Now, I don't think Luton's the devil. Not one of those guys. I don't think that gluten is going to end their planet or cause World War three. But I do love to eat my wife's delicious, slow from it to sour dough bread that she makes like to take my kids to a local restaurant where we order these pop overs that are indeed made from wheat tonight. I'll take my family out to dinner and honestly, I'll probably have whatever bread they bring out to the table, and I will pop six of these. Before I actually eat, it's called gluten guardian. It's an it's a supplement has this enzyme called die. Petiot pep. Today's DiPoto pep today's, and this is a form of a protease that breaks down the exterior coating of gluten protein, and it makes it so that you are able to consume gluten with none of the side effects. So you can get it and you can get ten percent off of the already discounted price. If you just go to gluten guardian just like a towns gluten guardian dot com slash greenfield, I think that anything that helps you better handle Gooden is a pretty dang good idea. I didn't get the stuff that gluten guardian dot com slash greenfield. In this episode of the Ben refinish show, we hired a lot of nurses that were on this study and they saw recovery real recovery firsthand. So we're trying to get to a place where you know we can get more definitive certainty around cause and effect. Associate wellness done so we can all save time just as valuable to figure out what's not working. He's an expert in human performance Nutricia. Voted America's top personal trainer. One of the Globes, most influential people, health and fitness. His show provides you with everything. You need to optimize physical and mental performance. He is Ben greenfield power. Balance, whatever it is, redo the Thatchell. When almost studies done studies that the greatest efficacy. All the information you need. One voice right here right now on the Ben greenfield fitness podcast. Hey, this is a little bit uncommon that I would record the intro for you right now after that big commercial break that I realize you may or may not have fast forwarded through, don't fast forward through the commercials by the way I procure amazing discounts for you. I don't know if you're aware that a lot of the discounts I'm able to get for this podcast. I actually tell people, hey, can't advertise on my show unless you give my listeners discounts, they're not going to get other places. And so when you fast forward the commercials, you miss out on all that goodness. But anyways, that's not why I am recording for you right now before. I welcome. Fantastic guests. The show reason is we dove pretty deeply into the science on this show, and I want to of give you a summary of what we talk about so that you are armed in that your brain is prepped and should something go over your head. You're just kind of kind of ready for it. So the first guy that you hear talk on today show for quite some time. His name's Mark Armin. In all, introduce them in the show, but he has this thing called a young blood institute. There is enormous potential for young blood or what is called hetero chronic plasma exchange to actually reverse biological age. This is essentially the equivalent of putting the blood of young mice into old mice, except they're doing this with humans and even more amazing as you're going to find during this episode there actually reversing Alzheimer's with plasma replacement. So that's one of the things that you're gonna learn about. It's called hetero chronic plasma exchange, Mark geeks out quite a bit. But the long story short is that if you go to the young blood institute's website, you can see more about what they do. I'll put all the links to everything we talk about over Ben greenfield fitness dot com slash plasma, my other guests, Tom and Goglia because this is three way on this show. Tom talks next about aging markers and a whole bunch of different ways to. Track and test aging that go far above and beyond what I've talked about before. Like you've probably heard me talk about, tell him you're testing before and blood testing, but he talks about whole bunch of other tests and even mentioned this aging clocks booth that, frankly, the time. This podcast might be a little late for you, but they have this thing in San Diego called revolution against aging and death, RAD fest, conference whole bunch of scientists and doctors. They're primarily in the anti-ageing and what they call the radical on Javadi sector. They're going to be doing a lot of these ageing tests that Tom talks about there, but you can also just go to Tom's nicotinamide Atta anti-nuclear tied. It's a mouthful NASD clinically site and he'll more formation about that stuff. They're too speaking of AD. We talk about whether nicotinamide right beside which is the darling of the anti-ageing sector right now is indeed the only way to boost AD turns out spoiler it's not these injection. I've actually do cause an idea to be able to cross the cell membrane. Then we talk about this thing called Bredesen's protocol, which breaks down Alzheimer's into six different types of Alzheimer's, inflammatory what's called Gleich, toxic aid traffic, toxic vascular, and traumatic, and how this protocol by Dell Bredesen's book by author of the same name kind of lays out a multi modal approach to be able to heal Alzheimer's. And we talk about some of the little bio hacks tools that can be used for Alzheimer's. You'll hear Tom, he does a pretty good job deemed dropping things that I try to correct him on because I know these are names that you mentioned that you might not be familiar with. Like you talks about a person named Naty Brady. She says, Naty Brady a few times purchase person wrote a book on a d. neurodegeneration we talk about excess OEMs as well, and I will link to all the different studies that Tom mentioned as we go into those specific categories. Boy, when it comes to excess homes, one of the big things he talks about is that excess OEMs that you can get in ja-. Elected into your body. They contain something that I haven't talked about on the show before called GD f eleven m. r. n. a. and GDF eleven is this very interesting substances on only do you get it when you do these para bios experiments, meaning when when you replace some of your plasma with young plasma or replacement plasma, but GDF eleven repairs DNA in stem cells. It is something that people are injecting now claiming their hearing and their smell and their site are all coming back. It's the same in all vertebrates. You can get it from animals. Very interesting molecule. So we talk about that one little bit and I'll put a bunch of studies on that and the show notes to over Ben greenfield fitness dot com slash plasma. And then we talk about ways that you can naturally increase your GDF eleven levels to particular supplements that we talk about very common, easy to find care Seton and also what are called Toko trion all's about one hundred and fifty milligrams of Toko trion all's per day or about. Five hundred to eight hundred milligrams of care. Seton per day might even be more effective than some of these more expensive anti-aging supplements that you find floating around there. So the show notes are quite robust. I have linked everything from excess home said, gee, Jeff, eleven to this book the end of Alzheimer's. Other Alzheimer's references DNA anti-aging clock websites that they have to be able to determine your your brain aging and your body aging. The young blood institute website. Everything is over at Ben greenfield fitness dot com slash plasma. Again, this is a little bit more scientific than even some of my previous episodes, but I think you're really going to dig this one. So let's go ahead and join up with Tom and Mark. You've no doubt heard of this by now that in an attempt to live longer time, there are some crazy anti-aging enthusiasts out there who are getting themselves injected with the blood of young humans via. L. process that goes by a whole bunch of different names, but there's one form of this called plasmapheresis plasma freezes. And my first guest on today's show is named marker doll. He's a technology entrepreneur from the silicone valley. He's got a bunch of patents. He's worked in big data and he began his career at IBM's medical instruments subsidiary that pioneered this process of plasma free says he went on to found something called the young blood institutes, which actually does this plasma exchange therapy to rejuvenate the body stem cells and restore the immune system and prevent the onset of a whole bunch of age related diseases. So we're going to talk about that just a bit with Mark today, but it gets even better because I have another guest on today's show, and he's been on the show before I had a podcast a couple years ago called the next big anti-aging draw. Doug everything you need to know about in a d and in that podcast, believe it or not. We talked to whole bunch about this stuff called on nicotinamide added nine dynamically tied or in a d and as you learn in that episode, I guess Tom got very sick when he was in Costa Rica and he was prescribed a bunch of antibiotics. He suffered. Some pretty adverse reactions was told he'd have problems, especially gut issues, things like that for the rest of his life. He developed a whole bunch of food allergies, insomnia, anxiety, muscle pain, chronic fatigue syndrome. We went into his whole backstory in that podcast episode that I'll I'll link to in the show notes for this episode which you can access over at Ben greenfield fitness dot com slash plasma. That's been greenfield fitness dot com slash plasma anyways, though through Tom's eight year battle. He got prescribe. A whole bunch of different pharmaceuticals and eventually turned to this stuff called any Di, wow, around up long story, short completely curing him and getting him off all these medications. He was on and off hung out with Tom, and he just like this. This, I would describe him as a ripped beast now. So he's definitely come a long ways. And we, we raised a Spartan race together down in Las Vegas, and he's definitely come a long way since using these NA d therapies. And he's actually a guy who I talked to who's way on the cutting edge of anti-aging and longevity. And that's why this podcast is about a lot more than just young blood and in a d we're going to talk about biohacking Alzheimer's, and we're gonna be talking about reversing biological aging, different biomarkers, you can track and test how to measure biological age, the biggest obstacles to age reversal, how you can get more involved in the anti-ageing community all whole lot more. And again, all link to everything. All the studies we talk about all the previous. Podcasts besides everything. If you just go to Ben greenfield fitness dot com slash plasma p. l. a. s. m. a. r. so it's going to jump in first of all, gentlemen, welcome to the show, expand great, severe Ben. And in a second voice that you heard that was Tom. So Tom, you, you had the idea to have both marketing you on at the same time. So tell me tell me what it is that we're talking about on today show. Well, I think we're gonna be talking about, you know, Mark and do a very good job talking about young blood or heteronomy plasma exchange. I, we also wanna talk about the different ways you can measure biological age, and that's becoming more important as new types of therapies develop and just sort of explosion of information out there about about all these different therapies that may may reverse age and so we need to, we need to find metrics that could could monitor where we're at, and and then we also want to talk about Alzheimer's. Alzheimer's seems to come up because it's, you know, the the number one risk factor for that is is is age. So, and then you know, I did want to like to sort of dust the conversation with all these other different ways that we can potentially reverse the age and. You know, just I think we're going to have a little debate about an. That's unavoidable. So, well, we got, we got a lot of talk about, but you know, I, I have to thing that intrigues me the most right now from everything that you just listed off is this idea of replacing your blood with with plasma, and I would love to hear from you Mark. Exactly what this whole young blood institute thing is in, and I do know I'd love for you to mention this as well. There's another company in San Francisco. I think they're called him Brosio that's doing some kind of a blood exchange. I'm curious what the young blood institute is and how it's different than than this other company and Brosio that's doing from what I understand young blood exchanges and how this whole plasma exchange treatment protocol works. So can you can you jump into how we can all inject young blood into ourselves and walk around looking like we're thirteen years old. Well, I don't know if we're going to get to thirteen, but but we could try, you know, the the young suit. First of all is a five. Oh one c. three, non profit. Okay. So we're, we've got a kind of humanitarian research mission to conduct a clinical trials in what we call hetero chronic, you know, big word for different ages header, chronic plasma exchange, basically removing the old plasma and replacing it with a young plasma or purified young chirp plasma components. So yeah, obviously a lot of people have been discussing the concept, you know for a long time. There's, you know, other people out there that are. Trying this in different forms of the Umbro folks as far as I know, and I could be wrong. I understood from one of their MD's and Florida. I met there what they're really doing our infusions. They're not necessarily not necessarily getting rid of the old stuff in infusions me that they're taking like blood from healthy young donors and infusing that in into other people. Yep. Well, yeah, plasma. And just for people, listening in when you say plasma is at the same things blood now, plasma is is the the kind of the straw colored liquid. That's, you know, it's ninety five percent water, but it's fifty percent of your kind of blood volume is plasma roughly, and that's what's carrying all of your red cells, white cells, platelets, Munich, Alaba, Len's protein in, you know, Sutter. Cetera throughout the bloodstream as well as all the side of kinds in signaling molecules and so forth. So there there are, you know, the the primary components of blood are plasma, red cells, white cells, and platelets. There's a lot of, you know, detailed below all that, but there was the primary components and from what I understand Kirkman from wrong plaza was like about half of our blood volume. It contains like the proteins and the fiber engines the antibodies and and basically all the good stuff that you would find in blood. Bingo. That's all right. You know when I, I mean, I actually, you mentioned this, I think in the beginning, but I, I actually started by career of all things with IBM biomedical systems who had a invented, what we call back then to blood cell processor. They waited for my time back in the sixties. There was an IBM engineer named Joe. George Jetson who had a son with leukemia. Jordan Johnson, like the jets got not Jetson Johnson j. d. yeah, but but easy to remember and he had a son would look at needed regular, you know, white blood cell exchange, her Luca phrase as we call it. And at the time they had a manual process to separate blood all the blood components, specific gravity. It's kind of like, you know, oil and vinegar oil and water, etc. And put blood on a shelf in, it'll stratified, but basically invented this machine to draw the blood out of one arm, spin it around in a in a centrifuge while it spinning around inside about special, a little plastic disposable that would allow him to essentially extract as things kind of layered up. Any particular component he wanted could be white cells, red cells, platelets, plasma. So the first application for the blood cell processor was looked freezes motivated by the fact that his son had leukemia, and he's trying to figure out how to kind of automate the process and donate blood once a week instead of whole blood every or donate a component of blood once a week as opposed to hold blood every two months. And so he got leave of absence from IBM the got a grant from the National Cancer Institute, and you know some time around sixty five sixty six. They basically created this machine. And then I b m who's got kind of a history of, you know, into what we call enterpreneurial ventures created a business unit out of it. They let people know IBM actually helped with a Harvard professor create the first heart lung machine back in the forties, and they've done interesting little side project, but basically decided create a business unit out of this this this concept basically. And that's the business I joined when I got out of school at UC Santa Barbara and kind of by accident. But I'd gone down for an interview with the computer guys and I got there and they, they told me there was a hiring freeze in there are no jobs, but there might be this opportunity in this little business unit call by medical systems. And so I joined it and kind of got my crash course in medicine, Hanmi Tabor's medical encyclopedia calling on. I literally at the head of open heart surgery because they used our products and open heart surgery like my second month on the job watching watching the whole thing. And but then within a year of me joining they, they sold the business unit and they redeployed us into the computer group which was where I intended to go the first place and it really wasn't until a few years back when I started reading about the, you know, the mice research exchanging young and old blood, and I thought, man, this would be released doing humans. You know what? Why are they spending so much time with lice and. So they with mice. Mean talking about the mouse research, some people might not even be familiar with this mouse research. What exactly is going on with that. Well, they, they're. There's a fancy term. They called a hint chronic pair bios, which in a nutshell, a hurt me here. Bios. Yeah, that's. That's that. That was the other word I was looking for that. That's basically the word I see thrown around more than this plasma freezes para bios. Yeah, yeah, it's look. Let me tell you what they're doing. They're slitting open the sides of two mice. They're stitching them together. And they're measuring the effects of. The complete exchange, the call it the systemic Milou basically, meaning it could be blind could be gods. That could be, you know, all sorts of stuff that's just kind of float around. But essentially it's like they're creating. Siamese twins out of mice that were, you know, it's like it's the opposite of of a separate Siamese twins. It's it's like creating Siamese twins and mice, and then measuring, they basically, you know, stick together and old mice and the young mice, mouse and you know, measure what happens to, they're not actually taking a blood out of the the old mouse. And in that young mouse, they're actually connecting the two mice together. Well, that the the first range of experiments sort of starting in two thousand five. We're just stitching the mice together. Now in the last couple of years, they've developed some devices that is sensually allow them to deplete blood out of one mice or the other, and then independently kind of injected. It's a very difficult problem mice. 'cause they're very small and you know, they're Baynes are incredibly tiny, and so it's it's not a very sophisticated process. Let me say that compared to humans in. I mean, we've been doing this in humans for fifty years. I mean, we there are little oh, yeah. Well, since the sixties. Yeah. I mean, there are millions of procedures of all sorts of what we call a Fracis every year primarily for autoimmune diseases, which is the, you know, the big indication if you will probably half of the treatments in the world today. Our plasma freezes and and the majority of those are used for autoimmune disorders. Things like multiple sclerosis, mice grabs. There's a whole list of kind of a dozen a more rare diseases where they've found on what we call therapeutic plasma exchange. Has a beneficial effect in a removing profile. I'm a Troy factors ridding the body of an auto antibodies antibodies attack themselves, regulating tesol disorders of things like that. So, and that's where we made the connection. You know, I realize very quickly that I mean, I went to visit I, I've met a lot of the mice research people let me say that and, and they're all good people. But most of them don't have a lot of experience with human medicine. So when I set up the blood is a toot, you know, I did. So with an eye to recruiting, you know, the best immunologists Indian hollowest, nurse practitioners, MD's, etc. That have got, you know, real experience in real medicine and and in particular with plasma change. So you know, like most of our nurses have been doing this for like thirty forty years. I mean, typically, and so we've got, you know, institutionally a lot of experience with that and because I realized that you know what we've really got to do is explore these new indications that are, you know, plausible because we've done is sort of connect the dots between auto immune disorders or unim- unity and immuno senescence, which is essentially the the Munich. Well, turns out that autoimmune disorders and immuno senescence have three fundamental things in common, the presence of auto antibodies, the presence of of tesol disorders in the presence of pro inflammatory conditions. So the interesting possibility is the use of essentially an old technology to a new indication, which is, you know, aging disorders that are caused systemically by immuno senescence. Okay. So basically when you're putting the plasma from a healthy young donor into somebody who comes in there to the young blood institute, primarily what you're going after is a stronger immune system. Yeah, that was our original in remains kind of the bait. A school or hypothesis is that you know, we could reboot immune system just like rebuilding your computer right that that the majority of subjects are going to be on a path of immune system. Cl- I mean, we basically dive in unison essence right immune system craters and minute the craters it we become vulnerable to all sorts of different age associated disorders. Okay. So so what exactly happens when somebody comes in there. Well, first of all, what we do is we partner with guys like Tom, right? So Tom has a clinic in San Diego. Yeah, the injection clinic, right. And so we have a network of really doctors clinics across the country. And we partner with those clinics to host the trial and sort of provide the the oversight, the possibilities, the local MD, etc. We provide. We run the the what's called an internal review board. I r b study protocol. We provide the nurses, the protocol, the equipment because it's very specialized, and then we deploy into each location and we kinda share the responsibility there, qualifying the subjects overseeing the procedure generally, and then we're providing the actual. We come in kind of turnkey, provide the the plasma freezes service for the subjects in that location, and he's location. Are there any kind of risks to this? Like like if I was going to go down and do something like this because I want to track my telomeres and see what happens to those or if I want to get a stronger immune system. I mean, I is this the type of thing that just anybody can wander in and do millions of procedures are done a year. Okay. And in we have started with what is arguably the safest protocol. You know, possible where we use purified plasma components because you know, plasma is ninety five percent water. So there's a whole multibillion dollar industry that basically collects plasma donations. Usually they have plasma collection centers around universities in places like that. They then distill out the water. They take the key ingredients which are primarily the the albumin immunoglobulins and by Brennan and a pasteurize it which means heated up a, you know, wash it, purify it, and it goes through. You know, decades, old FDA regulated process, and it's kind of like, you know, frozen lemonade. I mean, you know the ship around the country, you know, add water got got plasma. So it's a very safe protocol. There's about a four percent risk of a transfusion reaction in the transfusion risk is roughly minor. It's not really that much different than if you went and donated blood at a blood Bank. Potential for flushing or fainting or or things like that, which usually after someone goes to the process, you just make sure they sit down for a little while and you'd have water, maybe a snack or something like that, but it's not. It's considered to be a very, very safe procedure. It's probably one of the safer procedures in the medical world today somebody comes in and does it do do get multiple plasma exchanges or you just do one plasma exchange, and I'd say you're done well in our protocol or at least our first protocol, you go through six exchanges and which is different than let's say, an infusion protocol in in the reason being that we're using specialized equipment to remove the old plaza and the the. But the fact is if you're drawing you're drawing blood out of one arm, you're spinning it around your extracting the old plasma. You're putting the other blood components back in the other arm, and then you're adding the new plasma while after after a while pretty soon you're drawing the old plus the new. It's kind of like trying to change the oil in your car while it's running and you didn't drain the oil pan and and so you can only get two thirds of the old stuff out. You too, roughly you plus or minus five percent, but before you know, I mean, that's kind of a max, and so you've got to wait let it settle a comeback within, you know, a week or so, and then do it again and there's a a curb. It's on our website, but there's sort of some mathematical siskel a history from the twelfth edition of hematology that basically demonstrates mathematically that it really takes six treatments to get rid of, let's say, ninety eight percent of the old stuff that's is that six days in a row, you're coming in six consecutive days or do you split those up six weeks in a row now? Six weeks in a row. Okay. Gotcha. Gotcha. So people do people need to travel to so Convalle in the young blood institute this or or like you mentioned your parting with clinics where people could go do this at a clinic in their town? Yeah, that's why we're doing it because if. If you live in San Diego, okay. Go to Tom, you know, if you live in Ralph Raleigh, North Carolina? Well, we've got a doctor there. You know, if you live in Florida, we've got doc, slayer. I mean, we've got doctors in Texas, you know, we I, it's it's and because of our model, it's relatively easy for us to add a new location. So if if we have somebody who lives in, hey, Spokane, Washington, and they want to undergo treatment. Kind of first question as well who's your who's your day? You know. You know, and you know, would they be interested in hosting the procedure and becoming what we call a sub principal investigator because they're actually a part of the study, right? We don't just, you know, rent space from these guys were we integrate them because they have a lot of wisdom and they're kind of like a human biomarker right? That that we identify all the data. From a study standpoint, but a doctor can make a enders frankly can make observations that get recorded into, you know, the the record for the treatment. So maybe they noticed that somebody after three treatments is hop skipping and jumping or dancing, you know, well, there's a, there's a, there's a relevant fact that we wouldn't capture it a blood test. Okay. So when when people are looking for place to go do this kid and they just go to the young blood institute website into a search for practitioners or where to do this in their local community, we don't really the list of practitioners on the website, but they can submit inquiry and we can work with them. I mean, we're the bottom line is we're flexible if we have a doctor in the area, great. If we've done and they've got a doctor, will that works to? Okay, I got you. So when people are doing this, what exactly are you measuring? I mean, what? What. What? What is it that you're looking at to see if this plasma exchanges actually working like I tracking biomarkers or or tracking specific data points. Yeah, I think that's probably the most significant thing we're doing actually, to be honest, because we've probably got lore technology testing capability than, you know, Stanford, John Hopkins, Harvard combined. I mean, we have sort of gone to the Matt with respect to a rolling out the most advanced sophisticated scientific test technology on the planet. Like what? Well, the the key technologies that we're using is called time of flight mass atomic Trie, which provides a extremely comprehensive understanding of self e-e-e-e-no type signaling pathways. It really enables what's considered to be a system cell biology at a a single cell resolution. It's called single cell protein, onyx, the large scale study of of proteins basically, and it's a very advanced. Method to to measure peanut type cells that can generate significant detail standing about the cells in relatively small samples, and it's sort of a successor to what's called flow. Tom, a tree over the last thirty years where we've been measuring immune immune systems and knowledge and so forth. So we've got literally semi to buy markers just on that alone. Then we've got some Elisa technology enzyme-linked absorbs now say it's it's been around for a long time, and we do a few tests using the old Elisa technologies because we can't get it on the new license. But then there's a new technology called digital license. Elisa Elisa e. l. i. s. a. n. k. stands for enzyme linked immuno absorption saying, and it's the digital Leisa is anywhere from one hundred to three, five hundred times more sensitive than the traditional LIZA. And that enables. Detection quantification of biomarkers that previously were almost impossible to measurement measure and and it gives us also automated results. So we can minimize operator variation and give us, you know, very sensitive, accurate detection of of side of kinds proteins, all sorts of assets. We've got about twenty four by markets. There. Then we've got a mass spec of mass spectrometry essay for Alzheimer's. That's novel in unique. One of our investigators is basically the inventor of possessing, and it's been. It was clinically proven in Japan. Back in two twenty, twelve twenty thirteen to be inaccurate measurement or roughly equivalent of a pet scan in detecting what's called amyloid beta plaque in the brain, but detecting the which is considered to be the least the evidence, if not the cause of Alzheimer's using only a blood sample. So problem with Alzheimer's is that typically went by the time you get diagnosed, it's too late. You get diagnosed goes, people are observing problems. You may not remember those problems you get in, you know, to get the diagnosis and the these diseases already taken its grip. And so that's the the big challenge because it's not necessarily obvious until it's too late. So what we're trying to develop is essentially with all of these things actually not just the Alzheimer's, but. Essentially, a series of early detection biomarkers that would allow us or enable us to prevent the onset of of a new number diseases before they actually begin to occur or be begin to become significant. So along the lines of, you know, Colin cancer breast cancer, early detection regiments that have been very successful. We're also trying to essentially develop a kind of a next generation of early detection techniques revolving around, you know, the immune system neuro immunology, the neurological disorders, etc. In. And of course, we also have incorporated DNA methylation markers and genetic markers in other had a newer more nascent types of quote, unquote, biological aging. The differences were not. Using those as kind of the key measurement. We're actually working with the meth laser companies to look at all of the the detailed sub data underneath so that we can correlate it with the other data that we're we're collecting. And so one of the things we're doing is getting a significant variety of different types of my markers and biomarker testing technologies that we can then correlate to get kind of the whole the whole elephant, if you will. Right, like anyone test or anyone approach, you know, you might be looking at the trunk of the elephant. He might be looking at the tail. You might be looking at the at the leg. We're trying to get the whole picture. And so nor do that we're getting as many tests as we possibly can, including a new one. We just we added a relatively recently. I mean, just just after we got started, but we didn't discover it until then, but we've got a new one on blood viscosity. Which turns out to be kind of interesting. But it turns out that you know as blood ages, it thickens. So there's been a lot of historical measurement of this in, let's say, research settings, but it really hasn't been translated applied to the buck the broad populace. And yet it kind of makes sense that if your blood is turned to sludge, it's kinda hard for your heart to push it around. So in what we've noticed in some are treated therapies is that when you're getting rid of the old stuff, some of which may look a little thicker than you know, in a young person. That after a few treatments, it starts to thin out or normalize, and we've had people report, you know, wow, I had the best sleep I've ever had my life, you know? And after getting a plasma exchange after getting, yeah, one or two positive changes. And if you look at the output plasma, in those cases in this is, you know, different people have different kind of experiences. Let me say that and we haven't because we cry freeze the blood in we are going to, we measured all at a future point time all at the same time, we don't have all our our our data and yet, but just experiencing what we're kind of seeing observing is that there are different types of blood, or let's say characteristics of of plasma that are coming out of people and those attributes are normalizing after you know, several exchanges. Hey, I want to interrupt today's show to tell you about, let me go. She paced omega both she placed. I actually just got back from Japan and this this stuff is called pickled Plum puree Leumi bushy, paste it is made from you guessed pickled parade only bushy plums and it replaces a butter and salt to allow you to make the best corn on the cob on the face of the planet. If you're corn on the cob guy, gotta get the stuff to put on corn on the cob. But it also works very, very similar to me. So which is something that I cooked with quite a bit when I was in Japan. Recently, it is a traditional Japanese product, but it's very difficult to find organic. Only both. He played paste and I don't even know if I'm pronouncing that one hundred percent, correct. If you Japanese trying to jump through the podcast and strangle me my apologies. For example, the ingredients in this particular roomy Bo. She's just we both. She plums cease old and what are called beefsteak leaves or Sheesh. So another popular Japanese ingredient while the finest organic stuff. 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I mean, if somebody can't get into young blood institute because you're tracking a lot of different things there, what would you say would be the lowest hanging fruit for people to actually track they just wanted to kind of do this on their own or talk to their doctor about running certain tests, or you know, doing like telomere length analysis through something like teloyears or something along those lines, what would be the best anti-aging biomarkers in your opinion to track. Well, that's a pretty tough question because to be honest with you, we're probably less concerned about quote unquote. Age as a as a human construct of the Roman calendar. Then I mean ourselves don't know about age, right? Our cells don't know that they're twenty four forty eight or you know, ninety four. So we're really focused more on is. The function of of of the body. And I will say, just on the telomere point the, you know, we are cry, freezing the blood, and we hope to be able to test future point on telomeres. But the problem with current telomere testing is that they typically excess telling her links on the total will be call a purple blood cell nuclear cell populations. PBS's derived from whole blood in basically PBS's have a mixture of cell subpopulations that have dramatically different telomere links. So like nave cells versus effector t. cells for example, or key cells versus in k. cells and t cells can have the longest teller links. So you could come in in the morning. We could do a blood draw and you might have a three percent total t. cells. And you know things look pretty good. And later that day we do a blood draw and we only get five percent T-cells, and you have aged ten years. So the the whole methodology around Tomer testing is sort of fraught with complication in. We're looking at methods of possibly spinning down the cell population subsets so that we could look at the differences in those specific cell populations. Subsets, for example, name CD four cells, CD T-cells, etc. That we compare apples to apples in even. So we're still not sure. I mean the national Beijing's done a lot of study on this. You know, it's it's not clear. There's an absolute correlation to quote unquote age so, but it is of interest in terms of its correlated value to us. So in we're not really kind of in the biohacking community, you know, I mean, we work with people who are bikers obviously, you know, in the sense of dialogue, collaboration, discourses, cetera. But we're kind of trying to get to the bottom line what, what what's working, what's not. And the answer is, we don't know. I mean, there's there's a line out there and just, you know, understanding which tests matter is a hope. You know import part of the equation, but you're, you're going to get your, you know, whatever tests you do. There's always going to be someone that's gonna poop who it because. There's so many different theories of of aging and and there's there's a few scientists that like the pooh-poohed the telomere length. And so it's just so that. So really the approach is to is to find multiple ways to. Measure, measure aging, aging markers, biological aging clocks, what's what's a biological Asian clock. So a biological agent clock if you want to, if you want to study aging, you're using various therapies. You might have to wait fifty years to see what the results are or you could do your study seventy five eighty five year olds. And then you know has something that's, you know, a certain statistical power in order to. Yeah, you won't have to wait as long or you have, you know. You know something like telomere length, it spits out a a particular age. And that would that that would be a another means to determine whether or not the therapies and he good. So the telomere length is one and then Zeino put out this DNA methylation. Aging tests. They have. They have a few now what's time. Oh, so Sino Simoes a laboratory. And they've worked with a scientist, Stephen Horvath who he's he's sort of bio statistician that hit that they looked at the, he's looked at DNA and he's he seen seen a pattern statistically from from methyl groups that are attached to certain parts of the genome. So at various points in your life, certain certain molecules attach and detach to the genome and based upon that, it spits out a very high correlation age. And so out of this decide correlation, there's even sort of they're starting to think that perhaps some of aging is coming from. Way in which the methyl groups attached to the DNA. Okay. So all right. Gotcha. So so as far as biological aging clock and how to how to reverse it or how to slow it down or are there any other things that you found? Tom, as far as ways you can track biological aging or slow the rate of this biological aging clock, you know, I don't have access to some of the some of the machines that that Mark does unless we partner together and we've, we've been kind. We've been, we've been talking quite a bit since we met at this cocktail party in Florida where he presented this. And we said, yes, definitely worked together because we're so passionate about aging and just the commonalities with Alzheimer's. What we've done in our nonprofit and at a treatment center is we've looked at some of the more popular inflammatory markers and we, we've also looked at. We've looked at. Part age, which is measuring arterial stiffness brain age, which is we use seen as vital signs to compute a brain age, and then long age. We're using sporadic tree, so how much you can how much air you could breathe out. And then we use Qatami tree to to detect the age of the skin elasticity. So those are some of the things that that that will be doing. And then also. We're going to be using. There's a new. There's a new instrument out market called age meter. That will be we'll have at RAD fest, which is a conference. This can be held in San Diego, September, twentieth so we're gonna have we're gonna have like we're gonna have one of the largest booths if not the largest booth Brad fest in Julene ivy's of NASD and Xs zome Mohme's and also we want to win this red festive temper. Twentieth September twentieth. That is hope you can get the podcast out. I think this podcast comes out like the week that that you'd be doing this RAD fast. So so tell me more about red fest and tell me more about this this, this anti-aging booth. So Mark is going to be there, and so he'll be able to talk more about. Plasma freezes, and also, you know, we will. We will be doing well, we wanna do is we want to really encourage people to get their their, their aging clocks done, and we're using a system called physio age that calculates the aging clocks and it'll spit out. An age, and you know, at the end of the day, it's the more data you can get the better they're, they're always, there's always not going to be enough data to calculate age and an aging markers. But I've really loved to have maybe, you know if legally possible have sort of a contest where people can sign up and and calculate their age, and then maybe the next RAD fest we could figure out who's who's who's made the most progress or or whatnot. And yeah, so RAD fast is is something that I'm very excited about. I think that this is a, it's an amazing conference. It's very different than than some of the other conferences what is read I and for. So so RAD fast is the revolution against aging and death. It's the biggest conference on on radical long jetty, and it's it's a place where you can go and and and hear about studies that people are doing. Trials, make investments have dinners with scientists and doctors. And use this. It's a social gathering and it's it's a nonprofit. So it's pretty printing expensive. It's just a few hundred bucks to go and get a ticket there. And and I think Mark and I will be we'll have a side room to talking about maybe doing some other case studies. I know Mark and I are very interested in and looking at other ways besides this very promising, a plasma freezes. So I, I mean, for example, I had lunch with with the scientists two months ago, Greg Fahey we were talking about. He wanted to talk to me about an NA detests that he was working on. And he said, he's, he said, this is a huge game changer. So he he wanted to. Maybe have some sort of partnership and figure out how we can help each other. But he's but this little do. I know I find out later that he's, he's like, he's that he's developing therapy for thymus regeneration. And because if you if you lose your immuno senescence and you know you could be healthy like Jack Elaine and then catch pneumonia and a few days later you're you're dead. So that's one of the things he's working on. And he's one of the foremost authorities on crayon IX or chronic vitrification, which is is taking cells or organs and and chronically preserving them though. So it's so I had no idea that who I'm talking to and and then you know, these are. These are people that I've met at RAD fest the last couple of years, and it's it's a great environment to. See people that are very passionate about longevity. You guys are obviously you're talking about things that I have not heard anybody before. Talk about when it comes to to aging longevity. But one thing just just just to clarify here, what are the different parameters you're measuring at this booth? Just just list them off again because it was very interesting. You talk about long skin. What are some of the other parameters here. So. Hard age or arterial stiffness. And then I think it's called the stigma core and brain aging. We're gonna use the gold standard CNS vital signs and then you've, you've done those those air tests. I, you know. Sporadic tree where you blow as much era out of your lungs as you possibly can. And then then there's a skin test that uses a laser to measure the scene elasticity of of your forearm and produces a skin age, and so you've you. So looking at all these different parts of the body, you're, you're able to get a better handle on what it is your age ages. And you know, of course, DNA methylation telomere age or they're, they're, they're even better when they're all when everything's measured together and and we've got it. We got a couple of other ideas for for aging clocks as well, and I'm going to be speaking there. So I'll speak a little bit more about the agent clocks that were doing encouraging people to to get involved and to see if we can make changes in in life expectancy because. Our life expectancies dropped three years. They'll be three years in a row, so and our health span is is declining as well. So this is something that I get really excited about. Interesting. You guys are gonna be measuring a lot of things, so so RAD fest, I will all link to that in the in the show notes over a Ben Greenville finished dot com slash plasma kind of last minute, but folks want to want to get over to that and check it out. It's in San Diego, right since San Diego yet. Okay. All right. Gotcha. So that I mean, one of the things that I talk with you the last time that I had on the show about Tom was this concept of NA d. m. talked a lot about NA d. but one kind of elephant in the room that I wanna make sure I address while I have you on the show is this idea that was mentioned by Dr Charles Brunner. The last time I had him on the show and we were talking about nicotinamide riboside or an are, you know he has a supplement called a true Nigen or chrome IDEX, you know, Thorne has one. One Alesia m- basis is another one. A lot of these folks are saying that compared to any d- that Anwar is far more absorbable and a much better way to boost your energy levels. And we know that the NASD to NA d h ratios are really important as a way to control aging into enhance, might O'Connell health and overall health in general. And I personally, I take Antar, but I do these NASD injections. I've been down your clinic and have done in the IV I do right now on a weekly basis. I do an AD push Ivy self administered. It's I, it's one of those things that's controversial though, because a lot of people including Dr Brenner will say that NASD can't enter the cell membrane like an are supposedly can. What are your thoughts on that? Well, how do you feel when you inject NASD versus taking are while I feel absolutely amazing. But I'm wondering if part of it is because the injection process sucks so much and you get so like nauseous and your gut feels like it's on fire. I, I wonder partially whether or not some of us do to just the extreme relief that the actual injection is over. So I feel like a million bucks, but you know, subjectively, you know, all joking aside, I feel amazing when I do my NADA injections and I can't say feel the same immediate noticeable effect. Y take anarchy. But again, there's a lot of confounding variables right again a needle in my arm. I'm getting this stuff injected. You kind of have that rush of adrenaline just from the the injection itself. So I mean, I'm more interested in data than my own subjective feelings. I, you know, I have to do the fast injection. I, I'm not sure if I want to. It's on congress. Able to do it. Yeah. I mean, that's that's like being run over by a steam roller or something like that. Yeah, I have. I have to like box breeding the whole time takes him about fifteen to twenty minutes to push it all in. And I take out like a trash cans so I can pew if I need to from the nausea, and but then it's over and I saved myself like you know, six hours in a flight to San Diego baby. Okay. All right. Fair enough. Well, you know, you know, many NASD scientists. Any scientists usually say that d does not cross the plasma membrane so that that the sort of consensus is is sort of there. And I personally disagreed with that. There was there was a you. You were just you just sent me an article, but I haven't had a chance to read it, but there's also there was also a journal Brazil any. There's an Italian group in two thousand one that showed that an cross can cross the plasma membrane at the three t three fiber blasts, which are mouse embryonic fiberglass. So they used something called proteome. Light was homes, and they figured out that any crosses the plasma membrane, the the humidor Muslim protein called connection. Forty three. So if you disagree with that. Then one could always go onto sigma all just website and by three t three. Fiberglass for four hundred dollars and they'll be shipped to your door and you can run the experiment. But you know, I, I really liked the research that was done. At the conference that I held last January where. We're Ross grant who you interviewed talked about the uptake at any d. I'm not sure if win that'll ever get published, but Naty Brady showed. An increase in part bacteriology and cert one and certain micro Arnie expression. And so you know, I thought that and some of his, some of that research is sort of trick trickling out. And you know what, what what I'd love to do is. I was just talking with an enema in. It's in a modern mono, nuclear tides scientists and he he wanted. He's he's also a an MRI expert. He's been doing he, he's trying to sell some. I think he was selling some technology, the government to detect lies with his MRI, but he he wants to use the MRI much like a Hubble telescope goes out and peers out into the into the stars. He wants to use this me-right appear into the brain before and after an day treatment and actually count the molecules of NA in the brain, which would be. So the hypothesis is that not only is in in the brain, but it's also a crossing the cell membrane. So so he asked me to sponsor that, and he wants to look at that for an amended AD and I said, shirt, let's let's let's give it a go. So, yeah, so I, you know, there's, there's a, there's a, there's a bit more information and we'll just show that in the show notes, but it's it's kind of neat to see the controversy in debate, but I really do feel like. To really debate too extreme, I think, is really unhealthy. You know, I think that you know the the FDA the FDA thinks that we wanted that we should decide what which is the safest and best vitamin b. three therapy, whether it's an n. or are or niacin, or what have you. And and they're using their misinterpreting the law called the drug quality and security act, which goes far beyond an there's four hundred fifty, three ingredients that the FDA the FDA is pharmacy compounding advisory committee. Is that they reviewed and that they've refused to review three hundred ninety ingredients and and peacock has further rejected seventy one percent of the forty nine ingredients that they've reviewed sedate. So despite a long history of safe use and patient needs. So there's it's. What you have is a number of things that you love Ben. Okay. And that a lot of our listeners love. Are being threatened to be taken off the market, and it's it's pretty sad. Being threatened. It'd be taken off the market. They just they like incr- compounds like glued Afyon, for example. It's that that, for example, of glutathione push that's being threatened right now, it's going to be. There's there's a review. They're sort of. It's almost like a court hearing, and people are going to argue for and against glued defiant and it usually about two or three weeks. Vs or junctions of just like in general. Glued Afyon general. So that means glued to take it off the market for compound pharmacies. Yeah, this means veterinarians opthamologist. All I mean, the general public though that and I'm not that many folks are using glutathione in that form, right? The compound form. Well, I mean, if you go to a functional doctor, I mean, that's a pretty common. That's a pretty common IV of and it doesn't end there. I mean, there's in most people are just ordering all Amazon. You like liposuction defy on whatever. But the take is not that, you know, it's not necessarily that good people have digestive problems. You know, there's other things too, like firemen, curcumin selenium, resveratrol, magnesium glycemic eight vitamin a zinc Colin eight. All those all those vitamins. I just mentioned are vitamins that we use in. That we wanna be using our in Alzheimer study that we're doing is we're, we're combining Bredesen's protocol Bredesen's protocol with I n d. We'll be doing a lot of that stuff orally, but I need it. Just those vitamins that who knows. I mean, there's a lot of Parkinson's patients that rely on blue defy on. There's there's vegan that want metal be twelve and there's a real risk that could go away. I don't understand why. Why would it go away? Why would they want to do that? Well. I, I have my own reasons, but the the reasons that they stayed is that you know. You know, safety is a concern, but the reality is that you can't. There's no money involved in proving the safety of these, these, these vitamins that don't really have any intellectual property. And so if there was then essentially, as soon as soon as that that occurred, then the price of these vitamins would go up and so health care costs go up. But basically you not only do you have it's sort of threatening to Natura pass and functional medicine doctors, but it's also threatening to the cost of healthcare itself. So this is sort of what's going on. So I don't necessarily want to. I don't think that a debate about an and is necessarily is necessarily a healthy one. I just had there's a there was a girl the other day that called up the center. And she said. She said, I'm hallucinating and, and I said why? She said, well, I took levek win and I have massive anxiety and I'm loosening, like we'll hang up and down. I went one and go to the. She's like, I just came from the yard. They, they just kicked me out and and I was googling around and I found you and you know, what should I do? And and. I was like, I'm not a doctor, so you know, but there's a based on some information I got from Dr Todd, the pine he he's, he's a prescribing six hundred milligrams of c. which converts the glutathione and magnesium, you know, four hundred milligrams or Graham. He's able to stave off some of the problems of adverse reactions to to to fluoroquinolone antibiotics. And so you know, lo and behold, she goes out and she, she, she does. She takes that. I told her to go see a doctor, of course, but she, we were communicating and she said, know now the hallucinations are as bad as they as they were. They've really, they've really calmed down. My anxiety might Sonya. And so you know, doctors need to. There really should be some freedoms that doctors and compounding pharmacies and patients have when when when they're really desperate and they don't have anywhere to turn to. You know the silver, for example, silver IV's is alternative to these these antibiotics, and that's being threatened to come off the market. The Moore the from from, you know, the three wise men. I mean they've taken for, they really want it if the wants to go after merger would emerge you. So, I mean, it's really just the sort of threat to all the other potential sort of NASD therapies out there, the making and to healthcare costs. And so that's that's really, and I really think the FDA's really the biggest obstacle to to longevity. That's what I wrote. So. Okay. Well, I want I want to get into Alzheimer's second, because I know you've been looking at that quite a bit in both. You guys have some some, some pretty big thoughts on a multi modal approach to Alzheimer's and we can do about Alzheimer's. What before that you had briefly mentioned article that I sent to you, Tom about an uptake and this this one I will link to in the show notes over Ben greenfield finished dot com slash plasma, but it does show that most. Mammalian cell types can transport in a d across what's called the plasma membrane from the extra cellular medium and into the cell and it. It does actually show a pretty significant amount of NASD uptake despite the people that sell the NRA supplements, which I have nothing against those ourselves at work, but but a lot of folks will tell you in d. can't get absorbed and I just over and over again. I see data like this and like you've just alluded to Tom, the shows that it does so so that that whole debate, I think we, we could probably put a nail in that coffin and say that NA NASD does actually get absorbed, you know, and and and again, for those you want to look at the research, we'll put some over. Ben grew to Venice dot com slash plasma, but I know you have been using any d to fight Alzheimer's disease on. I know you guys have been using something called the Bredesen's protocol. So tell me about what you've been doing when it comes to Alzheimer's? Well, you know, I I've heard about Bredesen's protocol and and when I've talked to a lot of functional medicine doctors. They just light up when they talk about Dale Bredesen's and what he's what, what he's been up to with Alzheimer's and and there was a speaker at my conference. He talked about how he was combining with. With with with with Bredesen's protocol and he was seeing, you know, very good anecdotal results. And by the way, Ben, we'll be selling those videos with the discount and we'll put those in the show notes as well. So if you've watched if you're listening to this podcast that you want to watch the videos, and then we'll also just bundle that with the next n. conference that we're going to putting on February two, if you want to go to that as well. So, but but you know, Alzheimer's is a five hundred billion dollar disease. It's the six leading cause of death, and it's part of that five percent of society that that makes up fifty percent of the cost of healthcare and. So we, we, we think that, you know, you know, looking at everything that we can to to reverse Alzheimer's is a is, you know the the risks outweighed by, you know, the potential of looking at a lot of different therapies. And so I've and you know, when you look at some of the things that Bredesen's does, you know? So Bredesen's protocol. I mean, he he talks about using a metaphor where Alzheimer's disease is like a roof with thirty six holes. In which you know if it's raining, you're going to have thirty six leaks and each each each hole needs to be filled in order to achieve the best outcome and even reverse a, he claims even reverse Alzheimer's disease. So the thirty six hole roof represents thirty six, metabolic imbalances in the brain. And while previous Alzheimer's drugs are six, six successful at filling one or two holes. His protocol addresses all thirty six holes. So so he sort of breaks down Alzheimer's into different sort of sub types. So inflammatory. So inflammatory markers Gleich Otok seek, which happens to deal with. Sort of high carbohydrates or diabetic, and then there's a trophy that has to do with. Sort of hormone related, and then there's toxic which has to do with things like micro toxins and heavy metals, and then there's vascular Sakaria vascular, and then traumatic which has to do with brain injury. So you know, it's what's you know, people like the poo poo, like. Say it say it's sort of like. He seems to bring up a lot of the things that you bring up like Kito service and using m. c. t. oil and it just it just if it's well with me and you know, doing intermittent fasting. So he has sort of twelve hours off intermittent fasting, three hours eight, three hours before before going to bed. You know, doing low carb diet, this sort of thing. It's a lot of the stuff that you've talked about for a very long time. And so it's exciting to see sort of the cross pollination. You know of what you see in sort of biohacking world and and you know, sort of paleo world and what's what's happening here, and and we've been. So we've been looking at, you know, filing an eye are to do the NASD with his protocol. We actually even wanted to throw in the v light. So I, I stuck v light up my nose and what the v. light is. That's the photo bio modulate the basically like the laser light for your nose and for your head that they've done some interesting research behind Ivo podcast on it. But essentially it's a, it's like photo, bio modulation, like like infrared therapy that you put on your skull like a helmet. I have one sitting here beside me. It's right next to me right now. 'cause I wear it about every forty eight hours and it causes an activation motto. Qendra neural tissue causes a release of nine. Oxide to to pretty powerful little headset. Yeah. And and the manufacturers doing this study with Alzheimer's right now out in Toronto, we just think it would be when you're when you're going after Alzheimer's, you want to just throw everything that you can. If you know, it seems like we think we seem to think that it's rather safe therapy to combine. So. So you know there's a ton of precursors that that have been sort of. You know, there's been. There's been a lot of research that has been linked between NATO precursors and Alzheimer's, and you know, Bredesen's uses resveratrol and uses nicotinamide riboside. We'd like to, you know, because because anecdotally, what you see in with functional medicine practices, you see. Pronounce sort of cognitive changes with the issue. We think that we hypothesize that potentially using pure any day is going to be promising to reversing this, this nasty disease. So we talked to Naty Brady about it. He he wrote the book on a d. neurodegeneration and aging and he, he thought it was a great idea. So so so he's he, he's, he's asked to be your primary investigator and. And he's, he's, he's, he was the first scientist show that any d. levels decline with age. So you know, it's it's a pretty good pretty good win to have him on on board, but there's so much out there and that's what gets us. So excited that gets. That's what gets Mark Mark. Nine excited. I mean, like you know, maybe even the potential of using these exorcisms that you've been talking about for for guys using those as well, like homes and you would use them for Alzheimer's. There's a, there's a protocol. The the the era has for Alzheimer's. It's kind of music Kaya Mira is is the lab is one of the labs. It's producing sort of this undifferentiated broth of. Placenta derived. Exit zones. So gosh, that's a big big term. But basically I'm not. I'm not the best at explaining what exit are you're probably better maybe, but there. Extras, Elliott vesicles that they're sort of like sort of messages in a bottle that communicate between cells vesicles back back when I was taken exercise physiology chose these photos of. So these diagrams of cells. These little tiny circles getting released from them, and people just thought that they were there essentially, almost like junk that the cell was releasing, but it turns out their actual signaling molecules and have specialized functions like, you know, not just inter cellular signaling, but like waste management and blood coagulation, and they can also win combined with stem cells or even in the absence of stem cells. It appears actually allow for better trafficking of certain, you know, I guess like like nutrients signals, etcetera, from cell to cell, they essentially are like the. You know, they're, they, they're, they're like the the carriers, like the taxis from cell the cell. So they influenced the immune system in the immune response to pathogens and tumors in and again, you, you know what? I got injected with stem cells. They were almost used as a way to upgrade my stem cells. So yeah, pretty pretty fascinating what they all can do and they come from this lab this lab that you just referred to? Yeah. I mean, they, they take, they take stem cells and then they, they treat them in such a way that they they sh. They shed off these. These these Xs on these messages on the they might be proteins Arnaiz micro Arnaiz, and they're coming from this sort of ridge rejuvenate rejuvenate, Tori, sort of. Placenta and you know they've been, they've been using them for a number of different issues. I mean, you you and I know of a, we have a common friend who had spinal cord injury and he's, you should probably put that in the show notes. I had signed a release, but he, you know, he, he seemed significant improvements in his spinal cord injury where he's able to bend down more. And he's been able to lose as been able to have improvements in style and tone and specificity from from the spinal cord injury, and it's just gets it's those moments that that makes you want to. You know, go further and see how exciting sort of cutting edge science can do. But like the the cool thing is these, you know, these exits homes their homing capability, and they, you know, they could some are anti inflammatory immunomodulating and talking with the lead scientists. They're, you know, not only do their exams, have the, you know, the GD enough and beady enough. These are sort of neuronal Arnaiz, but it also has this sort of this GDF eleven micro Arna which is like sorta dislike. I dunno GDF eleven is is sort of. It's a, it's the RA. So it produces the protein. That you know has this has real potential. There's a I've talked to. That's the interesting thing about talking to people from Brad fast. You talk to some of some of these folks that there's this one lady that I spoke to, and she's claiming that her her biological aging clocks have gone from her seventies to or thirties, and so you know, Steve Perry, he's going to be speaking route fest. He's going to be speaking about these hundred individuals that have took it upon themselves to inject themselves with GDF eleven. But these eggs 'isms have the RA for GDF eleven. So it's like these sort of copy machine for GIF eleven. So you get this GPS eleven, which is like a DNA repair molecule that would act on on stem cells to make them active again and has like a little bit about GDF eleven. It's got some pretty potent cardiac and muscular and neural effects. But what you're saying is that excess OEMs would allow you to get the same. Effects as GDF eleven or enhancer GDF eleven availability put essentially. I mean, no one really knows. I mean, this is a lot of this stuff is is is so is so new, but what you know, I it no one really like I, at least I don't know what, what, what potentially could come out, but you hear you hear sort of these stories at least with the people that have, you know, I've heard more stories from the people that have you know, taken the GDF eleven. If they've seen improvements in in incident Jackson, you get, it's like a very, very, very small dose, and they seen improvements in sex drive and seen improvements in hearing and smell sight and things like, do you guys do that injection down there at the NFC Clinton. No, but we'd like to, I think there might be some some legal hurdles to go through in order to make that happen. So we'd be looking into that. You know, you'd have to find a way to procure it. And, but it's just a really exciting part of of of longevity right now is this GDF eleven? It's a hot topic that you know the bottom line while elba's biohacking gonna find in Colin interesting is Honey actually measure results, and in a lot of people got stories, but you know, we're the real fundamental question is where's the data? What data supports what result? And you know, that's kind of what we've been focused on is okay. We've kinda built a a platform to test in it. I think. I think so. I would say Tom or or ban. I mean, anything you guys come across you think is merit worthy. You know we're in. I mean, we'll test because you know, we're looking for a common yardstick to sort through, you know, the myths, the stories, the hearsay, and all that to get to hard data that says, hey, we saw these changes in the salary of cited kind panel, you know, or we saw the stem cell project or panel changed or or whatever, you know, and look all the how people feel. You know what they're kind of anecdotal sense of things is, you know, it's interesting at the most fundamental question is, are you detecting potential problem and preventing it? You know, are you rejuvenating something that you can measure a chain? Can you measure Maya? Genesis, you know. A growth in muscle cells, neurogenesis growth in brain cells as result of some treatment therapy in. And so that's that's kind of the most fundamental issue. I think in the anti-ageing world right now, it's a crazy cacophony of characters. And you know if we're all going to benefit from this it the other day, we need a common yardstick and or common yardsticks and Tom's got a lot of coal stuffing's add the mix and and you know, we're kind of test junkies. I mean, we'll take anything that seems merit worthy, but we'll be equally critical of of tests that aren't merit. Were they in right now? Telomeres you know, that's kind of on the list of having merit it it. It kind of feels good, but you know, could change day to day based on on the random blood draw. So we're trying to get to a place where you know we can get more definitive, sir. Certainty around cause and effect associate while the stuff so we can all save time. Let's, I mean it's just as valuable to figure out what's not working. One of the other things I wanted to ask you guys about to is this idea of Santa lyrics, because I think I think it was Tom, I talking about semiotics or the this idea of senescence cells. Can you guys get into central a little bit and how that works. Can I just say one more thing about Alzheimer's and then before we transition over there? Yeah, I just want to say that there's a study that's been going on or that concluded last year over the last four years using therapeutic plasma exchange to treat Alzheimer's patients it. It hasn't been published yet. There's been some interim results published in two thousand sixteen in there on her website. There's a link to him in the references section, but punchline is we hired a a lot of nurses that were on study. And they saw. Recovery, real recovery firsthand. And these are grown not like these are not like newbie nurses just out of nursing school. These are like nurse practitioners with thirty forty years of experience who can tell you actual stories of actual people who actually recovered as result of treatment therapies and their families. So we're probably going to have a whole separate branch or arm that we're gonna create. It's going to be more Alzheimer's or neurologic specific right now, we've got kind of the big net for anything and everything anti-aging, including the minimally invasive ultimate blood tests, but we're probably going to, you know, toward the this year beginning next year, create a protocol that more or less mimics the protocol that was used by Griffin over the last four years over hundreds of patients in thousands of treatments that, as I said, hasn't yet been published, but we have a pretty good word that worked and and we're pretty confident with the I've bet with some of the principal biscuit as well. So we're, we're pretty confident that you know when they do publish, you know, they'll show a positive results as result of the treatment therapy. And the cool thing is it's like, hey. You know, I think we're gonna find out and you know, I mean the the breast of stuff is great is a lot of folks working on on diet and neurological disorders and so forth, which we'd like to test by the way put under a real formal clinical trial, but it may be a combination of these things and it's like, I tell people, look, we can change your oil, but if you keep putting garbage in the tank, you know you're going to screw up the engine again. So you know, there may not be one right answer here, but the key is getting the data around this in in. We're going to have the most advanced most definitive mainly they give up blood tests in the world for Alzheimer's that you know will objectify. Yes. Some of the answers here. Wow, that's fascinating that you guys have gotten those kind of results with Alzheimer's. I've never heard of it being reversed to that extent that that's going to be very interesting for a lot of people. Well, it's these are right now. You have to put it in the category of, you know, nurses Lor because it hasn't been published, but it was a very rigorous clinical study and we do expect they will publish their results. You know, within the next six, twelve months. And you know, just sort of got a jump on it because we hired a few nurses that happen to be on duty administering the treatment. So what about this Celtics thing? So, you know, I mean, unlike plasma for recess that has so many years and and and it's been used. So many times send Olympics is sort of a newer is a newer technology. It's it is a broad term to describe a small molecules which selectively induce death of the majority of senescence cells. So senescence cell is they're basically like zombie cells that live in your body. And as you age, you accumulate more of these ambi- cells that don't really help out the rest of your body and they, they excrete. They excrete. The give off chronic inflammation, increased risk of cancer and and see creed pro inflammatory cytokines chemokines, and an extra cellular matrix proteases which contribute to aging and cancer. So there's companies like you need bio biotechnology out there, but I've spoken to some people, some of the the, the folks that are that are that are at there'd be at RAD fast about how they've been experimenting with some of these, some of these therapies and some of them. I don't even really wanna talk about because they're so new and there's sort of risk a parent to them, but but the idea is to get rid of some, but not all of these zombie sales because apparently need to have some some of these cells to keep a to keep healthy. You don't want to eliminate all of them. But I mean right now what you're going to what you know life extension had, they think did an article. And I'll post that in the notes where they're recommending taking one hundred fifty milligrams of Tokyo. Trine Alza. It's like a vitamin e. spectrum. Per day and in fifty or sorry, five hundred eight hundred milligrams of course. Quercetin per day as a. As a way of of of minimizing the damage from senescence cell. So it's really exciting because it's it's his anti-aging therapy that that that I've heard people talk. They've heard people talking about how they, they've got more energy and you know the, the remorse, an in-depth sort of more knowledgeable explanation at RAD fast. So so care sit tune would be a supplement that you would take to actually stave off the development of these senescence cells. Yeah, quercetin I, it's found in onions, and then. Apples to apples. Yeah, that's right. But you would take like supplement form to get a lot more than you get from, say, onions and apples. Yeah, I think so. Interesting while there. I mean a lot of this stuff, people are just unaware of what GDF eleven injections or even in a d. IV's along with, you know, the reverse of Alzheimer's from things like plasma exchange therapy, or in the use of these carrots tin and and took a trion all's to to decrease senescence cell formation. I mean, there's a lot here and I realized that we've only really scratched the surface. I know you sent me a ton of studies. I need to dig through and add to the show notes, Tom, and I'm gonna be doing all that and creating some pretty robust show notes for you guys who wanna take a deep dive over Ben, greenfield, Putin's dot com slash plasma. I know we kind of scienc- during today's show and my apologies. Hopefully everybody was able to kinda kind of keep up with some of the stuff we were chatting about, but I would recommend that for any of you who are interested in kind of keeping your finger on the pulse of all this that you. The check out the links alive in the show notes and you follow what Tom is doing and you follow what Mark is doing because I do talk to these guys and they really are on the cutting edge of a lot of this stuff. And I, I would recommend that you follow them, follow their clinics and again a link to everything also link for those. You want the last minute to get into this RAD fast selling to RAD fest in the show notes and props for those who like to plan things out and and planet your conferences in advance. Also linked to this NASD conference. That's gonna take place in February for who wanna get down to that. I'd all probably go to that one myself. I don't think I'm gonna make you to this RAD fest, but I'll probably be at that in a d conference and. Tom, Mark, anything else you guys want to bring up before? I let you go. Great job in expand. Awesome. Well, thanks for coming on guys. And and again, folks, if you take a deep dive and stuff, just go to Ben greenfield fitness dot com slash plasma. That's been greenfield fitness dot com slash plasma. I'll put links to all these conferences, all these studies pretty much everything that we talked about in the show notes over there and till next time on Ben, greenfield, along with Tom and globally a- and Mark Erdal signing out from Ben, greenfield, finis dot com. Have an amazing week. Bream this clause. Then greenfield fitness dot com for even more cutting edge, fitness, performance advice.

young blood institute Tom Alzheimer Ben greenfield Mark Armin San Diego scientist IBM Florida nicotinamide Harvard partner Japan Munich America Kiana Minos
How To Get Your Own Vitamin and NAD IV's, The Truth About Umbilical Stem Cells, Peptide Injections & Much More With Dr. Craig Koniver

Ben Greenfield Fitness

1:17:02 hr | 2 years ago

How To Get Your Own Vitamin and NAD IV's, The Truth About Umbilical Stem Cells, Peptide Injections & Much More With Dr. Craig Koniver

"Hey, what's up you like to stick needles in your arms? This podcast today is for you know, well, I'm actually not totally joking. All all at the podcast, guests explained. But I honestly think this is one of the better podcast episodes ever released in quite some time. I personally was on the edge of my my seat actually was sitting down. I was kind of on a stool thing. But I was on the edge of my standup stool thing. So anyways, I'll let you be enchanted by this guest the same way that I was his name is Dr Craig Conn Ivor today's show is brought to you by something that you may not be aware of. But that exists over. Well, tell you where it exists in just a moment, but it's got pretty much anything that could ever be used to heal ones. Joints or to allow one's muscles to recover more quickly. 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My sexy, Salteri radio announcer voice, seared chicken and Honey mustard sauce with roasted sweet potatoes. Chipotle black bean case Adidas with caramelized onions, and even zesty chickpea and kale. Saute with Zad Zeki and sunny side up these and many other fantastic recipes are able to be delivered to your house every week by this company called blue apron, and the cool thing about it is you don't have to know how to cook. But you can learn how to cook as these recipes get sent to you because they come with cards. They come with ingredients might children make them. My kids have actually learned a ton of cookery techniques using these fantastic blue apron meals that just arrive at your house even have different things going on for example. Like Bob's burgers inspired chef designed recipe and a whole thirty approved meal plan, and it's it's just super duper convenient and allows you to skip a lot of meal planning and shopping and just get straits to cooking. So what they're doing is gonna give everybody who's listening in right now chance to get your first three meals free. Not a chance to there's going to give you your first three meals free. You got to blue apron dot com slash Ben. That's blue apron dot com slash Ben to get your. First three meals for free. Blue apron better way to cook. I have a master's degree in physiology bio mechanics and human nutrition, I've spent the past two decades competing in some of the most masochistic events on the planet from seal fit cocoon of Spartan ago. Gee in the world's toughest mudder to thirteen ironman triathlons. Brutal bow hunts adventure races. Spearfishing plant foraging, free, diving bodybuilding and beyond. I combine this intense time in the trenches with a blend of ancestral, wisdom and modern science searched the globe for the world's top experts in performance, fat loss recovery, gut hormones, brain, beauty and Braun to deliver. You this podcast everything you need to know to live in adventurous joyful and fulfilling life, my name is Ben Greenville enjoy the ride. Hey, folks, it's Ben greed filled here. And I don't think it's any secret that for quite some time I've been doing a weekly admittedly, self administered. Although that's not necessarily advised a push I the Apure shy the with this potent cocktail vitamins in Gouda thion, and I've also talked about how I actually have been doing a weekly N A D, I V as well. That's that really powerful anti-aging molecule have discussed below before on the show. But it's something that I inject. And while you may not be quite willing to hunt down vein in your arm at administer your own issue. Which again, I do not recommend the doctor who actually get these ivy's from and who also has people fly in from all over the globe to see him who also. Trains practitioners in this whole idea of how to implement this style of what he calls performance medicine into his practice. Well, he's finally making his first appearance on my podcast because I've got a lot of questions from my listeners about IV's and stem cell infusions, and any d all of which this guy's an expert in. He's he's gonna blow your mind is a very broad range of knowledge on these topics. There's just a few select people who I tend to either text or Facebook message back and forth with about a lot of these health concepts. And he's one of them. He's one of the guys who I definitely listen to when it comes to health advice, and specifically some of the cutting edge medical concepts that can help us to live longer and to perform a lot better. So his name is Dr Craig Conn ever, and he's a founder of what's called con ever wellness in Charleston, South Carolina. He's been doing this for almost two decades. He does what is called like I mentioned performance medicine. Everything is science driven. Everything is tested, and he's also the founder and creator of fast vitamin IV and these any D protocols as well as a program that will talk about today called brain, refuel. He works. With navy seals and fell PGA NHL fortune one hundred exacts a whole bunch of celebrities and TV personalities who we actually are able to talk about on the show due to patient physician confidentiality. But regardless I happen to know that he's working with with some pretty high level, folks. So he is he's definitely the man when it comes to this stuff. So Dr I ever welcome to the show, dude. Thank you so much Ben thanks for having me. Yeah. And I just threw out a term that I don't think a lot of people are familiar with. So I figure it's a pretty good jumping off point four us. And that's this. I. Performance medicine. So what is performance medicine? And also, I'm curious how you got into just being you know, physician. How'd you kinda get down the road of doing what you do now? Yeah. I mean, it's is a good question. So I'm family medicine train. So after my residency did something unique in that. I wanted to practice medicine my own way. So in my own practice and quickly dove into this integrative alternative, you know, one of the main things that drew me to that. Whereas these IB's which we'll get into, but you know, practicing that type of medicine which a lotta practitioners aligned with now more of the functional medicine alternative medicine. It made sense to me. But there was also this element that I didn't like or don't philosophically the line with in terms of functional medicine it's on this like robotic. It's almost like we're robots in everyone has to be the same way. And dawn Monday was you know, we're humans who were in our health were actually trying to perform best. How can we help people not only live longer have all your life? But also performed better. I think that's what most people are lying to anyway. So that's kind of the edge. We took with that. Not just we want everything balanced and functioning, well, we want to help you perform your best. So what point did you get into this whole idea of using IV's? Yeah. So you know, I vs. We started early and what really stuck out to me with ivy's is we're able to move the needle with folks very quickly. And so, you know, in in the world, I, you know, work in I see a lot of are used to and still do actually see a lot of complicated medical problems people who are really sick or on multiple medications who've seen lots of doctors who are not getting anywhere with conventional medicine. What stands out to me is that what most doctors forget about is what most people want. It's just feel better. Right. Like, that's that's it. And they can jump on board with all these other plans games we have for them. And so I've ease specifically nutritional ivy's in my opinion are the fastest way to move that needle. And so that's what I kind of started focusing on sled to a host of other therapies and whatnot. So with ivy's why is it that that? They would be more effective. And I understand that that any doc listening and might yawn at this question. But I think a lot of people really don't grasp it this idea behind you shoveling some into the bloodstream versus say taking early. You know, the the number I use twenty percent. We only absorb about twenty percent of nutrients or early. Let's through supplements that's referred. That's an average. But if you're not well less sorry to interrupt, but like less if you have leaky, gut compromise, gut imbalanced, gut flora like you'll you'll get some people who Zorba almost is people who get a as fat bastard from Austin powers would say, you know card in their crap. But the, you know, you look at your stool, and you've got a whole bunch of undigested food matter a lot of people will even see like the vitamin capsules that they're taking and their stool there are so many people who I think absorbed near nothing from their food. No, I agree with that. And so if you're only joining twenty percent, or or like, you mentioned a lot of people less than that. And we verify this because we've done it on over the years time nutrient testing on this every patient becomes a patient. And so we see okay, you may be taking all these vitamins. South wants that are quote, unquote, good for you. But in your bloodstream in your tissue. You're not absorbing it. And so when we do that. And we've done that years, we say, you know, what it doesn't make sense to keep throwing all these capsules in pills at people. And so, you know, from a very basic science standpoint when we give something intravenously the absorption rate is much higher close render percent. And what I tell people to simplify, you know, pneumonia is I think six or seven leading cause of death in this country still prominent disease for, you know, a lot of people every winter for most people we'd give oral anti-biotics we can't treat it orally. They have to go into the hospital wi- to get intravenous antibiotics because they need that absorption. Get those antibiotics to the bacteria in their lungs to treat that ammonia will same thing with IV nutrients, getting his Ivy nutrients in in quantities that are much higher than we ever could. With an oral supplement or food. Yeah. Zeynep UB said for vitamin c like I I actually right now go down to Dr Jason west clinic and polka Telo Idaho into a high dose vitamin c injection. And when I say, I I mean, I know it's like, you know, I I guess it's would come out close to one hundred thousand milligrams of vitamin c and put that in perspective for folks, typically, a high dose wurley is like two hundred five hundred milligrams. So literally hundreds and hundreds of times the actual amount that I could even absorb orally without gastric distress. That's the thing with a lot of these molecules is even if some of them are getting absorbed to get to the level that you'd wanna get, you know, for me, I do that because of some of the research on vitamin C, and it's affected on auto immunity, its ability to be able to protect against cancer, and heart disease and a few other chronic illnesses. I mean, saturating yourself with scorebig acid, despite some physicians thinking that that's bunk in that. It doesn't work. I actually have seen some some pretty good research out of. For example. You know, the Linus Pauling institute that that compels me to actually do a regular high-dose vitamin C, particularly for my immune system. And so that that's a perfect example of a case where I would just, you know, there are good whole foods base forms of vitamin c. And of course, I can't eat Kiwis and oranges all days all day long. But for for me to use better living through science news, mainline a whole bunch of the stuff into my bloodstream and walk out feeling like superman. There's a night and day difference between that and me taking like high dose vitamin c orally assure and you bring up a good point about people not believing. I think people don't totally get certainly with IB nutrients. We we are not talking about doing double blind randomized controlled trials like you're in the pharmaceutical world. So we may at some point have clinical data in actually keep went out with bite in see entering vitamin C me do have clinical data, but the rest of it. We don't so we're dealing with a ton a ton of ton of anecdotal. Data which to me works. Very well like you said there's date Johnny veal, and I can tell you years and years of patient same thing. And and so it's tough for people some people especially that the mainstream the academics. As will you have proven it. Now, we haven't. But there's there's a lot of a lot of goals one. I mean for me, particularly when I return from jet lag. I opened up my refrigerator, and I've got that little ziplock bag you send me with the with the IV's. And I mean when when I one of those after about of hefty travel, and I want to get into the actual ingredients and some of the active ingredients that you put into them. I mean, I feel like a million bucks night and day difference. Then when I add the NASD on top of that. And I've talked about this before in a podcast. I mean, I can this. This might not be healthy. And I do try to sleep seven to nine hours a night, but I can wake up and crush the day on four to six hours of sleep. When I'm using these NASD IV's, and it's it's almost unfair. So I don't wanna make this sound like some big sales spiel for issues, but I'm just you know, kind of backing up. Any goals? One experience. The I've had. So I want to talk about these ingredients like what's actually in these issues. What are the actual formulas that you use? And why? Yeah. So we'll came about we used to do a lot of IB he Latian with calcium EDTA and those IV's were three hour protocols people sitting in a chair for three hours and a long time ago. I got my hands on the European administration of calcium ETA, which is three thousand three thousand milligrams push. That's ten second push. And when I started you that this patients felt better their laps reflected much being my office for for three minutes versus three hours. And so I started thinking, you know, and again this time people were doing these vitamin IB's like they are now wasn't trendy weren't all these IB centers. It was people who were sick people kind of fifteen things like that. So I thought we've got to be because these ivy's works of other feB res away. To do this proactive, Lance that reactively, and I'm lucky I have a lot of patients who like to experiment. We just tried it out in terms of different nutrients, and you know, would use a hosted different vitamins, minerals, lots and lots of we know acids, and we just tested and by tested years in years, thousands of thousands of patients really documented what works and what doesn't work. So Craig we were just getting into the actual ingredients of these IV's because if I understand correctly, there's kind of like some different mixes for specific goals, and I'd like to take a deep dive into these actual formulas and what they're designed for. Sure. So, you know, some of it was based on since we do a lot of nutrient testing, you know, the three big arenas where people are most of or most commonly deficient would be vitamins minerals like magnesium, and then amino acids, and so when I put this together, I thought let's let's shoot for the low hanging fruit. Route because that's what people need most. And we also wanted to use things agents that are water soluble because you know, we really don't want to deal with anything in. Honestly, it's you can give fat soluble nutrients intravenously? But you're talking about a central line and things so gets it's so much easier. Just to do with water Cybele nutrients, very very, very safe. Meaning there's no ceiling in terms of a lot of these things we could see you can give you know hundred thousand two hundred thousand milligrams. If you do it, right? You're not going to run into any safety issues. So the core of all the formulas. We have has those three arenas included a full array B-vitamins so be complex which has led him and B one B two B. We use a lot of vitamin B five primarily because a lot of people walking around today or stressed out. And have adrenal issues in vitamin B five seems to be the most important b vitamin for adrenal health. We use some vitamin B six we use methylated b twelve kinda rounds out the B vitamins. Okay. By the way, is in vitamin b twelve is not nicotinamide right beside your thinking of vitamin B three. That's right is vitamin b three niacin or nice cinema, and we chose Nias cinema. I'd which is like a chemical cousin to niacin because nyah cinema. There's a host of data saying held it helps with mood better than just niacin. So nice cinema. People. Could you know, people are thinking about taking something you could take nice cinema it orally and get a nice bounce to your mood helps with people who are depressed or feeling kind of blue. So nice cinema is what we chose of. For but and be three. And then any d is a chemical cousin to those as well. So we'll get into that. Okay. Got it. So you got your whole vitamin b complex and by the way, before we delve into the rest of what's in here is this all in just one like as a one IV or or do people have multiple options for the type of IV that they get. So you know, we we have a couple of different formulas. But by and large we do best with our main what we call our core formula just seems to be what what people kind of aligned with and get the best results from. So that's what you're referring to right now as you're describing these ingredients all these things are in the courtroom. Okay. Correct. Yeah. And and then in terms of minnows we use. Oh. And you said in in terms of one IV. Yeah. So one of the keys to what we found over the years is what separate all the other, you know, conventional or even nutrient IV's is we give this as a push in through our testing, we found that when we push these nutrients and by. Push. I mean, thirty seconds forty five seconds, sometimes sixty seconds versus forty five sixty ninety minutes. We got a much more robust response. So the total volume that we use for the these ivy's only thirty CC's. Yeah. Versus a drip by maybe five hundred thousand CC's, which is mostly water. Right. So our idea is we flipped the script. We focus on the nutrients, not the water. Yeah. And I think that's also important for people in because I get called out on this. A lot of people are like you're legally doping right because I compete and Spartan races. I have a lot of like triathlete to listen in a lot of U of C fighters who listen in and a lot of these folks are concerned about the issue with ISP being banned by WADA, but the thing is and all the all put a link to this in the show notes. If you guys wanna see what the water description of this actually is you're not supposed to get a fluid volume of IV, drip. IV that's over one hundred milliliters we're talking thirty amounts. You're not like sitting under a big bag of fluid for fifteen minutes or an hour or something like that. This is literally like this tiny little thirty m L push IV that takes his cry just said, you know, forty five to sixty seconds to push into your vein, then it's done and there's nothing illegal going in. It's basically like taking a multivitamin, but you're putting the multivitamin into your vein instead of pop it in your mouth. Yeah. Exactly. So for really for any, you know, professional sports entity, you know, who they all seem to follow somewhat with the water. You saw recommendations, you know, their official statement is like you said less than one hundred C C's of fluid and there and as long as you're not using any, you know, dull trading substance, which we don't use. We're just using vitamins minerals amino acids. So this is technically the only way for people to professionally get an IV vitamin Ivy. You just have to be less than that fluid quantity. Yeah. Yeah. Okay. So. You have the full vitamin b complex that you got into. And what else is in this core formula, we use a lot of magnesium we use a full gram of magnesium, which which at first of lush scares a lot of people because they think will that's going to, you know, bottom people out in terms of blood pressure because magnesium surveys die later. But again, I think that's, you know, the conventional teaching is with any of these nutrients in most things in general, you have to go slowly, right? Like, that's how the teaching is. So there's all these IV courses that these doctors put on across country, say go, slowly, don't your take the vein. Don't harm the patient, and we found just the opposite. When we go faster people get more out of it by more out of it. You know, they they're sensible beings increase their sleep is better that recovery from exercises enhanced they just feel better overall. There's an amplification to things so we are very very comfortable using a full Graham magnesium. And to be completely honest. We've never ever had an adverse reaction like never ever. We never had anyone. Call sitting ahead to go. The ER got a rash got shorter breath. Nothing a very very very safe. And so we'll talk about the shortness of breath later, only talk about the NASD to different different based altogether. But heading and keeps keep filling in on the ingredients in these ivy's. Yeah. And then I think a key part to them is the range of amino acids, we use in so early on I started, including these amino acids, and people are familiar with the amino acids, especially in the fitness sports world in terms of like post, workout drinks, they'll they'll get their way protein or they'll get their visa as or look get their gloomy, and we use all of them intravenously. Now, we don't need to use as high dosages right because they're being absorbed intravenously. So for example, we use acetyl L carnitine that I think is two hundred milligrams. Glue to thirty milligrams will use all the branch chain amino acids valley, Lucy ice loosing we give trip to fan tyrosine Syrian all of them are given intravenously. So as a sum total there's about nineteen different nutrients in that thirty CS of fluid, very potent. Okay. So you would basically just take this. And and I know that you guys do it at your clinic where people can go in there and get these things overseeing. But obviously that's horribly inconvenient for everybody listening to fly, South Carolina. Even though I know you have like more intensive protocols. We'll talk about later. So how does this work exactly with like, the athletes or the folks who are like anti-aging enthusiasts cetera who want to just basically get their hands on these IV's and figure out a way to get them administer themselves. Yeah. It took a question. So what we have a it's a growing number of nurses in our network around the country who we've trained to feel comfortable can administer. But certainly there's going to be a lot of other metropolitan areas, which we haven't tapped into yet. And so, you know for people interested what we do is. We just make sure that their nurse is trained in how we like to administer this not that this is technically difficult, but it's. It is very different than administering any other type of IV. And so for us that safety comes first, and once we kinda sign off on that, you know, make sure talk to the nurses just run through a little training protocol. Then, you know, people wherever they are can purchase these IV's hook up with their nurse and have them done, you know, once or twice a week. Okay. Got it. The the part about the the nurse practitioner, or does this mean that if someone gets the IV's they would be able to get a nurse actually come to their house, potentially. I mean, that's when when it works. Well, and so, you know, the different professional athletes are high octane people who are already doing this. That's that's what they do. Right. They don't wanna be inconvenienced. They say, hey, we just started with one of the Houston Texans on on Wednesday have a nurse in Houston. It's exactly that the happens. You know, they get a group of guys together nurse 'cause the house and ten minutes. They've all been treated. Yeah. That may sound fun. When I go and hang out on it. I know on it uses a lot of your IV's. They. Just have a nurse practitioner there who comes by on which day she comes by. But she administers the NASD should ministers the push vs. And you just sit there and a chair, and she doesn't then she leaves that that easy alone unless you have a friend who's an EMT or a doctor a paramedic or something like that. And then you're good to go. So they can just do a four. Yeah. Okay. So the next question that I have for you is you also have this thing called brain, refuel, is that also an Ivy. Yeah. So brain, refuel is really the combination of an inter inter Venus entity, plus plus the fast vitamin and so years ago when I got my hands on the NFC protocol, and if we back up a little bit, you know, NASD be three vitamin derivative. By and large is used mostly in this country for addiction. That's how it grew up from the nineteen thirties. Actually that was the science then was helpful for addiction really turns off cravings. Whether we're talking opiates alcohol, you name it almost better than anything. And it does it quickly. But those protocols were very long arduous ten straight days of intravenous entity in each protocol lasted excuse me. Each day would last six to eight hours, which is crazy. And so when we got our hands on the protocol, the first thing, I did was say there's no way it's gonna be feasible for most people to get the benefits if it's gonna take six eight hours people just won't come back to the office. And so we did a lot of testing in my office. Again, I I'm lucky I have a lot of patients who like to experiment, try stuff. And so we played around with all the different dosages and came up with what we call what we think is the sweet spot in terms of doses. Where people will get the benefits, but be able to tolerate the IV in in really. Most people that drip takes about an hour hour and a half. That was the first big change we made, and you know, if you talk to the people the original people who brought the NASD IV protocols to this country, and there's there's one gentleman in particular who who purchased the distribution rights for any d- back in around two thousand five or after at that time, there's only one company in South Africa, making N G and injectable entity. And the thought then was that any D has to stay in the body or the only way it'll be effective. Is it stays in the body as long as possible, and we don't we don't believe that to be true at all that doesn't make much sense. So we, you know, we encourage people to go fast as they're able to for most people works out to being out or hour and a half. That was the first change. We made the second change. We made was energy cannot be mixed with any other nutrient. We put it in Stanley, and it has to drip in. But then we we pushed at the end the fast vitamin which has a host of really like. Amino acids things like loot Amine acetyl L carnitine, which help transport the NASD into the mitochondria or into the cell to get to the mind conjure. And so that's really what brain refill is is our naming of the combination of injury entity in the fast, vitamin push. That's exactly what I've been doing. So I do the NASD once a week, but as soon as the NASD finishes up, and I realized that that again as I've already worn people. This is not something I endorsed doing. But I literally just unscrew the same syringe that I used for the NASD and screw in the fast vitamin IV ended that same butterfly needle. And then just just push it in right after the whole thing start to finish takes me about twenty twenty five minutes to do. And and you notice a big difference. When you follow up the NASD with the IV, you still notice quite a bit with just the NASD. But man, it's like rocket fuel when you combine it with the with the vitamin cocktail right after. Yeah. And. You know, the reason I came up with energy pushes, you know, there's a there's a lot of good hard science data about the role of any D in the acute setting of a concussion. And so I thought you know, how great would this be to be available? Whether it's on the football field hockey rink the battlefield for someone who gets concussed and to be able to immediately give them intravenous AD because the hard science supports that. And so that's really where we came up with the push. And then it really became, you know, a novelty because it's it's really challenging to get through especially if someone's never had any sort of intravenous NASD, it's uncomfortable to say the least. Oh, yeah. It's it's very uncomfortable. I mean, you obviously doing like the traditional six to eight hour sitting in any D clinic getting the drip IV people complain that sometimes they feel a little bit of like a butterflies in the stomach or a little bit of pressure in the chest. But do the push V is different. Experience altogether. You know, when you do it for an hour via drip, IV, you you feel when you do the push v. I mean, I have to box breathing going to like this deep meditative state, and I'd I realized this horrible advertising for an eighty push IV. But like I bring I bring like a trash can next to my chair while I'm doing it. So in case, I need to Pook. I it's almo honestly, it's almost like a form of meditation. It kinda increases your pain tolerance. And makes everything you do that day seem a lot easier and within like after you do the NASD, and then I follow that up with vitamin by the time. I finished at sixty second vitamin push after the NASD pretty much all the stomach queasiness is gone. But there's about there's twenty minutes of start to finish in twenty minutes. And I'm just box breathing. Typically, I put on some peaceful music in my MP3. player to kind of like distract me a little bit. And then I just push it. But yeah, it's it's difficult. Why is it? Why do you feel that way? Yeah. I mean, so one of the keys I think to any which I think most people don't totally realize. So when we give people an e and this is going to get into the technical side. But when we get people NA de we increase the NASD to NADA trae xio, and that stimulates a process called mighty drill vision. Vision is splitting. And that is the quality control where were cleaning up the defective might con- drill DNA. And really this is the true benefit of any D because this is really how we, you know, read our body of potential cancer, we clean up again defected to contra DNA, and that process is a very negative energetic process. So that is why we think, you know, we get at those kind of harsh feelings, and you know, I like people to experience those feelings so here in our practice in everyone we work with around the country. We don't like to dampen that down, you know. I know there's a lot of clinics who say, oh, we're gonna. Use this agent or that agent. So you don't feel it. We're gonna go as long as possibly she don't feel anything. And I tell people I want you to feel it because I want you to understand that you're actually doing some housekeeping for your cells literally, and that is the true benefit of energy. Hey, I wanna interrupted eight show to tell you about Birdwell beach britches. I tried Birdwell beach britches. I don't know why talked like a redneck when I talk about Birdwell beach britches. But basically what they do is. They take the same stuff that they make sail boat sales out of and they have developed this stuff called surf Neil fabric, which is a two ply nylon fabric that can survive rocks, grapes and reef slashes and tons of wear, and they literally were inspired by the sales of these boats, anchored at California's Newport Beach since nineteen sixty one they've been making these britches for those you don't purchase are there like shorts basically at their Santa Ana factory and crafts people have been working on perfecting. These britches for over forty years. So you don't get britches. That are much more bricky than this BRIC brick BRIC brick bridge bridge bridge. Yeah, that's right Birdwell beach breasts just paid for me to say Britsh seven times. So. Anyways, the cool thing is that because these things are so tough if a stitch or a seam or Gromit breaks, you send it back to the factory, and they'll fix it lifetime guarantee, which means that, you know, maybe twenty years from now if they're getting a little your red short, again, all pinker blocks forgetting great sent him back Birdwell just send you a repaired pair. I don't know if they send you a new pair repaired pair, but doesn't matter. Don't amazing company and the shorts are amazing. And I'm saying the word amazing too much. I'm just going to cut straight to the chase here. You get ten percent off anything from Birdwell. You just go to Birdwell dot com and use discount code, Ben. That includes a lifetime guarantee, and includes free shipping over ninety nine bucks. So Birdwell dot com. B I R D W E L L, Birdwell dot com and use discount code. Ben this podcast is also brought to by go Shas organics, go shes organics what they do is. They take raw Honey. Like ro organic Honey if you've never had rar Ganic Honey that alone is a fantastic treat. But then they blend it with Fido plankton and medicinal mushrooms and adapted genyk herbs medicinal spices superfoods, and even this special kind of bio absorbable high quality mineral called monetize mineral, they put all of this in the one tiny little meuron glass jar. You can keep this in your pantry. You take a teaspoon of this stuff? It's like rocket fuel. You can start at a tease you can start into coffees. If you're like me, you can just eat it straight out of the jar. It is a SuperFood. It has antifungal properties Alkalis properties incentive IRO, ten bacterial. So it's great for the cold and flu season. That's coming up on us right now. It's got products probiotic soon. Got post -biotics in it enzymes, everything it's it's like everything you need like an astronaut meal, but a healthy astronaut meal in a teaspoon. They should have called it astronaut meal, and I probably would have been fired from the marketing team. I tried to do that. Anyways, though, it's called go shes organics. And this product is called odd Nova odd Nova you get ten percent off on it. Very simple you go shes organic dot com. That's G O S H A S, go shes organic dot com and use the code Ben ten percentage sign like Ben one zero percentage sign that automatically get you. Ten percent off over at Gaucher's organics dot com. You know, what's interesting seems to kind of back that up anytime that I've been beating up my body a lot especially when I do this after I returned from a hefty bout of travel. It's more comfortable if I'm sleep deprived. It's more uncomfortable. If I'm stressed out. It's more uncomfortable. But if I'm in kind of a good place, mentally and emotionally, and from recovery standpoint is not that bad. I actually saved my injections when I can for when I'm already feeling pretty good because it's so much easier. You know, and maltreated tried a couple times when my like, my kids are back from school and things are happening at the house, and there's like noises around and people rushing, and it's horrible. I it's literally like trying to to meditate in a fricken subway with trains running around. It's it's difficult. But the some of the breath were tips that you gave to me listening to the music all of that seems to help quite a bit. And then also just knowing that this too shall pass. Right. Like like when it's over it's over, and you feel like a million bucks. It's kind of like a like, a workout. Like, it's sucks during work out. A lot of times same thing with a sauna session like a hefty out in the sauna kinda sucks. I wanna bang down the doors and climb out of that thing because I'm sweating so hard and feels like my whole body's on fire. And then when I walk out of sauna, I just feel amazing. So it's kind of like a lot of things in my, you know, you gotta put in the hard work. And then once you put in the hard work, you feel pretty good afterwards. Yeah. I think that's a good way of putting it, especially with the workout. I really is like you're you're working out your cells. And I think though, if you can, and that's what we try to teach people in educate people hang in there, and the I n eighty treatments always the worst. Because people psychologically of never felt these types of pains or discomfort. But after that, you know, not only do, you know, it's going to end, but you know, it safe, and you know, you're not doing any harm to your body. Just like with fast, vitamin, you know, we've never had an adverse reaction within a D. Meaning yet, it's uncomfortable. We expected to be uncomfortable. But nothing bad happens. We've never ever had an allergic reaction. No one's ever gotten really sick or gone to the emergency room. Nothing. Like, that's a very very safe. Yeah. No, the absorption issues. Of course, something that's come up quite a bit on this podcast on it goes back and forth between producers of the supplements nicotinamide right beside her and are most of whom will will claim including Dr Charles Brenner who had on the podcast before. And by the way, I'll put a link to all my previous podcasts on an ID. If you go to Ben greenfield, fitness dot com slash I the podcast. That's where the show notes are going to be for this. And I'll I'll link to Dr Carver's website. If you wanna order IV's or anything like that. But anyways, Ben greet with finished dot com slash. I the podcast. That's where that'll be the thing about any d is that of course, we have these and our supplement manufacturers claiming that any D when administered the IV is not actually absorbed into the cell. No, you alluded to the. Fact that not only is absorbed into the cell, but it's absorbed. Even better when you follow it up with something like a vitamin cocktail IV. But do you have any research actually back that up? Yeah. I mean, this is an article I found I think the the main researchers from university of Pennsylvania that was published I think in ah find the day, but it was it was two thousand eighteen and basically what they showed is is they wanted to find out this issue. The title of the article is nicotinamide identity. Dynamically tide is transported into mammalian might contra. And basically what until they had published this article there's just been some references of any D being transported into lower life form, so yeast, for example, they thought okay, there's an any de transport molecule, but we have in dented that molecule in in mammals, and humans well in this article, they did and what what is so awesome. As they they've shown clearly in this article out. Outlines the whole process how any ideas literally taken out from outside the mighty contra and take an inside the mighty country by a certain transport molecules they weren't able to clearly identify what that transport molecule is. But they were able to clearly identify because they were able to tag the NASD molecule outside the cell, and and they they said the concentration inside the cell. So they don't want to know it all started interrupt like like anything about the identity of the actual transport molecule, right? That's still has to be law. It seems to me that that would be a pretty profound finding because this is something that if they did find that out seems like it could be a compound that you could potentially include in like the afterwards, or you know, or even people who are say like supplementing with some form of an arc could supplement with something like that to enhance absorption. Oh, absolutely. I think that's we're waiting on. That's that. That's the study nicotinamide adenine nuclear tide is transported into mammalian motto. Qendra? It's the one referring, okay, I'm going to link to that in the show notes for people to read. So basically what it turns out based on? This most recent research is that you can restore depleted mitochondrial AD levels, and they crossed the plasma membrane any d- does and enters the mitochondria directly cracked, and what they also showed was that you know, that it was it was more profound or greater response. When there is a higher gradient outside the membrane versus inside, the membrane which seems to go right in line with what we feel when we give intravenous AD because we are loading up. You know, the extra cellular outside the mitochondria space with any D, And then that energy is being transported right across the membrane into the mitochondria where it's going to be used to make ATP energy. And they are also seemed to allude. Of and the the, you know, any D precursor people are not gonna like this. But they allude to how that is a much more efficient mechanism than using any sort of any precursor in that article fascinating. Now, you mentioned that the IV cocktail. And this is my last question on NA NASD is one way to enhance the absorption afterwards. I believe that at some point as we were text messaging back and forth, the past few months, you had mentioned a nut was at fossil title searing. You had mentioned to me as being something else that could be code ministered will faucet out choline. I'll tell you going. Yeah. PC puzzle. Choline we use sometimes. But as a pre treatment for glued Afyon, and what we'll do is. We'll we'll put some phosphate choline in the syringe will draw back the patient's blood agitate their blood mix it with the fossil L. Choline push that into the vein and then immediately switch out. Syringe and push included island in the fought. There is the faucet off Coleen makes this membrane more slippery about making it more slippery, you allow things to come after it to, you know, get into this all better, and we've tried that a little bit with with any g you know. I think there has been worse. Some more work done. You know, interestingly another agent, which we're starting to recommend is the is quercetin because quercetin we get into this about other things with how quirks in works. Quercetin. Seems to turn off one of the enzymes that destroys n D extra sailor in the exercise of their space. So I've had a few people try that recently where we'll give quercetin Orly at the same time as giving intravenous NASD, and we're going to kind of chart and see how that plays out. See how that works for them. You'll potentially add that to the Ivy as well, if it turns out that it would work. As far as I know so far, no one's the one's making intravenous quercetin. So that that will be a challenge that one. Yeah. I trust. That'd be that'd be I. Yeah. That idea that make it happens with the glue to on that you mentioned though from what I understand is that not to be code ministered along with the NASD crack, so we don't we don't like to give any antioxidants really at the time of at the time of administering entity. And the reason is alluded to before talked about any d- stimulating might contra physician antioxidants will damp in the physician response. And so when we administer glued define we'll do it on a separate day than any d-. There's lots of benefits for good thion, which just don't like to mix the two I began to do that. After you told me, I don't take my glutathione supplement. Neither do I do. I recently interviewed Dr Corinne, Johnny on my show. We talked about genetics and he revealed that both myself and my twin boys don't actually produce glutathione. So he sent me glutathione powder to inject actually that's an IV injection. But before that, I was doing intramuscular glutathione junctions. Which for anybody who doesn't produce clue to on. That's just I I totally understand. There's some people rolling. There is now saying dude how many things you can you can inject. I I understand I get it. But this is just better living through scientists taking better care of the body. And as I explain this to people like if I can be around fifty extra years to be able to fulfill my purpose in life, and to help more people feel amazing doing it for if if that means like once a week, I take an extra, you know, minute to push IV twenty minutes to do an and then five minutes at some point during the week to a Gouda thion. Like this stuff is not that inconvenient, especially when you consider the fact that if you do have some kind of YouTube video or documentary or something you wanna watch where you're sitting there getting the IV fine kill two birds with one stone. So anyways, though, I digress. And I will I'll link to that podcast with with Kareem about Gouda thion in the show notes. But what I do is. I now don't go near that stuff and within twenty four hours before or twenty four hour. After I've done my MD based on your recommendations. And it sounds like what I could do that glutathione is at least include something like fossil title colon. Could I just take that orally for example? I mean, you could. But I mean, it's better to again from absorption, you'd better do that intravenously. So I'll send you some and you can try it. There's been some trouble. Thank you. Good, sir. Up for us. Yeah. There's been some like a lot of these nutrients there's there's waves where it's more difficult to get them. That's what's happened fossil calling. But it should be back in ready to go. And and basically what you'll do is. You'll just as opposed to push ching. I you'll drawback agitate your blood I with the fossil choline, and then push that which syringe push glutathione, and you know, fossil coins. One of these stellar nutrients that helps with deliver helps with brain health helps to you know, with all of our cellular membranes. That people often forget about it's one of these key nutrients, though. Interesting. I know that there are some other things that you do in addition to the brain refuel program, and these fast, vitamin IV's and one that you told me about that. I haven't done with you at all. But that I've certainly done in other scenarios is stem cell infusions. And I'm curious what you're doing as far as stem cell infusions are concerned and how exactly that works. Well, so, you know, for me, personally, I kinda held off getting into the stem so world for a while it seemed like the wild wild west, and you know, last winter about a year ago. Now, the FDA changed the classification of umbilical stem cells bilk stem cells from alive sell to a biologic and gave a three year window for where we could use these cells. And that's where I kinda jumped in because to me umbilical cord stem cells, a really the most potential they are. The the most the freshest the most potent and the the youngest right? So if you take an umbilical cord stem cell, it's age zero versus a lot of people getting stem cells in their forties fifties and sixties cells age forty fifty or sixty and so we'd like how these umbilical cord stem cells work, and what what I do. Because I honestly love any g you know, my research showed that in order to kind of prime the body or one of the best ways for our stem cells to be absorbed, and then work is to up level. The might have conjured because the mighty contra seem to direct how stem cells work, and it something I read something I research said, you know, stem cells are best infused during MIDA Qendra fusion. And so what we do is. We do a three day program where we start in d three days ahead of the stem cells because we want to up level the mighty Qendra. We're going to stimulate muddy Kondracke vision. And then might a contra. Vision than stimulates might contra fusion so by day three when we're ready to give the stem cells, we have those mighty country kind of primed and ready for the stem cells to be received. That's very similar to a protocol that I was talking about recently in that I even wrote a blog post on with Dr Jalan Chen over in New York City who's doing like a muscle gain protocol, he's using coenzyme q ten in a d and injectable stem cells, he's actually using a tall stem cells. Meaning I think he's using like a bone marrow aspiration along with v cells, which are basically like a signaling molecule that that can assist with the with the stem cell efficacy. But when it comes to these umbilical stem cell cords, I have belco Korda stem cells, I have concerns because I have been told that you don't know if it's safe since it's coming from foreign tissue, and that there might be yet on identified Vira. Press' or priante or proteins or other things that you could be injecting into yourself, or I know there are some clinics like east west clinic in Salt Lake they administer them even internationally. You know, what you use for like TBI concussion, and and I've began to steer clear of some of that. Because of my concerns about the safety profile, can you speak do not at all. Yeah. I mean, I think that that comes up commonly when patients say, you know, what type of cells, and that's the biggest thing or are these stem cells filtered a clean, how do we know? It's different genetic material. So so here's what I go back to and I try to simplify things number one the umbilical cord stem cells are immune naive. So they haven't formed any immune antigene city. So you're not going to react to them. Now. Does that mean hundred percent time you want rectum, of course, not because everyone's a little bit different. But by and large and we've done a ton of these stem cell treatments. Now, we have no reactions meaning people aren't having any sort of. Rejection. There's no rash. There's no any sort of adverse event from using the stem cells number two, I think the the main issue that's gonna come up certainly over the next few years is there's going to be a lot of stem, cell, banks or stem cell companies jumping into this arena. Because they say, hey, this is a popular way regenerative medicine, and we have to be very careful of where we get these stem cells from. So there are as I know it several, you know, public tissue banks, a several companies that offer the stem cells, the the, you know, we, you know, for me in my practice. My patients we're going to be really scrupulous about only using cells that come from a very company that's been around for a while who's been doing this for a while. And I think that's an issue. I remember talking to a client out, Los Angeles. And he was I was asking him if he's interested in getting them, and he said, well, he had a friend who had umbilical cord stem cells injected in. Onto his disk one of his disks in his lumbar spine. It got infected using the intensive care unit. And to me, I think that's taking it too far. Like, I think you know, there's there's people who will inject the heart wisdom cells. I think you know, I think there are people who inject intravenously into the spinal cord, and I think that some of that is. Yeah, I'm sure there's hope and potential. I just some of that you just have to be careful of so we're going to be very reasonable about. What we do. We're gonna choose companies that only give us data in terms of how these stem cells or filtered screen tested, the other thing, I'll say is, you know, once these stem cells are taken and made into what is, you know, the vile so to speak they are frozen in liquid nitrogen where really nothing can live. Right. It is it is so called to we're not I'm not concerned as long as we. And this is how we do it. Here. We have a tank of liquid nitrogen or. Keep the stem cells when we're ready to do a treatment. I mean, I just did a treatment this morning. We'll take the stem cells out thaw amount and give them immediately and doing it that way, we don't we don't worry about. Oh, is there gonna be some virus or some pathogen that gets in there? Could there be anytime you inject anything? There's a risk of infection for sure. But I think if you follow a really good protocol and do your homework in terms of the company that is selling you, the stem cells, I really minimize that risk is it regulated at all by the government as far as I mean to companies such as yours or medical clinics mean to actually choose sources that have been screened properly mean I get the impression the wild wild west. But filming on what's going on as far as governmental regulations of that. I don't think. So. So I mean, I think I I really don't think like if you're a doctor, and you order stem cells you could order from stem cell company act. It could be horrible. You could perform, you know, stem cell infusions on patients and potentially using bad lines of stem cells are not doing your homework. I don't think there's much government regulation terms of that. Now what they ask us to do the stem cell companies. We have to fill out a form and document, you know, the batch the lot everything about that where that bile came from and keep that. So that in case a patient comes back in three days three weeks and said, I had this happen. We can go back to that company and say, hey, it came from this vile, specifically, please research this the company we use as predicted biologics, and I feel very confident in every aspect of how they go about their business in terms of showing us data again, and then providing high high quality product and giving us all the tools, we need to ensure the safety of the stem cells, and that's good to know. So basically if people are. Are going out and getting umbilical stem cells. They they they are ideally obtained from a healthy newborn baby they are screened properly. They're stored properly. Correct. And then as well as the doctors who's administering them has done this before in. You know follows a good protocol to ensure that you know, K the stem cells arrive where you take him out of the tank, and they're not just sitting there for two days, you know, room temperature. That's you know, what I mean. Like, it's gotta be done in the right way. You're talking about number one very expensive material. But number two, it is a big safety concern. You know, we'd never wanna put people at risk. You know that that guy out in Los Angeles who had his friend got in the intensive care unit. My comment was I don't I don't think doctors should be injecting inside a disc with stem cell, not having -fornia it. Yeah. That happened in Los Angeles a doctor orthopedic surgeon in. Elected the guys in into a disk intra disc injection because he had a bad maybe a herniated disk, and I just think that's pushing the limits a little bit. So I didn't know about that. So I feel a little bit more comfortable actually hearing you talk about this umbilical cord stem cell infusion. I realized that the screening process was that intensive, but I guess a big part of this. It sounds to me is still that process of patient self education and actually figuring out whether or not the docs, actually getting this stuff from a clean source storing it properly cetera. I think so I think again, I think in the next couple years we're going to see where there will probably be some stem cell companies that go under or get closed down because they don't have good practices, and they're into it to make it quick buck. You know, like anything right like people have shortcuts in this process. We want zero shortcuts we want to the most rigorous treatment. We want the most rigorous filtering screening everything. Okay. What about things similar to what you could inject with any d to enhance any D absorption, like CAIR, Seton or these vitamins or phosphate, title Coleen with Gouda phone, what could you administer along with stem cells to aid in the absorption or utility of stem cells. Yeah. So what we do is part of our protocol. So we start intravenous entity. That's they want. We also start international oxytocin because oxytocin has an effect on the brain to help prime indirect stem cells as well. So people are familiar with oxytocin is going to the social bonding hormone it also increases nitric oxide in the brain. But it also has a role potentially in the, you know, the hypothalamus where a lot of the what we think are kind of the master control of stem cells are regulated. And so we just like to start international oxytocin. We also start some injectable peptide. Ads on at the same time. And that's really, you know, what we found to be really amazing mix or triad is intravenous energy, the peptides as and then followed up by the stem cells. I wanna ask you about the peptides innomax, that's a hot topic. But international oxytocin, I we we can't just skim over that. So this is the the hormone like the trust hormone, the bonding hormone that gets released during sex during breastfeeding during human touch, you're actually administering that international like people snort it. Yeah. We we make we compounded into a nasal spray, and then people spray that into their does a couple times a day and actually must people feel kinda more relaxed happier from just doing that. Again. We're not really using it for that purpose. We're using it kind of from the stem cell aspect, but that's an added bonus. So sure we compound a lot of things internationally because again, you know, going back to you know, you you had mentioned, oh people are going to you should be doing all these injections while I would argue where. Sitting here taking all these things orally that just don't work. So why not look at some alternative delivery systems? And that's what we like we do a lot of things internationally intravenously injections topically because we want to get into the system. That's what matters most there's a lot of research on oxytocin for pretty wide variety of benefits that go beyond like stem cells or uplifting mood. I mean, like, I know it's a potent anti inflammatory. And it's it's something that has been studied for for a lot of different issues. But this idea of administering internationally, I guess in the past the the only other way to do it aside from the naturally should get through sex would be like an injection. It's not something you can take orally. Right. You know and say could we we used to try it as a sub lingual to under the tongue and that just didn't seem to work as well. And so we'd like a lot of international things we make actually a D into international spray. We use ketamine as an intern as will spray. We have a couple of things that we're trying as well that we're putting together we have actually coming up is the NASD and CBD oil sub lingual will try that internees. Yeah. We'll try that intern. As Li as well, I mean, the idea with intern as low as you are you're close to the brain, you have the mucous membranes that are very permeable. So you spray up the substance in it gets right to where we want it to which is the brain. And that's that's the hope now some of it being lost for sure. But if we can again, avoid the digestive track and have a different delivery system and get something that potent that works all the better yet. The other thing is get appetite suppressants confer good for diet. I know that oxytocin neurons in the hypothalamus helped suppress appetite with this one reason. Sometimes I don't know if anyone is actually tried this out. But like if you if you're hungry at night a lot of times, and there's probably quite a bit of dopamine and serotonin play here too. But sucks at night. Like, you know, if I have the option between like having a bunch of dark chocolate and some coconut ice cream. Or having sex. Ideally, both. But I've noticed like after I have socks. Maria for bed. Good like my ties gone. And I suspect part of that is due that oxytocin release. So it's got a lot of interesting uses. I love that you guys are are forward thinking on some of this stuff. So and again, if you guys are listening in I think that that's something that people can also work with you to to have like compound for them right for sure. Yeah. I mean, we work with people across the country, and we do this quite routinely. Again, our philosophy is if we're going to move the needle we have to have agents that actually work, and we're just not interested. He giving people lists of take these sixteen supplements in that just doesn't work anymore. Yeah. Okay. Peptides. I've talked about one fifty seven something you've got injected joints TV five hundred to enhance healing. I don't know if I've talked about on the show before. But there are a lot of these anti-aging peptides, like epithets, Lynn or humanitarian or Motte see that that almost like exercise in a bottle that you can inject subcutaneous Lee around the abdominals for. Both longevity and motto Conroy and also things like that loss and muscle gain. And I'm I'm actually working on a new book on lawn Javadi where explore some of those peptides. But I'm curious what the injectable peptide Jordan ministering along with these stem cells along with an ID to to enhance the effects. We use a host some we use. We certainly is BBC one five seven at just a potent anti inflammatory peptide, and we use it just to stomach -ly. So you can inject it anywhere and get a systemic effect from that probably more than that, though, we use the growth hormone releasing peptides, which are things like IFA Moreland G, H R P six G H R P two. And then we couple that which something called CJ see twenty nine five which is really a fragment of the growth hormone molecule. But what it does is it the way I think about it is the peptide portion, which is will say, I pa- Morland that. And again, a peptide is a small molecule, it's a chain of amino acids. And what it does is? It will go up to the Patou itary gland, which secretes growth hormone, and it will bind to that growth hormone receptor and say put out growth hormone. So we're using the body's own tools. We're not adding anything exotic gently we cannot suppress our Patou itary outlet because we're just giving ourselves a little push. So we we use. I pa- Lindley we couple that was like C J C which helps that growth hormone to stay in the system longer. So you're pulsing it. So we have people do it two times a day when they first wake up in the morning and right before bed because those aware we think you get the biggest pulse of growth hormone anyway outside of exercise or resistance training. And then we couple that with the C J C. It's it's one, you know, a liquid that comes together, and what you're gonna do is post that growth hormone and growth hormone being such an anabolic hormone is going to not only, you know, calm down inflammation help rejuvenate tissue. But it's going to help with the structure of the cells as well. So the way I think about it is we start these peptides start any D as ways to be potent anti inflammatory, a while we're waiting for the stem cells to kick in and then that takes a couple of weeks. But these peptides are really fascinating. Like you mentioned. There's a host of peptides being explored. The other one we use in conjunction with stem cells is this one Kaji h k dash copper, which kind of grew up in the wound healing world. And we have people do that at the time of the stem cell infusion, and they take it for three weeks straight. Because again, the whole concept is we want healing, right? We went rejuvenation and that seems to help promote that as well. So that would be like something to promote things like collagen, synthesis or join hill. Exactly. Absolutely. Yeah. I mean, I think you know, I, for example, I injected a guy soft tissue is back right around his lumbar spine, and he's had her. Eighty desk and nerve root pain fifth set issues, and I think a lot of it with people with their spine as they don't maintain the structural integrity of the tissue around the spine ride. They lose that integrity of the tissue. And then they end up using things like end saids like ibuprofen Motrin, sometimes even steroids, which can come down, inflammation problem is they delay wound healing they make for they destroy and that's a strong word, but they they impair I should say the structural integrity of the tissue. And when we give stem cells like that our goal and peptides were helping to rebuild the structural integrity of tissue to help the sport. You know, the joints the spine. Yeah. Most peptides, not BBC one fifty seven. But most of them are banned by WADA but a ton of pro athletes, use them still because they're so rapidly metabolize. You can't. You can't they're they're not legal. But they also can't be detected. I'm not I'm not saying that I endorse their use or anything like that. But a shocking number. Of folks in like, the the NFL, for example, or any of these more anabolics like frigging like I would I would estimate probably eighty percent of the league is on peptides. So it's it's something that that is widely used in sports because of its potency ineffectiveness. Do you have any concerns because I knew we'll probably get this question about, you know, undifferentiated cell growth and the potential for carcinogenicity or something like that along with the use of growth hormone. I think growth hormones tricky. I mean, we we have some patients on growth hormone. I think what happens with growth hormone in my experience, and I've been using it with patients for a long time is patients get the sense that if a little is good a lot is better. And I think that's where people get in trouble because I think you can use a very moderate dose of growth hormone in a reasonable way without manipulating that hormonal pathway, and so if we stick to that, and you know, the issue is, and this is a interesting topic. Anyways, you know, what happens with, you know, insulin growth factor one or I G F one. And I know there's this. There's this kind of rivalry almost with the fitness versus longevity in terms of fun. And I think with growth hormone, you have to be careful because if you exceleron IGF one too quickly you can signal for cell growth at times, you don't want cell growth, whereas the peptide. Ads don't seem to elevate. I one in less. I mean, there is peptide of of idea when I have a patient on right now. But you really with the peptides, especially the growth home, releasing peptides? You're not increasing. I Jeff one you're just making your idea one more efficient, and that's the big difference. So P who use growth hormone, the challenges in my opinion. We do is we monitor their levels because if we see them rapidly going up, we know they're potentially is yet. That's the cell signaling telling the cells to accelerate growth where we probably don't want that. Okay. Got it. Yeah. So basically, you wanna test pretty intensively under supervision when using these things not like with growth hormone. Yeah. I from me from a website and just administer willy nilly. Yeah. And I think of growth hormone being much more valuable if you're seventy eight years old, right? And you really do need growth hormone replacement right? Like just like testosterone declines as we get older, growth hormone, certainly declines. But for my patients, I wanna reserve that till the variant, I think the peptides offer way too much potential. They're not as potent. But again, we're fine with that. Because we don't want to trigger this cell signaling their the cell growth at times, we're not supposed to have cell growth, and the and the and the peptides don't do that they make your idea of one more efficient, but they're not gonna accelerate your idea fun. And I know that because we've been using them for years, and we measure people all the time. Okay. Good to know. I again, as you guys are listening to me, and we're going through this. I'm taking notes, and if you go to Ben greenfield, fitness dot com slash IV podcast. I will link to some of the programs the Dr Khan ever has for example for his umbilical stem cell program. You can go to his clinic and do the stem cells combined with the NASD and the injectable peptides that he was talking about. He's also got a programmer, you can do any D V therapy pretty much every single program. He has he's giving every single one of my listeners a twenty percent discount. Count which is massive on on any of these protocols, including just like ordering the IV's to your house. We didn't want the flight under the clinic and using nurse practitioner for some of this stuff. But one of the other things that you have is this idea of distance medicine you doing distance medicine and phone calls. How exactly does that work? Yeah. I mean, it doesn't work for everyone. But I think in this day and age where we have technology is cell phones, and we can text and call Email, it can work really well for people who want that kind of advice in terms of, you know, whether be starting peptides or nutrition or what what really ends up happening practically as we'll start working with them remotely. And then they will eventually come here to to Charleston to be patient person. And so it's really just starting off, you know, and it may be three months six months until they're able to get here. But we'll start them off with different programs in terms of counseling them giving them advice again, not for everyone. But for a lot of people it's hard to find a doctor who's open to these kind of concepts. And so they're looking for ways to again, optimize their health and performance. And so we want to offer that service, okay? Now, what about the idea of training, other physicians to same kind of performance medicine that you do you have a lot of docs, who listen and some of the stuff that they've never even heard of before or wanna do kind of like what you do in their community. But don't know how to get started. Tell me about your your physician programs. Yeah. And so one of the things I really enjoy doing like, you mentioned is is working with other doctors in. I think doctors are in this interesting place, especially the ones who understand optimization of health and performance, and there's not a lot of us. And and, you know, a lot of it is being led by other people who, you know, for example, as a family medicine, doctor, I can help people optimize their health, but I can also clean up when they get sick. Right. And I'm here to deal with kind of both sides of the aisle. And I think doctors who embrace that can do very well and can offer a tremendous amount of unique advice. Is for people because we we have a different perspective. Right. We know what sickness disease. Look like not that we focus on that. But we know how it works, and we can prescribe medicine if needed and for the doctors, then want to take it to a different level in shift their mindset from a disease or any place to health and performance perspective. We offer different training programs from phone calls to personal that come to our office. Do a full day or more of training where we go over everything, you know, were open book we like to provide all the protocols that we use that we've discovered to help physicians in honestly, we like to collaborate because then these physicians go out in their communities. They try things and we learned from them. And so it's just building a network of physicians who want to collaborate together and do things differently than the, you know, the regular conventional doctors. Yeah, I mean, this is cool. It's cutting. So I mean, I I really dig it. And as you know, I just I love all this cutting edge medicine, and I want to warn people once again because. I know I get kicked back on us. All the time. I'm not saying like order a bunch of IV's and start sticking stuff in your veins willy nilly like you have to proceed with caution. I rose I'm kind of a cowboy with some of the stuff, but. Proceed with caution. And that's why I want to get Dr Connor on the podcast talk about how you could do some of the same things I'm doing, but do it under medical supervision or do with the nurse practitioner? And I think a lot of people are special very interested in at least the vitamin cocktails in the NASD. I would save all the stuff we've talked about. Like that stuff is the most simple straightforward and both -ffective in Lille to just do right away for anybody. So this this is all fascinating stuff. I love it too. And I and I tell people all the time like if you're really interested in optimizing, your health and performance like any D has to be a part of that conversation because any d is so foundational on the CEO level beyond hormones beyond nutrients NASD is really critical. And I think we are just at the tip of the iceberg in terms of understanding how any d- works and all the benefits that it that it provides. So there's a host of of ways for people to opt. Demise their health and performance that are well beyond just taking oral supplements in eating a good diet. Yeah. Yeah. It's better living through science, baby. I well. I'm gonna put links to everything over a Ben greenfield finished dot com slash IV podcast. That's Ben greenfield finished dot com slash. I the podcast. Check out the show notes. Their own linked to all my previous podcasts on NA NASD. I will give you guys. A you could just go to con- Ivor wellness dot com. It's Kate O N I V arcana ever wellness dot com. Anything there if you use discount code Ben will knock twenty percent off the umbilical cord program. The NASD therapy the distance phone call with him the physician phone call where physician can hop on the phone with him the IV's code. Ben covers all you twenty percent off of anything there. Be can also go to the show notes world linked to everything that we talked about two, and that's been greenfield fitness dot com slash I the podcast while Dr Khan ever first of all, thanks. We're coming on the show. Can't you doing and keep us all posted? All this crazy, new cutting edge stuff, you're looking into like the the care Seton. And and peptides and everything else. Like antennae come across something interesting. Let me know pass onto the audience. Absolutely. Thank you so much for having me. It's been a pleasure. Cool folks on been greenfield along with Dr Craig Conn Ivor of con- ever wellness dot com, signing out from Ben greenfield, fitness dot com. Have an amazing week. While more go to Ben greenfield, fitness dot com. Where you can subscribe to my information packed and entertaining newsletter and click the link up on the right hand side of that webpage says Ben recommends real see a full list of everything ever recommended to enhance your body and your brain finally to get your hands on all of the unique supplement formulations that I personally develop you can visit the website of my company kion at get K I O N dot com. That's get K I O N dot com.

NASD Ben Dr Craig Conn nicotinamide Gouda thion South Carolina NASD Adidas Facebook Birdwell Kim dot carnitine Ben Greenville soreness bark Heil CDL Mira
This man biologically aged BACKWARDS from 70 to 44 years old in 8 months, here's how...

Limitless Mindset

17:27 min | 11 months ago

This man biologically aged BACKWARDS from 70 to 44 years old in 8 months, here's how...

"This is Jonathan with limitless mindset. And this podcast is about a man who allegedly aged backwards from seventy to forty four years old in eight months. And we're GONNA get into that in this podcast. This is also an article that you can find on my website limitless mindset dot com which is linked below wherever you are listening to this so like. I said this is a case. Study of person who biologically biological age. It's a little bit different than actual age. He h backwards from seventy years old to forty four years old in eight months and I know that sounds too good to be true. If you're skeptical. That's fine so was I. Intel. I saw Lawrence's biomarker data blood tests which objectively measured nine different biological markers. I've been anti-aging obsessed for eight years. And his data blew my socks all the way across the room. I've read hundreds of these too good to be true anecdote reports but Lawrence proves it by sharing his data which I include below four the other data lovers if you want to check out the data if you WanNa see if I'm you know talking bs here you can go and take a look at the article linked below this as I do have his spreadsheets there to clarify this data demonstrates that Lawrence biologically age backwards. I'm not talking about time. Travel involving a delorean or anything silly like that. Lawrence was a pre diabetic. Sixty year old stricken with arthritis. His Biological Age was seventy win. He began reading about an M. N. Which STANDS FOR NICOTINAMIDE. Mono nuclear tied a new anti-aging medicine that your doctor probably doesn't know about but that Harvard anti aging researchers believe is a crucial part of the puzzle of along health span. Eight months later he felt and looked a lot younger biological age. Forty five according to the data. But don't take my word for it. Here's what Lawrence had to say. I quote from him here about weight. Loss and muscle growth quote. My weight began to drop within a couple of days within weeks. I felt that I was shedding belly fat and noticed a visible flattening of my tummy. At that time I also noticed an increase in strength endurance and muscle size by the end of the program. I weighed two eight and I believe I had lost around twenty pounds of fat and replaced it with about ten pounds of muscle. That's pretty good about testosterone. After taking the supplementation I noticed a nice increase in the pep of my step. All of the males in our group have reported a one hundred two hundred percent increase in their to dos Jeroen levels the guys with low baseline levels of testosterone all noticed a market increase in the pep in their step or alternatively described as the EH amend kicking in the guys with high baseline levels of testosterone barely noticed any change to their pep and didn't have the sensation of the kicking in so testosterone increased forty seven percent from two twenty seven to three thirty five about the arthritis years ago. I was diagnosed with rheumatoid arthritis when I was on an the arthritis in my knuckles began to clear in the third week by the third month. All of the arthritis in every joint in my body had cleared talking about sleep quality within the first month. I noticed that I was sleeping. Much more soundly sleeping about an hour longer and waking up really refreshed and clear minded about energy and youthfulness win. I I started taking any man. I immediately noticed a slight increase in energy. Several months into the original regimen of an-and. My neighbors were stopping me and commenting that I looked healthier younger more energetic buff really good etc. I personally attributed my boost in energy to the increase of my testosterone about inflammation. Here's what he had to say. My inflammation markers all improved. C reactive protein dropped a post and awe point. Nine two point four nine tumor necrosis factor improved interleukin. Plasma dropped these last. Three tests were all measurements of inflammation levels of my body. As increased inflammation is tied to aging and a decrease in general health. I was pleased to see my inflammation levels being reduced as a chronological sixty year old male. I was pleased to see my biological age. Had dropped from seventy to forty four like I said about aesthetics and mobility. One of the more interesting comments was that I was moving like a much younger person. After that comment I focused on my walking mechanics and realized that I was walking with a much straighter posture with shoulders. Back chest out and a looser or fluid crooked stride as all my joints were more flexible and pain-free physically. I felt like my body did twenty years earlier and in this article I included a few snapshots of the data from his blood tests. Showing the biological anti-aging markers I actually show nine of the different biomarkers. That linked to the three detailed post that he did online and this was a lunch. Acidy DOT org so the good news is that you can purchase pharmaceutical grade and an N. via the link that I have there in the article I identified a really quality source that does their manufacturing here in the USA and then they have an accredited American spectroscopy laboratory. That verifies the purity of the stuff so that you're really ensuring that you're getting the real McCoy and so it is above ninety seven percent pure and free of additives or toxins. Which is super important. If you're going to if you're going to drop a not insignificant amount of change on this sort of thing now with N. Amid there is a usage and dosage protocol that you'll want to follow to use it most economically and get the maximum longevity. Bang for your buck and I do. Include that in this article so go. Check that out. If you're you know hoping to possibly experience the kind of transformation that Lawrence did that is certainly not guaranteed but I did research this stuff for quite a while. I looked at a ton of things that people were writing and saying about it across the forums on Youtube Reddit etc and I was pretty impressed with the effects that it appears to have. I do hope to try it myself at some point and then I can report back my own experiences with it. What are you giggling about? It got lasted the male tragically. Now I'm not sure we got lost twice. I think it might have just been the one the one time that got lost in the mail. Just just imagine babe are lost package of may be giving some mailman just spectacular. Boehner's right now I can only. Yes yes the customs officers are feeling just a bit more rowdy. Thanks to my thanks to the package being lost. So let's keep this professional. Okay Babe so won't you? You might wonder why the Heck Heaven I heard of this stuff before and what sorts of side effects does it have so n is a natural unpatented anti-aging medicine it's a special form Vitamin B. Three and converts into each entity plus molecule that our bodies produce naturally and. My wife is still laughing for no reason. I don't understand while attempting not to laugh. Get yourself under control this is. This is totally unprofessional in the podcasting environment. What did I tell you about breaking out in laughter? While I'm trying to record a podcast very serious subjects yes well. That's that's because we live in Bulgaria dear listener. If you don't live in Bulgaria your packages will probably be delivered to you. Just you just fine. We live in a very special country where crying. It's like getting packages on the surface of the moon. Okay where was I hear? It's a special form of vitamin B. Three and it converts into a molecule that our bodies produce naturally overtime are any plus levels declined causing aging and disease since its unpatented. Big Pharma isn't going to be advertising it on television anytime soon nor will your doctor be prescribing. It unless they keep up with the latest anti-aging research coming out of places like Harvard and the University School of Medicine in Tokyo. The good news is that side effects are minimal to nonexistent a few places around the Internet people report increase appetite in. There's there's not serious concern with side effects because it doesn't directly hack our biology by stimulating hormones are transmitters. It works by feeding us a little more of this natural molecule the NASD plus molecule that we need for optimal EPI genetic function allowing our bodies to turn on and off the right genes at the right time. It just empowers our bodies to do what our bodies do naturally which all of the chemicals and toxicity of modernity get in the way of. Here's what Lawrence concluded with in summary. Some of the benefits appear to be lasting while others went away. After I stopped taking an overall I felt my initial experience with an was very positive with no downside risk. I firmly believe that I now have a much healthier body and also believe that my body is functioning like a much younger version of myself. Wow that's great. News isn't it and Harvard anti-aging researcher and bestselling author David Sinclair. Phd explains a little bit more about the mechanism of enemy. There's a great video that you'll want to check out. It's just a couple of minutes long. And it was called rewinding the clock on aging blood vessels that is linked embedded and then David Sinclair also did an interview on the Joe Rogan experience detailing his extensive experience with an so. I would actually suggests that people go and check out both of those things because he had some His particularly his discussion with Joe Rogan was really eye-opening and this stuff is not cheap. It's not agreed asleep expensive. But if you're GONNA use it you probably want to make a bit of an investment and take it for maybe a couple of months so you'll want to be as informed as possible and you want to read or suppose you could listen to another podcast. I did a real detailed analysis. Where breakdown all the scientific studies the backup the anecdotal reports like Lawrence's and if you're still skeptical of Lawrence's real-life Benjamin Button transformation. I understand you can confirm his story by reading the exhaustive twenty page on just before where he goes into a lot more detail. Extraordinary claims require extraordinary evidence and he provides it and then I should probably just add as an attendant as an addendum tutis results. Not Typical while using an lawrence was implementing a lot of other smart biohacking hacks to empower his health. His transformation should not be credited to an amend alone however I share his story because I looked at numerous credible bio hacker and case studies that are consistent with the effects that I've described here a single anecdote even a thorough one. Like Lawrence's is just something that someone on the Internet said but when you find numerous credible examples of an effect being imbued by a given supplement if you see the same things over and over again different places across the Internet. You can be pretty optimistic about using so. I'm pretty enthusiastic about an and I just remain very very hopeful that it will eventually get to us here on the planet Pluto. I'm Jonathan with limitless mindset and I look forward to a continued conversation with you legal notices if you or someone you know developed or created a concept piece of content or idea shared on this show. Please email us at INFO at limitless mindset dot com so we can mentioned them in the show notes or provide it back link. We want to give credit where credit is due as a listener to the limitless mindset. Podcast we hope you have and practice common sense. However since some of the content covered in this show deals with subjects of a health legal or business nature this show is for entertainment purposes if you need recommendations of doctors nutritionists or attorneys to console before making decisions that may have health or legal repercussions. Please email us at INFO at limitless mindset dot com.

Lawrence testosterone Jonathan Harvard Intel David Sinclair Joe Rogan USA NICOTINAMIDE Bulgaria McCoy Boehner His Big Pharma NASD Phd Tokyo researcher
#1306 Pushback For The Sake Of Pushback

The Adam and Dr. Drew Show

45:02 min | 6 months ago

#1306 Pushback For The Sake Of Pushback

"Thanks for listening to the atom and Dr Drew Show on podcast. One. Coming to live by live Thursday July thirtieth. Darius Rucker's Darius and friends virtual concert benefiting Saint Jude. Children's research hospital catch an exclusive one time only performance by Darius Rucker, live from the Grand Ole opry stage featuring guest appearances by clint black and Tracy Lawrence, all proceeds from the show benefits. Saint. Jude. So get your tickets today at live x live dot com slash Darius and tune in July thirtieth at eight PM Eastern only on live by live where we really ranging in this show, we'll talk little love boat. Makeup make up and? Then, we'll talk any D. I. I'd say about blinds. Galore, love these guys. They're having a huge summer. scorcher sales starts this week up to fifty percent off everything one of their biggest sales of the year. So HURRY TO BLINDS DOT COM sale ends next Wednesday, August, fifth over two million windows covered a one hundred percent custom window treatments online made your exact measurements delivered right to your door blinds, shades, shutters, drapes, even blinds that guy connect to your smartphone Amazon Alexa device, which I have and my bedroom. Nice. Just do it all all. All by word of mouth man, just make your command up and down. You can have a bill, the blind tool that you can customize your blinds to see what they look like before you ordering blinds, Galore Dot com is all you need. Right? Man. That's right. Blinds. GALORE DOT COM makes it easy to get the designer blinds and shades. You've always wanted without the designer price tag especially during their huge summer scorcher event when everything is fifty percent off visit blinds. GALORE DOT com today. Let Him Know Adamson. You that's blinds GALORE DOT COM. Recorded live at Corolla, one studios with Adam Corolla and board certified physician and Addiction Medicine, specialist, Dr Drew Pinski. You're listening to. The Atom and Dr drew show the Agate on. The church and. Dixon. Referred Hadrian. Here's a is sad. Flaunt great somebody product to me when I was doing I think I may brought it up to you off the air. Somebody, brought it up to me when I was doing an interview with them. They're interview me actually, but You know it's just this thing that we keep kinda seeing, which is like look we gotta get rid of the statues and we got burn the flag and we gotta take a knee, the national nationalize. I love this country though man I, love this country. That's. Every single thing you say is about changing at fundamentally. So is there. A love. For. Dennis prager always says like Oh. Yeah. You love your wife dearly, but you want to fundamentally change everything about her right. The. How Much Do you love her? Yeah. Why by the way? I'll ask you why would you then love that thing. Yeah. What if there's a? There's a barbecue place that you love dearly, but you want to fundamentally change everything they do. Right. So every every flavor be changed the I love it, but right, and so the the sad conversation I was having is I grew up with this. You know this, I love this country. But what we did to the indigenous people you understand was barbarism. And Person. Just said to me. I said they prefaced everything with I. Love this country, but and then they just want in everything and the person said, they don't say I love this country anymore. They just go. Here's what we did. Yeah, and I'm like Oh. Yeah. They used to kind of pretend these kind of go. Now. Anyway, and then just show telling. You know it's like that sort of thing. Regardless I'm fair-minded is anybody else. But I'm telling you to man lane down together that ain't. Right. You know what people? Their thing. So they can kind of get away with it. We're not doing the preface anymore. Some of it I suspect is because they don't know what the country. Is really what what the foundations where they never exposed that they're exposed to the excesses and the the problems but they weren't exposed even to the original ideas and structures that you could love. Right and even what they are. Maybe, they saw Hamilton. See My My feeling is. It's simply push back for the sake of pushback. It doesn't feel like. Anything. Other than. The dog with the rope toy that's pulling one direction. You can spin around three, hundred and sixty, and they're just pulling. The, they're just Paulin here. Then even know what they're pulling on or what's gone that they just don't like whatever was. Do you think some of that is the coronavirus shutdown that they're just the reaction to that or some of TD s trump derangement. It's probably above the everything, but it's also it's kind of just. Stepping back. And Letting Twenty three year olds, who are you know sort of emotionally eleven. Just Kinda do what they will. It's literally US saying. Hey. Puppy Dog Hey. Seven month, old lab you have run out of the House is whatever make the right choice and they go. I'm going go tear up. That's so I should ever wear have running. And you go. Well, okay. But you know best I. Guess You know I. I, liked the SOFA. I'm tearing it up and I'm going to go Chua slipper and you're like, okay, why I'm not telling me what to do? Don't asleep socks. Or socks. But. I can't. You can't tell me what to do. Yeah. Right. Yeah. So that's Kinda I'm just going to do everything. That's how that's how we work. Yeah. Yeah. That's absolutely true. So I, don't. there. Is The promise is the the the the adults ceased being adult? This notion of I've told you many times as an issue. You know if you don't WanNa be the adult. Hey I'm sorry we have calls up their fellas waiting for some more to come out. Weight, waiting I am laid over not. Yeah. Let's do a little. Maybe the love boat recap. digger A lot. I watched last night to finished watch charted to yeah. The Jimmy Walker one. Know. Jay Jay Walker. Man. Julie McCoy was going to have a surprise birthday party, right? That was. Stand up for all women. You know there's a few Gloria Steinem. Says you know. In. The in this episode, there was a there was A. They had this weird thing that. Confused me when I was twelve or thirteen kind of sexually like, Julie. McCoy had the SORTA sue older good looking gentleman who is on the ship eight? You? Yeah. Oh Hi, Steve Cheese who had a great time with your last time. Yeah. I'm looking forward to this cruise. Right me too and it's like is this? Is this his boyfriend as this husband? WHO's this guy who comes on the cruise math? Love? They had avid evidently the had encounters, previous cruises and the whole cruise. He's trying to get with her at the very end when they're like seeing everyone off the boat. Julie McCoy the, cruise director with the clipboard is like making out with this guy going sorry, can have and captain stooping waiting for her to finish finish making backing out with the fucking customer like okay. Now, Julie. That the captain does he just stands there watching people in uniform making out? By the gangplank. Guy Was a travel agent. Travel. That's right. Sure that he's properly agree, and then for two cruises, he was gonNA fight it fight for himself with his. I'm looking at the IMDB here. Jimmy Jay Jay Walker, was in six episodes of the love. Played five different character. Yeah. I've seen two maybe three. One one role Marvin Jones that. Actually that's part one and part two of along episode. Different character, that's how they did is a lot of people playing different stuff on the love owed, then care they just they. They sort of have their sort of. Flavor. This is the uptight chick with the big are something. It'd be some sort of. Zone, they stayed in, but the characters were different. Yeah, they There's that. Then there was. noticed. I. Note I brought up to my wife, I was like. At the, there was a a whole African American story in this thing. And I was like look at back. Then they didn't. They didn't make up for black people. They made their their skin, look like clay, the I. It was like the makeup. It sucks that feel so bad. That's ridiculous. It's true that there was great on the White folks, they were all peach and we're now now, but you're the women, the men. looked. Fine. Because they didn't put much makeup on the women looked like clay. It was weird. Yeah. It's like unsettling got. I? Don't know if they're going for that or what? But the one woman in the African. American woman. Because Lamont from Sanford and son was Lamar. He's a player. Williams or something will or something news. He's still alive. Anyway, he was playing. Yeah. Oh, you're not doing. You're you're not doing I'm not doing my loved od Wilson. Yeah? You gotTA. Do the. LEGWORK. Everyone to find out what happened to them and where they went. Through that I find out WHO's alive? Yeah, he's seventy three. Me Just talk to him. Maybe. Yeah. I don't know I can add interesting. Will he? He'll he was in some interesting stuff and didn't Sanford. No. River Red Fox Red Fox on TV was like what? So he was the playboy on the ship and he had his assistant whose haven't. Run cover form, and then there was God, what's her name Joey from facts alive or Joe Sorry from facts alive. Turned out to be the Tomboy, Kia Kia Shouli mckean's something. McCain or something like that. Helped me am. Yeah. Yeah. Either way Yeah now, her brother was an actor to. One of those, one of those. Acting teams. Yeah Young. Young. Younger. Brother was either a year right about the same age. All right Anyway, watch la about find out what people thought of people thought in the seventies drew loves it. It's. It's an anthropological like a time capsule. It's bizarre. It's all right. Let me hit Dammar car here. Fast Easy Way to declutter your home God nothing worse. I, mean it doesn't better but come on. There's so much stuff and it's just going into landfill. All right. So let's not Let's not do that, and let's make some money by the way, not only not fill up the landfill or whatever the big island. Plastic, in the ocean, right? Yeah. In minutes, you can download macari, take picture your stuff and a description, and it's listed just like that. Once it sold macari emails, a shipping label, you stick it on the box, ship it from your home, no meet ups. No hassles over fifty million downloads and all fifty states try Macari make extra cash cell by most anything from your home using the APP, and you can get at the APP store or macari Dot Com. That's M. E. R. C., A. R., I., Macari, America's no meet up marketplace. Well, our old friend rob rate is back on the show. C., E. O. OF CHROME. It acts of talk to him before about this product, how you doing rob. How're you doing? Good. Now, I don't know if you know that rob has an lustrous careers producer movie produce TV practitioner. Not Know that until I saw his credits ers like whoo. But he but but seem, here's why go my eye goes. He has a science background from Cornell. Thought. Oh. So it's just a well trained person that just gets into interesting. Projects. Yeah, we'll tell us about the background and tell us what led you to where you are today because I think it's an interesting story. I did leave I I went to Cornell, and then I. received. An MBA, at Columbia after that, and then I went to work at Columbia pictures as sort of a financial analyst. Kinda grunt. wrote scripts broke things down to cash made presentations like strategic planning type of job. And I did that for a few years and that was an interesting time in the movie business. It was in the eighties when they were transitioning from the. Old Fashioned Hollywood way of doing business where there was some person who had their finger on the pulse of what young men wanted to see in theaters. To and more analytical approach, and I was sort of right in the in the center of that analytical approach, we broke that you've figured out the calculus of filmmaking. It used to be. I. Mean I guess every look at some point I, always want to write a book called what happens when you become the man like at some point everything I mean look at podcasting podcasting turned into a multi billion dollar business. He used to just be who what you know people sitting in there. Dan, talking to their friends with time life headset on you know. You everything in movies used to just be Weirdo renegade artists. John Derek would make a film. Look up John, Derek, if you went sort of. First off guy liked the young ladies but. Did. You ever. Do. You ever know John Derek. Bose. Husbands. Yeah. Did you ever work with him or know who he was I? have him on my Mount Rushmore of blow. Like I when I think of blowhards. I think of him I. Think of a kid stays in the picture guy. Yeah Bob Evans Love. The name Bob. Evans. GETS INC baby. Yeah. Did you know Bob Evans? Yeah I knew a little bit that was that was the curated in the in the seventies and the eighties were transitioning away from that whole idea into a more of an analytical approach, and what you used to see back then is that would be ahead of production who would last in the job for maybe two years until they had a bad hit. Now you see more longevity because there's there's more of an analytical approach to choosing the movies and figuring out what to make the Bob Evans was part of the old school, the Irving Thalberg, school of he knows better. Boy, those guys should probably be me to right into like rikers island around my dad right -solutely. Oh. My goodness. Probably. Epstein stopped. All, right. So, let's talk about the NASD and let's talk about the science behind it, and let's talk about cellular health because Drouin. I are both very much into the subject. So. There's a coenzyme, all living cells called an nicotinamide. Adnan die nuclear tied and it's an has been well known for. Probably a century. As a key metabolite, it's vital to all important metabolic functions within the cell. Like Energy Metabolism. So there's an L. inside cells called. My Andrea that are responsible for converting the nutrients from food and the oxygen from air into energy. And then that energy is transported in molecules called ATP, to the rest of the cell. In order for my the connery to function. They, need any. Indeed we have studies that show that when NASD levels are high. You not only have better functioning my country. You actually have more mighty connery. So, the salads a stronger more energized cell, but there are other processes in the cell that rely on any ideas as well like the repair functions. So when you have some a bit of DNA damage or there's inflammation, there's oxidative stress or there's an invader, an infection or a virus or something that invades the cell. There are set of enzymes called Parkinson's, but immediately go to work to repair that damage, your repel the invaders, and those tarpons on's are also in a d dependent. So when. Did any of that makes sense. Yeah. I. Mean, you can look at people look at par because parts of big story at cancer to. Department hitters out there and things like that. This is an important part of the biology as we understand it the other the other thing that's interesting, and there's so many things interesting in a d that we don't even fully understand the the impact I. Mean. They're using all kinds of situations where it works. But Sell Senescence is where I'm sort of interested in its Y, you know a daily user of of. Support. Tell us about that. The Nancy sells getting old. Like Seeing Senility Ah Oh Yeah. Before cell actually dies, it becomes a senescent cell where it sticks around, but it's really non-functioning. School of thought that thinks it's the sinise in cells that lead to a lot of age related diseases like cancer. So, there are some aging companies that have interesting approaches to dealing with anti-aging by what they're trying to do is develop drugs that eliminate sinise and sells. there's a process called apoptosis were cells, kill themselves, and then you eliminate the cells. But if you have a lot of dead cells in your body, it can actually do do some damage and manifest itself in lots of ways not just disease wise. Know physical skin. I must say, how can you test for dead cells in your body? is their way to test for that or not commercially available, not that I can think of take a look at yourself in your underpants. Thought I that will tell you. Probably help help you reach a conclusion that will. Help. Yeah. When you step out of the shower, give yourself a look. See. There's Senescence. All around you. Yeah. Bo. Derek didn't have a lot of Senescence, and there's Not when John, matter? Not. Not In Greece when she was fifteen, not not now, not so much. Right you're, you're just far too scientific. Well. I. Mean. It does kind of makes you know we. We probably overthink a lot of things you can. You don't have to measure everyone's cholesterol and their blood. Just take a look at everyone in their underpants, and you'll get a pretty good idea of how how people are hanging, right? True yes. Yes. Yes. Sir. I mean drew as a physician I. Know Jerus- texting so. That's looking at science. When someone walks into your office. You literally just look at them and you got a pretty good idea of how their overall health as well. But that comes from years and years and years of you know walking into. This is what drives me crazy by the way when people. For instance psychologists went prescribing benefits that you've never. You've never seen sick person. You wouldn't know what sick person came in. You would do with it and I feel, right. I feel the same way about people who work on their own houses. If I walk into their house I, know who's been doing. It put that crown up yourself. Interesting. It's upside down, but that's an interesting choice So I mean, ultimately, what we're talking about is the cells ability to repair itself. Is. Kind of a DNA repair system. And and I just think I pop. I worried about that. But but in terms of assisting or changing the oxidative states of the cells and improving their ability to sort of live longer and live better at that makes perfect sense to me. We've shown that as we age and Eddie levels decline very very dramatically. And idea levels decline when we're under any kind of physical physiological stress. You drink a lot. You go out Masan, you stay up, you don't get enough sleep you over eat or. You're you're fighting a disease or an infection, all of these, and virtually every disease that we associate with aging is also associated with a low level of a deep. So. It makes. It makes intuitive sense that if you elevate your energy levels, your stronger more powerful cell and better equipped to not only function whatever its primary function is that also to ward off these issues, these physiological issues. What we take your supplement, your Na. D Supplement daily. I'm a believer. So is drew Where else are we on supplements I'm going to ask both you because you both probably know them well A. Here. Provided it. It's not shaped like Wilma Flintstone. Gummy bear a good. Vinnie torch makes high-quality. Should people be on. What do people kind of need? What maybe don't they need? You know you. You hear about take this one before you go to bed not when you wake up in the morning or you know D. is important nowadays. But what you have thoughts on that rob. Of course, I have thoughts on that, I? Think. There are. Quite a bit, there's quite a bit of research on dietary supplements. and. There are some dietary supplements where the data is pretty convincing that it's worth taking. And then the vast majority, it's quite questionable. Of course. This is separate from the issue. Of whether the dietary supplement you're taking Zach actually what's represented on the label. That's a whole separate issue that we can talk about about the dietary supplement industry in general. But if you trust the brand and you trust that what's on the labels what you're taking, there's plenty of data to support the idea of taking a vitamin D or mega three, and there's an awful lot of data untrue. Nitrogen, which is our. nicotinamide driver's side, which is what we sell an all the only thing that we saw. Right. Now, as I was GONNA say. You know I, I think it's a lot like many facets of life. It's not A. It's not a black or white thing. It's like some supplements are good. Others are waste of time figure out which ones I mean. It's kind of like everything you put into your body. Think about how much you put in your body that gets labeled nutritious or natural or good for you. Whether it's a million shakes that tastes like fudge brownies that our nutrition shakes. You know what I mean, and there's my wife's got fresh pressed juices in the refrigerator that are two, hundred, fifty calories per twelve ounce container. Pure. Papaya. And Banana and stuff. So there, there's so many things that you put in your body that are under the label of nutritious or good for you or important, or whatever. It is a small percentage of those actually are as build, and your job is just fine. Those the ones that are as built, right? It's not don't take anything or take everything. It's do do your homework. There's you know there's there's two thousand protein bars out there two of them are actually good for you. So let me pile on and just say vitamin D for shore. It's hard to maintain vitamin. D, levels vitamin D has been associated with a lot of things, terms of cancer whatnot. So yes, Vitamin D. Yes. Fish Oils. They've been kind of been under attack a little bit lately. probiotics, prebiotics Bowl Cajun's for your bowels are the whole gut flora thing is a big deal. We don't know how to adjust that yet even though people will make claims, but it's clear that everyone has some more needs. rebulk more needs for maybe some probiotics. You can make a case for zinc right now in the in the face of viral outbreaks, vitamin, C, and minerals. Also things you could think about if you're young, you don't need any of this by the way by a you're under forty. But over forty, we're talking about the rest of you maybe some magnesium supplement vitamin C minerals I'm a fan of because we don't we're not. We could. We could become deficient in those watch. Our zinc can affect copper metabolism. Is the ZINC before bedtime gets causes nausea? So now, no, that's not what am I thinking of before bedtime. Mineral sorry atone magnesium saying easier. Thanks. Dr. Gary Jesus drew. All, right. Well, you can visit about and a D. Dot com and find out about this product, which is under the real deal flag and in a world where there's a lot of BS. This is the real deal rob. Thanks for checking in with us. My friend. Just want to make one thing clear inside Russia if you take an. It actually is is is not. Eligible the molecule for an idea is actually too large to penetrate the cell and it's a phosphate. You have to take a precursor to elevate NASD's in a day. So Nyah Jenner nicotinamide right beside is actually the the precursor. That true nitrogen is. and. It elevates the NASD levels about any ideas just a website that gives you information about an idiot self with, but a very good one bringing. That's why we take the supplement. Thanks rob appreciate it. We'll talk. Off The air as well. I got some projects got ideas Ou. Guys producer, yeah. Yeah. All right. We got a call up there. He before you. Let me remind everyone about our friend. Jordan, Jer. Jordan Harvard, your show we are fans we are fans of his and this episode is brought by Jordan Harbour show check it out. Especially, if you like high-quality fascinating podcast by an interesting guy interviews with heavy hitters, for instance, Cuban shows up there and one of the CO founders of Instagram, Kevin System does up for everyone you her Jordan on this show where a fan of Jordan's guys got a wildlife experience. Now, baby to right. Does he just? No matter. What you're into a professional art forger chased by the feds and the Mafia how birth control can alter the partners we pick. This is all the material you can get into an. You'll always find something useful to apply to your own life. We enjoy the show you will to search for the Jordan Harbinger show his. Name is spelled H. A. R. B. B. as in boy R. and in Nancy G. E. R. Harbinger. On Apple podcast spotify, every lift. Of Hot listen. To podcasts. Sport our friend Jordan Harbinger with the. Jordan. Harbinger. Show. Check it out. You won't be sorry you did. All right, Ken, fifty to Phoenix. Yeah Hey. I ain't going on. Hey. Do you guys understand the question? Between respirators and Regular Masks, I know they're insuring a respirator, not regular mass. I thought you. I know you would do you think the public knows the difference because I. Think we're missing the home probably not through the trees here. Yeah. Well, respirators is something. You would wear your painting in a in a paint booth there like that don't Raby and ninety five mask is an in ninety five respirator gotta check valve, and it's got four layers and it goes to so many microns you're supposed to be fitted for it and sign off on it. Work minds and industrial plants. Right. I was the minimum. About everyone else's pulling up there. Turtleneck sweater and brain right? I was GONNA say the. Not. The we we. Now at least the consensus is that it's all you need is a barrier needs to be usually to apply to to really create that barrier. Against droplets getting out into the air. Right lane differences. If you wear a respirator, your chances of actually getting, it will protect you more. To the hundreds of scale than if you just wore a cloth or something, right. A one thing that they need to say is, if you WANNA protect yourself get and ninety, five respirator amass. You'll find that. You'll find that around a little bit because the physicians in the ICU. Where in ninety five because there's lots of virus flying around, they need to protect themselves. But the primary goal of the mask is for you to protect yourself from other people. That's actually the primary goal I. Very, reverse the other person from you. Yes. Yes. Yes. And if both people are wearing the masks there by both protecting one another. Simultaneously. Yes. It all goes back to you'RE NOT GONNA. Tell me what to do. We know we know there's so to me. It's so silly to why draw the line there there. Used to so much shit draw the line at the plastic you know barriers at the bar or something but it. They did it in one, thousand, nine hundred, and what happened to the first half of this fucking pandemic when everyone was his squirting alcohol on everything and wiping everything Dan because it's not surfaced transmitted. I know what happened to that part? What happened apart ride walk in with an in-and-out bag. Would spray. Ice Appro Paul. All of my fucking bag threads out wrong. What? Yeah. What I talk? About, having to wear gloves. What about just fucking wiping the shit outta everything all the time. We couldn't figure that fucking thing out it. took us four months to figure that shit out. Yes. I had to fuck and come in and get yelled at because I was take my shoes off. See Did in China by the way guess who doesn't guess why don't listen to anybody. So it's fucking bag down. Let it sit outside for two days. Let us squirrel fuck it, and then we can bring it in a house like in take your shoes off. Close off and Burnham. What happened all the shoes and what happened all the gloves and what are the wiping down of everything I need and taking everything and distant disinfecting of everything and. Tell you the level of panic. We were in a not me that the everyone else everyone else not you? Of course me. Of course. Not You. All right. So what am I supposed to listen to? Our instincts, your your crystal brain. Thank you. Live standup tonight tomorrow, night. San. Antonio Laugh out loud. You gotta calm for all the live shows and get my book. Is. Doing stand up in life podcasts over there and you can check out. All, the movies at Chassis C. H., E. S. Y. dot com, and watch our youtube page doing stand up on it for free throw. Yeah. My Youtube page to dot com slash Dr drew also Dr Dot TV Index Dot Com. All right. So next time. Doctor. Say Mahala. Welcome the Fed Debit Twenty, twenty presented by online on your host, Bram Weinstein, we have an amazing panel guest today. You see Harold Reynolds Played Infield in Major League Baseball for a number of years. You can see him every day on the MLB. Network these days in his prestigious broadcasting career at George won the heisman trophy back in the nineteen nineties. One of the best running backs in Houston oilers, Tennessee, titans history, and Robert. Ory, is one of the most clutch basketball players in NBA. Playoff history adumbrated dipper championships with three different teams over Sixteen Years Haida all of you. Thanks for joining us today. Thanks for having me also. are, let's let's switch over to fans. Let's talk about what's at looks like what that feels like. Eddie played it Ohio states. You played at one of the most iconic legendary venue used. There is an American sport play in the NFL as well. So let's start with you here. The idea of playing football games without fans that that feels like what to you saw, I know what it feels like and it's not. It's not fun. It's. You need. The energy, the feed. All. Your your with your home and your home, you need the fans or two. When you're you're down, you're trying to figure out a hot. Worse through adversity as a team on, you need the fans support. Also you're on the road, you know opposing teams feed off that same type of energy. So the fans are very much of part of sports like anything else. They are definitely play a role in it, and that's the whole point. Is They give and say, that's why they have home field advantage. A homeport advantage home field advantage is definitely a field to which it to see. It's like like sprained practice if you will feel like any. Of were five scrimmage. Very. Much meaning out the things he's going to be a different field. Robert for you I mean for your league, they're going right into the play offs and there's no fans are what was your experience like having fans in the stands for play games and what does it mean to you to not have them in what is the biggest moment of the season for the NBA? Well. For me, I fed on bands energy in an also love going into a different like the teams arena shut him up because it was nothing more satisfying than shutting them up in having that thrill. But I think sometimes. People don't understand how much athletes we need. Fans love fans, and we appreciate him. Greatly, a lot of times we can act like we don't buy sign autographs. We really appreciate fans because they give us a energy in fourth quarter. Order. They letter. They excite us to get over that mountaintop I think about we played Portland in game seven, of Western Conference finals in Game Four for a game seven in the fourth quarter down twenty points. But we got those spans behind us. To come through and make them nervous. You know that helped us. That's why you play for Home Court advantage these moments like this when you need those fans behind you to get you over the top. So it's hard to play without fans, but I will say this without fans you go see who is the best you could see who has the heart and the mindset to get over the top because they don't have the fans the pushing a given the extra mile. So now the Chew Chew Tally people are GonNa come through at the end. I gotTa tell you though it'd be herald as a fan. That is one of the unintended consequences here of all. The things that we've always wanted to hear that we weren't sure was ever really going on. Eddie Eddie I'm curious with in football. So so much the vocabulary shared from team to team. Audible. Ottoman. Pleasant stuff like that. How will that play? It's and that's that's a great point because know the. Patriots, they got in trouble for. audibles getting their the signals knowing they're checking their getting. So that's that's GonNa. Be Interesting to the half of the crowd noise to new that out, help us and you can't pick up on things, but you can pick up like You know check with me. You know going, right? You know a wrangler in in in left the whatever it is I mean you can. You can pick up on those things. So I think the NFL in terms of game planning week to week, they're to have to change up their vocabulary to communicate what they want from plate of Lake, and it's interesting to see how that happens. Perspective, we've established you guys to some would miss the fans in their presence. But what concerns you have about people being in the stands in general. Well I think if you WANNA get through the season. Is GonNa have to be without fans, 'cause you just you can't risk fan coming down, shake somebody's hand your natural reaction by says, Hi to you. You want to reach out your hand fist pump whatever. What happens if player contacts covert through a fan? You'RE GONNA contract contact all the fans, and you're going to sell the team down I just think it's difficult enough to keep the team clean and healthy. and. Not involve fans, and I know that's not what everybody wants to hear. But I think that's where we're at right now and like I said, this is ever-evolving. Who knows by the time we get. September, it might totally be different. But I think for now is we're starting up trying to just get players on the field. I find it difficult to think they're not going to interact with fans. It's just a natural thing to do. So I think that complicates wobble. That's just my thought. Eddie, what about you? You said you fed off, the fans liked having there. With the public health, your personal health if you were playing at risk, how do you feel about the idea fans being in this thing I, think can be done I think you can find the right capacity you can. Begin to kind of. CARPAL different sections of the stadium. Every even in normal time, not every state is gonNA be fool anyway. So is only hurt market certain places. I. Think Teams at are at full capacity on the average needs to have those plans out. Think fans come come in with mask on they provide. Can sanitizers there equality? There are no. Player Fan interactions there know autographs lay all the rules out on the table I. Think it can be done appropriately i. think if you can somehow manage the concessions, you know six feet distance. Making sure people go in one way of all the time, the not all over the place. You can provide that in terms of a stadium environment that experience, it can be done a don't think the players can necessarily attract Kobe I'm not an expert. I'm not a doctor through fan in Iraq despite them being there. Is More on the Spiel des other players, they can get it well. Having fans in the stands, it can be done if it's done appropriately responsibly in has to be well thought out and they have to check the able to check the temperatures of people do a AW testing. Screening prior to that, I think it can be done. Hell you play. Would you? Probably would've singled throughout most of my career through all my career single, I didn't get married till after a baseball. So yeah, I probably would have played. I can understand guys that have the challenges though because of the fact that we look at Mike. You know his wife is expecting that I shall Nagas and I remember being spring training before the shutdown talking to Mike, and it was so ecstatic about being home and asking me what was it like in the delivery room in your kids were born and us all enthusiastic about all. That s something. You'd think about forever particularly with the first one, and so now knowing that it was gonna be an August. Prior miss a couple of games probably back. Then the pandemic hits and he's thrown into this whole decision of one is he going to do and I'll throw this at you guys real quick. But challenge for these players is not taking carry yourself. It's all your teammates, everybody's in it. So I don't know what they're doing when they leave and who they're around and everything else I. think that's what presents even more of a challenge with contact testing or if someone all of a sudden outside of your beer has had contact with somebody. Now, y'all said you gotta get quarantined and so those are the challenges and I know that's what might trotters is struggling with. So that said that long answer being single. No kids all through my career out probably played. But had I had family Robert Talking about it presents a different challenge? Robert Wood you played. If you were still playing right now. Would you play? I probably wouldn't have because you know it also depends on where I am at my career. You know if I'm like five years in ten years or like you like sixteen years at into my career, I wouldn't do it is because I know a voter. No, my wife had heart issues. I got a young kid at home. So I probably wouldn't play and plus I've made enough money that have to play so. That makes a big dip on where you are my three was established. In it's hard to say you know and plus I had seven championship. So. I'm not win another. And, it's hard to say because you love the Game You love your sport. You WanNa get out there. Show you craft it'd your crap at the best ability in it would be one of those things you have to really sit down with your family and discussed it and see what they want you to do. It will be it'll be hard, but if the me and I know, MIA, and my wife I said Noah, I'm not playing because. Of have played enough. In, my life and my family life is more important than getting some. You know playing a basketball game. Let's end on a big picture question optimistically. You're GONNA, play. All of them are GONNA chronic champion. Heraldo. Once you go lasts because baseball is such a unique position with how they're structuring their schedule and all of that stuff which year. But let's start with the NBA. Since they would be the first literally crowned champion if they can play. Is. There an Asterisk Robert, whoever wins gets thing that year At played in nine, nine, nineteen, ninety s season where you know we want to put a asked by San. Antonio Spurs season because it was a lockout. Anytime you win a championship is a great accouncement. So this should be an aspirin. A half the guys try to compete and play, but everybody's to complete and everybody has the same advantage you have I'm not one of these guys I believe in the. Asterix. Compete and you do what you're supposed to do to try to win a championship. You Win at temperature, you play hard as individual. You digit thing I. Know a lot of people I. Guarantee You if your team doesn't win it, you're GONNA say. We. So I think when you say just bad because everybody had the same opportunity to go out and compete and win the championship in. You should put yourself in position to have the best vantage possible to championship. Are A big. Thank you to our panel today Harold Reynolds. You can, of course, see on the MLB network played a number of years in the Majors Eddie Georgia heisman trophy winner course. Running backs and moral Tennessee Titans free and Robert? Owen one of the most shooter in the history of the NBA wonder of championships recommend so jealous because he's got. So much joining us today. and. Thank you us for fantastic twenty twenty brought to you by bet online.

TA John Derek NBA Eddie Eddie Julie McCoy DOT COM nicotinamide NASD Robert Bob Evans Darius Rucker Baseball cancer Jimmy Jay Jay Walker Harold Reynolds San MLB Dr Drew Saint Jude
#70 - David Sinclair, Ph.D.: How cellular reprogramming could slow our aging clock (and the latest research on NAD)

The Peter Attia Drive

2:10:14 hr | 1 year ago

#70 - David Sinclair, Ph.D.: How cellular reprogramming could slow our aging clock (and the latest research on NAD)

"<music> hey everyone welcome to the Peter Attiyah drive. I'm your host Peter Drive as a result of my hunger for optimizing performance health on jeopardy critical thinking along with a few other obsessions along the way I've spent the last several years working with some of a successful top performing individuals in the world and this podcast is my attempt to synthesize what I've learned along the way to help you live a higher quality more fulfilling life if you enjoy enjoy this podcast you can find more information on today's episode and other topics at Peter at MD DOT COM and everybody welcome to this week's episode of the drive. I'd like to take a couple of minutes to talk about why we don't run ads on this podcast and why instead we've chosen chosen to rely entirely on listener support. If you're listening to this you probably already know but the two things I care. Most about professionally are how to live longer and how to live live better. I have a complete fascination and obsession with this topic. I practice it professionally and I've seen firsthand how access to information is basically all people need. I need to make better decisions and improve the quality of their lives curing and sharing this knowledge is not easy and even before starting the podcast that became clear me the sheer volume volume of material published in this space is overwhelming. I'm fortunate to have a great team that helps me continue learning and sharing this information with you to take one example. Our show notes are in a League of their own in fact we now have a full-time person that is dedicated to producing those and the feedback has mirrored this so all of this raises is a natural question. How will we continue to fund the work necessary to support this as you probably know. The tried and true to do this is to sell ads but after a a lot of contemplation that model just doesn't feel right to me for a few reasons now. The first and most important of these is trust. I'm not sure how you can trust me if I'm telling you about something when you know being paid by the company that makes it to tell you about it. Another reason selling ads doesn't feel right to me is because I I just snow myself. I have a really hard time advocating for something that I'm not absolutely nuts for so if I don't feel that way about something. I don't know how I can talk about it. Enthusiastically so instead of selling ads I've chosen to do what a handful of others have proved can work overtime and that is to create a subscriber support model for my audience. This keeps my relationship with you both simple and honest. If you value what I'm doing you can become a member and support us at whatever level works for you in exchange he'll get benefits above and beyond what's available for free. It's that simple. It's my goal to ensure that no matter what level you choose to support us at you you will get back more than you give so for example members will receive full access to exclusive show notes including other the things that we plan to build upon these are useful beyond just podcast especially given the technical nature of many of our shows members also get exclusive have access to listen to and participate in the regular ask me anything episodes that means asking questions directly into the AMA portal and also we'll get to hear these podcasts when they come out lastly and this is something. I'm really excited about. I want my supporters to get the best deal possible on the products that I love and as I said we're not taking dollars from anyone but instead what I'd like to do is work with companies who make the products that I already love and already talk about for free and have them. Am Pass savings onto you again. The podcast will remain free to all but my hope is that many of you will find enough value in one the podcast itself and to the additional content exclusive for members to support us at a level that makes sense for you. I want to thank you for taking a moment to listen to this. If you learn from and find value in the content I produce police consider supporting us directly by signing up for monthly subscription. I guess this week is Professor Presser David Sinclair. An outlet name may sound familiar to some of you because I've already interviewed David in fact his first interview appeared podcast back in November. I believe two thousand eighteen and I wanted to bring David back on the podcast for several reasons first of all he's always interesting to speak with and we spend a Lotta time speaking off podcasts and I want to be able to share those discussions with with people second. He has a new book that is coming out in fact we have time the released this podcast to coincide with the release of that book which is tomorrow. September tenth length and third we wanted to revisit some of the ideas around an ad and our nicotinamide riboside that is and longevity these are still to this day among some of the questions. I get asked most about an even though truthfully. I don't believe this is even at the top three level most most interesting questions in longevity for whatever reason people want to know all about it and therefore I wanna tip provide a little bit more insight into that so as a bit of a refresher David's a professor in the Department of Connectix at Harvard Medical School. He's CO director for the Biological Mechanism of aging program or it's at center actually he's best known for his work and understanding standing why we age how to slow its effects we talk in the very first podcast about his role in the discovery of cer- tunes and the treatment there of let's let's see. I think you can go back and listen to his bio from that. Let's talk about what we talked about here. We talk about this idea of the information theory of aging and this is really a big part of what David's book is all about and I knew that David was going to be interviewed by a lot of people for the buck so I felt that it was probably going to be most helpful to listeners owners if I interviewed him on some of the more technical details of that book which deals with again this information theory of aging basically what is the clock that determines our aging. What does it look like an and perhaps most importantly. Can it be manipulated. There are lots of other topics that are covered in his book such as the ethics of delaying death to significant can degrees you know what would it mean to humanity we could live for you know hundreds of years. Those are very important questions. I don't touch on any of them in this interview and I suspect you'll hear a lot about that in some of the other interviews so if this the topic is of interest to you one I recommend you buy the book I really enjoyed. It and I learned a lot and that's saying something because I don't really learn a lot reading books about aging unfortunately anymore. More books are written at such a low level but that's not the case here this is this is really good. Secondly I think the discussion we have around an AB NPR feature some really up to date stuff including a couple of papers that were published in the weeks leading up to our talk and so again. I don't think this is the final word on the subject but I do think that you'll oh come away from this with an even more nuanced my appreciation for the potential benefits if there are any of supplemental agents that pose a promise of of increasing in a D so without further delay. Please enjoy my second conversation with David Sinclair there. Thanks for coming swinging by thanks for having me back congratulations first of all on the almost released book well thank you. That's an interesting time just waiting for the thing to drop September tenth. Yeah yeah well by the time people here this. It will be dropping so I kinda wanted to start with the book because I think that you last time when we were together. Maybe maybe a couple of months ago but once you start recording a podcast you end up listening to podcasts a little bit differently because now you're sort of thinking about it through the Lens of the interviewer as as well and similarly once I think you're trying to write a book all of a sudden you have much more interest in other people writing books not just for the content but the actual process and things like that so I remember we connected on this about a year ago and I won't lie. I'm kind of secretly jealous and envious. You're done yeah well. The scary thing is is you don. You're never done. Your agent says what your next book. Oh well. That's not even when I was thinking I was thinking. The bigger issue is the moment you're done. You think Oh wait. There's just one more thing I wanna say and there is that at some point the editor said no more changes David. You're done is heck of a lot of work. Anybody who's written a book real respect for those people. You're in the throes of yours right now right yeah so you had sent me your proposal like a year ago. Maybe longer definitely longer than a year ago and is probably probably a great example of how proposals books often differ quite a bit. I'm generally the book ends up being so much better so much richer because there were things in the book that weren't necessarily in the proposal so that kind of caught me off guard especially the first part of the book which is kind of what I want to talk about today. I think the second part of the book where you talk about the societal implications for for a longer lived population are interesting but I'm gonNA. Let somebody else talk about that with you. I WanNa talk about sort of the biology of this but this idea of I mean you introduce introduce a very important mathematician who wrote a paper that I remember seeing in my engineering studies paper from the nineteen forties so let's just start with that. Why is Shannon relevant to the story of aging because I certainly didn't learn anything about him. As an anti aging researcher twenty five years ago well Shannon's is one of the most respected guys in math what he did in the nineteen forties was essentially figured out how to mathematically Code Information and make sure that information gets gets the receiver. It's called the information theory of communication what led to is what the world we have around us the Internet TCP IP protocols what that has to do with aging I wrote down in the bulk it began really when I was just a postal lenny guarantees lab at MIT interesting clan Wiza- at Mit too we we discovered twelve surprise that what was controlling aging in yeast in part were these are two genes now so too in science in aging pretty famous but a lot of people don't know that the words are too in stands for gene called Sir to which in Yeast we found response to dietary restriction hate starvation and it allows us to live about thirty percent longer if you up regulated put just another copy of that gene in the e cells and make cable on WHO's now a famous MS professor. He was a graduate student who did that. Experiment put extra or two gene teased and they lived longer so that was a massive breakthrough but what Sir stands for is really retelling. It's actually being forgotten over the last twenty five years but Sir is an acronym for Silent Information Regulator Silent Information information regulator. What does that mean this gene that controls other genes it switches them on and off its main job is to keep gene silent and that allows cells to be dividing riding be healthy but what they do that is not appreciated his win. The cells stressed too much temperature a broken chromosome the protein this gene makes the surging it leaves silent regions and it goes to repair the problem fixed the problem so in the case of DNA breaks what we did was we broke the chromosome of east the sir enzyme protein leaves words should be goes to repair the DNA. When it's all fixed it comes back again to shut those sound teams down and you might see that's weird thing to do is an organism well. This is a highly conserved process. It's found in yeast cells. Just make sure the listener what you're saying you have a gene. That's being silenced silenced that then gets broken the thing that is silencing it leaves it silencing post to go and repair that which is broken only to come back in silence insights from an expression standpoint. The world outside hasn't changed that's right and the reason that I think it's set up that way that these genes that get turned on by the absence of Sir Protein help with the problem they turn on DNA repair. They hunker down. These are survival program. That's in every cell on the planet. I believe and certain enzyme that we're talking about is a master regulator of that survival circuit. So why does that have anything to do with information theory. Well what I think is going on is that this program that sat down in all souls and when he sells young a which gene should stay on in which Jane should be off gets messed up. It gets lost in the noise and what's the noise. It's this constant having to go and repair. DNA or respond to too much heat or some other imminent threat yet doing it once doesn't matter one cut to a chromosome Burkan chromosomes not gonNA kill ye sell if it's repaired but what it does over time is that cells lose their which genes should be on and off genes that should be kept off in East L. Come on one way to think about this. It very simple. Analogy is Hurricane Katrina Katrina okay so the Sir Protein of the the first responders. They rushed down to fix the problem. They do their job but what happens is most of them. Come back home. Mow The lawn pay the bills and everything's good but some of them get sucked down there. They marry someone or maybe they get lost on the way home the kind afford a ticket harm on the airplane and you do that hundred times or in our case in our lives every sells getting broken from some every day so you doing this. How many days do we live thirty thousand days. This is a problem I think over time you actually end up losing that program and L. Cells lose their identity and the hallmark of aging in yeast is the loss of sailor identity. They become sterile. They don't make dysfunctional so Claude. Shannon figured out how to preserve information you keep a repository of the original data how dressed destroyed backup and he said if the receiver of that information which which in his idea was the radio receiver of the signal in World War Two and after in our world it might be our email in aging it's L. cells in the future and we lose that program about keeping ourselves young cells themselves and what Shannon said is that they may be repository. Okay then formation if our souls a ride if they're doing a good job there should be a way to reset the system to get that complete email back again and I think I think there is one we have some early evidence from mice that we can actually find that hard drive and rinsed software so that it's pristine again and we find that we can actually improve the health quite dramatically of parts of the mouse's body now to really get into this the way you do in the book. I think we have to take a few steps back and assume for a moment that a listener doesn't know much about DNA beyond sort of the high level stuff but maybe doesn't understand what an EPI genetic modification is what things like methylation meaning how that occurs so let's go back and go through a little bit of that stuff because I think to get a firm understanding ending of this will enable the things you're GonNa talk about to make more sense so we could use a mouse. We could use a person I. It doesn't really matter for the purpose of this discussion but let's use a person because I think it resonates with a listener more more so you and I have lots of DNA. We've got somewhere between twenty and thirty thousand genes these genes are made up of lots of this coating <unk> stuff and there's coding and non coding segments of these DNA but basically it's a whole bunch of strung together nucleotides now some of them. Some are not working at a point in time right. They're sitting there but they're not actually getting turned into our innate to be turned into proteins correct. Absolutely certainly we don't WanNa turn all our jeans on because then we wouldn't have any different cell types we will just be a giant blob of cells of John <unk> probably so when you take a piece of my skin and and you take a piece of my liver when you take a piece of my eye nerve in the back of my eye. They all have the same. DNA right yeah except for your spam or your egg and some immune cell. I don't have any eggs by the way just for the record. Yeah okay I can believe us but your point is some of them are getting turned on so the DNA that are seeing in the epithelial cells of my skin are being instructed to express proteins in a certain way and that's what ends up producing skin versus the nerve in the back of my eye versus my liver etc and what's interesting is the skin and the nerve at one point were the same size when you were an embryo <hes> but the pattern when we say pattern of gene expression the way cells tone on different genes allowed notes to become knows and hopefully stay notes for most of your life but I think towards the end of your life that's the problem losing our identity and voting back to something that was more primordial. Malaika skin cell and the way the souls do that's interesting so that your DNA if you stretch it out of a cell <unk> about six meters long and they're a little proteins that wrap that length of DNA up inside of microscopic cell and it's essentially like spooling a a hose in your garden and then you pull lows spoils on top of each other so it's away of packaging something very long very very thin and tiny but it's packed up in spoil it won't be read by the cell and that's what they saw proteins to the Sir proteins actually maintain that structure of that spoil but if it's only to read the gene they removed the so proteins and out that bundle can open up and the gene can read and they're different layers of the EPA gene. There's the superficial layer where the sir proteins are and through other proteins going around tending jeans jeans on enough but there's a really deep layer. The deepest layer is what's called Dina. Myth Latian and cells can permanently for decades Mark Jean to be silent amount by putting these chemical groups called metals next to or in a gene and that tells the cell split up as tight as you can and never unless I tell you to reveal it again and that's the reason Al Brain doesn't turn into a liver one morning when we wake up now. Let's define methylation only because it's such a buzz term right now. I think everybody and their brother is reading about. Oh my God am I a bad methylated. Am I a good methylated why have an MTA far mutation dead at that at that a but let's sort of demystify all this stuff. A methyl group is a carbon group with three hydrogens on it so we're talking a very basic molecule in the broader architecture of Organic Chemistry and you're saying that when you put one of those methyl groups when you attach one of the carbons on that math all too literally a carbon on one of the ends of DNA. You have the ability to program it to not carry out. The function of expressing itself is at a safe way to say that it is this is the underlying code that tells tells us l. what type it is and has Conrad Waddington from the nineteen fifties who didn't know that there were these methyl groups what he imagined was the embryo fertilize cell is at the top of a hill and rolls down the hill and if it lands in one valley it's a nerve cell stays in the valley but if it rolled into another valley it's a skin cell and stays a skill and that's a great metaphor for how an embryo and then eventually a baby is formed out of twenty seven billion cells the baby here's made of forgotten didn't think about as much if at all was what happens after that babies born what happens eighty years later to his. Warrington landscape unscathed what happens to those valleys in those hills and what I think is happening is that we're having not just erosion of those hills so that the celtics stay where they should but they getting jostled by these. Dna a break and this reorganization of Serpentine and others so that cells start to migrate up over the Valley into other new valleys and now your neurons in your brain your nerve cells stained behavior a little bit like skin cells or liver cells and I think that's what's underlying many if not all of the aspects of aging that we eventually will succumb to and what role world as entropy play in this because when you think about these hills and valleys there's a place where things want to settle out there should be a place where things settle and stay put put but the figure you have in one of your talks which shows this projection right into the future. It starts to get blurry at the end in other words. Is it starts to look like there's more chaos in the system. Is that just the natural drive of entry within our systems. Is that the way it's expressed. I guess is what I'm asking. Ask Outright so mathematically. It appears very much like a loss of information and interaction of noise because these methyl groups that are laid down down in pristine precise fashion young there are other metals that accumulate over time in different places what appears to be randomly so it's a loss of the original pattern and that's why we talk about entropy now anyone who's familiar with the second law of the mighty namic says A. K. whiskered. We're never going to be young again because as you've lost inflammation similar to fall into a black hole never coming out or even. Let's think of more obvious examples like you can't. UN Fry an egg once proteins. Oh teens become denatured once the clear part of the egg becomes white. You don't get to make it clear again yeah or even worse. If your genome is a compact disc or DVD you scratch scratch that up and you can't read it again or even worse you break piece off that information is lost view fraud in the trash but what I think existence tells me of some evidence. Is that like Shannon suggested for the Internet or information. If you have a backup copy now going back to the genome. There seems to be something sells tells them these methyl groups the program that was laid down when you were a baby is still there and cells can access that somehow to say all these other things that have happened since you were born or since you were a teenager that's just noise. That's crap. Ignore that in fact when I tell you in my we can reprogram cells to to go young again into read the right pattern. There's a process that would just beginning to understand that says this stuff is noise. Get rid of that. Ignore that get rid of it but these other metals Foale signals these little flags on the genome. They've been there since we were babies. That's the good stuff keep that and in that way the spoils of the host the DNA in a loop that have become untangled and messed up as we've gotten older reset back to thing again so make sure I understand that if you could take the version of David Sinclair that was born and you could look at every single piece of methylation across every single stranded. DNA on every single gene gene in every single chromosome and you had a picture of that and you knew what that always looked like fast forward fifty years. Some of those methyl groups are gone on. You've lost methylation in some places and presumably in many more places there are now methyl groups added that were not present. You've had both in addition and subtraction of methyl groups groups and that now looks like a different picture. Are you suggesting that at least to the first order if you restored the methylation status to what it looked like when you were born. You'd have a younger phenotype. That's exactly what I'm saying. That wasn't like a canned question. I wasn't even asking that rhetorically because on one level that seems really complicated complicated but on one level. It actually seems kind of simple. You know what I mean. That's sort of what's weird about. What's amazing about it is that we didn't even understand how it fully works yet? We just know that there is this backup copy. Copy that we can access. At least we have early evidence of it so we have this manuscript that says that if we turn on a few key genes in the body of the mouse or in a cell it will quite literally not just act younger and turn on young patterns of genes when you measure it's age counting these methyl groups where they are it is young again and so this backup copy exists but what warps my mind it blows my mind is that there is something in the cell that we've had all along now lives that allows the cell to reset. Can I ask a question. Tell me if this is the right time to answer this question. A lot of what you're saying thing sounds like hey isn't that quote unquote a stem cell. It's very much like that because what we've done in the field is we've taken the knowledge from the reprogramming fueled which is using Oracle Yamanaka jeans and they used in the field right now by scientists by companies to take an adult cell. I could take your skill so for example grow in my lab and I could make a stem cell out of that. How does that work it strips pretty much all of the methyl groups of the Dini and that's a reset not back to being young but by being primordial by being pre embryonic in other words mutilation by definition implies an aging in some level of cell sell so technically you're most primordial cell had no methyl groups on its DNA bright bright very few and as we get older and it's not so what we've discovered as a field is again a few years ago I wouldn't have believed it is true is that this clock starts aging from conception even as we're growing in the womb how DNA inas accumulating these chemical change these metals and that extends throughout life forever and if you gave me a sample of an embryo or a baby or teenage H. girl or an eight year old I and some other labs in the world can read that DNA and by the pattern I could tell you exactly the age that sell will that tissue. It's almost like you're describing carbon dating of a cell for lack of a better word. No that's perfect. That's the best way to describe. It and I didn't realize that the fidelity was as great as you've just described it. I understood that you could look at methylation and tell the difference between a baby and a fifty year old but if I heard you correctly you're saying that if you you took a fetus at one month of development versus a newborn a full eight months later you would actually able to distinguish those on the basis of methylation taint obviously phenotype and many things would give that away we would and in fact the pace of change is very rapid and number you what is the fidelity of this when you look at one two three we four five year old is it literally that precise that it can measure the age of DNA to within a year. I don't know what the latest statistics are for for human blood sample. It was ninety five percent accurate for chronological age but we've realized is that actually changes depending on how you live your life well. It was just about to say this is not that interesting. If there's nothing you can do about it. It's just one more reminder of your birth. Certificate is relevant. If either things speeded up which we'd I'd like to know what those things are to avoid them or things can slow it down or even as you said reverse. Although that seems too good to be true right well. It's even more important than you buzzer ticket. You bus ticket perfect. Just tells you when you're born. This clock tells you how foster aging and a few labs. Steve Horvath is one of the inventors of the clock. We actually call it horvath clock. He is able to estimate not just how old you are but predict when you're going to die with high accuracy and that's really scary that we are predestined based on lifestyle up to that point. How long would you live and there are some things that slowed down. Exercise is one good thing Hillary. Restriction smoking does the opposite so right now at this moment having not take a couple of days. I am slowing my clock. You are so they're probably mechanisms. Actually we know of maidens turning on certain so your energy levels go up when you fasting and so two and do a better job of both repairing DNA and creeping more substrate now to do their job right and just like in yeast cells need to. I do both at the same time repair. DNA in key genes silent that should be silent but if we're lazy and we ilar Food and we don't exercise those programs that <unk> are designed to keep the clock from accelerating don't on his active so that's what we think is going on in. That's why if you have smoked a lot of your life or you. Don't exercise your o'clock will on average and for most people that are tested will be older than your actual age and so the only thing that you can do is either slow that down right now. We don't have a reverse in humans but in mice we're getting glimpses of how to actually literally make a cell. Hoffitz age that it once was and how does this clock work in its prediction in relative to other things that get a lot of attention such as the length of the telomeres of a cell and may be defined for the listener what telomeres ours and some people might not upi familiar out chromosomes or forty six of them are linear DNA molecules they have ends to end Z chromosome and those ends need to be protected and those ends telomeres and good analogy like the hard piece of shoestring exactly that's what an aglet is but as we get older they get chewed back and eventually become so so frayed that the cell recognizes the end of the chromosome though it would be broken piece of DNA and they shut the cell down trying to repair it and try to stick it together with another piece in he ended up with a bunch of genetic chaos one thing that sells do to prevent from becoming tumor as they shut themselves down become senescent and that's a whole other problem for the body once you go to the Zombie it's not dividing and is in panic mode telomeres. Doagh road as we get older so they've served as a critic good clock but what happens is that cells can divide foster in different tissues tissues done even divide so it's not like a universal clock like the one that I just described that Horvath discovered reserve paper that came out. Maybe six months ago. INSCI- after member the the twin astronauts one astronaut was at the space station for a year. You're the other his twin brother was on earth for the same period of time of course and the paper was interesting in that actually I'm trying to remember as one of the two papers. I read so it's possible. I am going misrepresent this because I don't have all of the data but what I remember struck me as interesting enough that I was surprised. Nobody else was talking about or if they were. I was somehow missing it was they made a big deal about the fact that a lot of changes occurred in space and certainly some of these were very obvious and predictable. You could imagine bone density going down muscle mass things like that they talked about how the resist dramatic difference in the length of the telomeres of these two twins who presumably would I assume they had measured pre and post so it wasn't but what was really interesting within something like two to three days of being back on Earth the twin that was in space had a complete reversion to what his brother was when he was back on earth and maybe I'm just skeptical but that made me a little less interested in telomeres as particularly relevant metric trick of the age of an individual. Would you interpret that differently. No I agree with that. Something that can change within days is less interesting. There's a clock compared to something that seems to be immutable and ticking every day of your life. That's the holy grail and it looks like we may have found something like that in the field horwitz's a pretty young guy yeah. He's younger than me so his his forties. I think that he's a mathematician he is. UCLA needed to be a mathematician because defined the clock. You can't just read all methyl groups groups. You actually need to train a computer that uses machine learning to find out which are the ones that change with age in those others that just randomly change. I know I've read a tiny bit about this enough to be dangerous. Chris Right so herath used the data from like alumina or something like that. There was publicly available data. He had maybe eight thousand samples to study and presumably enough of it was longitudinal in other words. He must have had some samples of the same people that would give you one piece of data but I guess if he knew the age of the persons. You could train a machine <unk> as you're saying I guess to see how much methylation is a. I guess I apologize. If this question goes beyond your love expertise on the subject sounds like he's someone I should interview as well is he able to or are you able to in your lab look at methyl groups and know if they've been there for a long period of time if they're new if they are additions or if they basically they were largely inherited. I mean do you have that capacity. We do that works because we know from building clock that at age five years page this is the pattern that was likely there for an average human and this is the pattern of an eight year old and all in between but that would be true at a macro level but I'm saying at the level all of a given gene. Are you actually able to infer that yes so Kovacs clock is built. There were a number of clocks. His latest one is built on a few hundred sites on the gene on the very specific and for reasons that he doesn't understand and I think we are beginning to understand those are the ones that are sensitive to age and take a long and some ticked differently in different tissues but he recently published a universal clock and another group at Harvard published a universal clock for mice which means it doesn't matter earth give you a blood sample or skin sample or bronze apple by looking at that precise location on the genome next to genetics and you look at three hundred of the most are they can actually say exactly what age that mouse is independent of what part of the mouse you're given. That's kind of amazing when you consider the fact that if you didn't know that a priori you had to start with all of the genes and look at all of the potential sites methylation. I grant just be unbelievable unbelievable problem when Horvath had him the other guy did this. When those papers came out it was really hard to believe because for the last fifty years we've been dreaming streaming of o'clock but evolutionary biologists said no. It's just a organisms wasting away like a car breaks down like of selection for longevity. There's no way there's GonNa be a clock because aging is not considered a genetic program and it isn't there is an program that tells us we must age no one I know in their right mind believes he's that but there are processes like describing about movement of these proteins in yeast and movement in mammals like us that leads to a predictable change on our genome that changes the way genes switched on and off as we age in very precise locations but what truly blows my mind is the cell somehow knows which are the young ones in which the old ones and when we tell it to it can reset the cell back to what it was. You don't want to go too far. Your point about stem cells is well taken. If you push it too far and some labs have done that Juan Carlos Belmonte the Celtics shoot showed you turn on this reprogramming you can actually cause tumors in a mouse or actually turn them on really fast die within two days. You can push those bowls up that landscape from the valleys far too quickly and the cells that aren't just regain their identity identity they go all the way back to being basically an embryo and that's that's not. GonNa help anybody to two days but in my lab we do what's called partial reprogramming. We push them a little bit so that they regain their youth but they don't lose their identity so we think about this for a second so when you go back to the analogy of Shannon which is is you've got receiver operator trying to communicate through a signal through an electrical signal. There's a loss of fidelity in the signal so the receiver operator pair have to be able to compare the transmitted signal to a master signal when you bring that analogy down in to our DNA. Hey is it the expectation that within every cell resides a master copy or not necessarily within every cell it appears to be within every cell because when reprogram the animal and currently went choosing to reprogram the retina restore eyesight in old mice the cells that get three programming signal from the three genes we put but in all those cells will survive will regrow will restore their function back to being young men and if a cell next door doesn't get the reprogram signal no it doesn't regenerate so it appears to be intrinsic for each cell we can also do that in the dish we can grow human cells grow nerve cells mini brain in the dish we we can reprogram those to be young again and survive a stress such as chemotherapy and Rico as other young embryonic cells again so let's talk about what this reprogramming men's. What I mean by reprogramming is that we can use technology that we use now to generate stem cells but to partially reprogrammed you program them so that they turn on the youthful pattern of genes that we once had that we know we lose question as we get older ourselves. Don't turn on the genes jeans that they once did. We know young and jeans should be on when you're young. It's which off so we lose that that's that noise genetic noise. I call it reprogramming somehow resets that pattern in terms of the hose and the spooling of the DNA what's actually going on is that genes that will once tightly bundled up by the Sir Proteins by methylated DNA tonight coming undone as we get older. This noise reprogramming somehow tells the cell that region of the genome package that up again get the so proteins to go back there. Get the method back there or remove them and get that gene to switch off again because that gene has no business being on in the retina. You might need it somewhere else and somehow somehow alytus. Ono's that that gene shouldn't be silenced. Maybe it should come on but there's a repository so in Shannon pollens. It's he calls it the observer his backup disk is called the observer in the observer keeps. A signal keeps the original signal until it's needed and if the receiver of the signal signal does the check some check some will know that every time a signal is sent. We know that it is complete because because it all methods up if that doesn't add up. That's a signal that says go. They're gonNA transmission error right and instead of going back to the original sender it goes due to the observer who keeps a copy of the original signal and gets the rest of the data so if you're sending a let's say a photo instagram often. You're in the subway way or it doesn't make it half of the pitcher will make it but instagram computers will say hey. I only half as picture didn't add up the check. Some didn't make any sense. Please resend the rest of that signal. It may be stuck in Denmark. It may be stuck in Iceland somewhere but the system set up that way and that's what I think is going on in every cell in our bodies. That information is still there. How DNA is largely intact. We haven't lost the genes too mutations that was the old idea nineteen fifties that information's that we just don't access it because the cells don't know whether to Spool up the DNA in hide it would expose it to ten on the right genes and I'm still just kind of blown away by this notion that so you can you share them wants a story about how the Horvath clock was accurate enough that you could even predict how much a person had smoked yeah. This paper recently came out they had the records of Paks per day that were accurate based on. I guess medical records and they also asked these patients. How much do you think smoking over your lifetime and they made up some number based on what their remembered the clock matched what the medical records said and and not what the person said so. I'm sure they went lying no of course not because they would have had to have told the medical record in the first place but presumably it's easier over time to tell oh like if you ask a person every year how much they're smoking. You'll get a more accurate responsive. The aggregate smoke versus at the end of that's exactly right what it tells us. Is that this clock look. There's there's no line here your DNA doesn't lie your clock records probably every good activity and repack tippety that you've had in your life you're talking about the ultimate wearable could you imagine we love our rings in our CGM's and all of these things but imagine head little horvath clock you could stick dear interstitial fluid. It's coming if you gave me your DNA. I could tell you how old you biologically. I would love to do that in fact you know. It'd be fun is let's do a longitudinal sample will sort of stress the system system a little bit so we'll do here's some. DNA and then we'll do a fast. I'll go a week without eating or something like that. Because that's a pretty extreme stress like a week fasting should do in fact we should do this with Rapamycin dosing like I'm curious as to whether the pulse Sal dosing of Rapamycin that I take does that have an impact in other words you you start to wonder are their final common pathways that so many of these higher level interventions impact. I think level is the right word the schooling of the DNA this EPI genome. There were various levels. The superficial level are these transient proteins called transcription factors that jump across jeans and tell them I'm to be read another level down of these two that we work on factually chemically modify the spoiling proteins your call him his stones and then the deepest level the third level down is is this methylation clock which is very hard to reverse as far as I know the only way to really do it is using stem cell technology this reprogramming factors Yamanaka in other words. Your belief leaf is I'm GONNA come back to that because I actually liked that level system. You just put forward but the reason you're saying that is the best year evidence suggests in the lab today today outside of using a vector actually insert new. DNA or something is you can change the rate but you can't change the direction. Is that sort of what you're seeing yeah. That's the summary of now hundreds papers on this topic. It's a scary thought all of these interventions rapamycin in eighty brewster's metformin all the date is now in of course we need to do more but the first studies said that they have relatively little impact on this very deep clock and slow it down. That's fine. They stopped the models or the bowls from jumping too far across valleys but they don't get the pulse go back into the valleys that they will once when we were young which makes sense you can't take rapamycin or eighty boost doormat format and restore vision in mouse like we ought with reprogramming factors so let's talk about that. That's obviously now. We're we're entering the future. This is talk about that experiment. Also what we did was we took three of the Yamanaka genes that they use to make stem cells and we package them into what's Colin Av at no associated bars. There's a virus by the way is already used by many companies. There are a number of products on the market. Some are used actually to fix yeah. I disease is genetic diseases so this isn't some crazy super science fiction story. This is medical. FDA approved drug development. We take take these vectors viruses repackage these three genes in which is not easy because they don't hold much so he whittled this down. We gave an on off switch which is important because you don't want to become a stem himself. You don't want your IDA develop Jim if it might we didn't know the trick which is important. which is we left off? The fourth yarmulke factor called MIC now mic is is a well-known oncogene gene causes cancer. That didn't take a genius to leave that off but what was surprisingly rewarding to see was that the mic gene was superfluous. We didn't need it to reprogram cells to be partially young again. How did you program the on off switch. Oh that's really interesting interesting to this is up in the field. We use a system where we can feed a cell or a mouse doxycycline and it's just an antibiotic so my daughter who had lyme disease will tell tell you it's not great for long term use but just for a week or a month that's fine. We've given it to mice for the Khalife. They seem to be okay. We set it up so so that what's called a doxycycline responsive gene and so now when we have the virus silence the gene doc see basically you use something inert that has a trigger bigger yet. We could've used a bunch of different chemicals but we use this one because it's you understand it well and it's pretty benign and the FDA would likely prove it because we know a lot about it. We didn't reengineer it so that was extremely tight so we don't want any leaky gene if we don't want and we also made its levels very low because they don't want to blow the system out so we made this new version of the virus and delivered it an Adenovirus for folks who might not know what the term is. These are very common. Viruses on many of us have been exposed to these already presumably we everybody has. I mean it'd be hard to not be exposed to Adenovirus at some point but unless you live in a bubble then there's so many different ones yeah and remind me that virus DNA virus or virus. I can't even remember remember I can't remember. I used to know that okay so it's a basically and how much DNA can you pack into it. I'm pretty sure it's a Dr so we packaged Gina. In there. You can pack a five point four thousand base pairs of the report for okay all right and you go back to these mice and the phenotype type of the mouse is what at this point. It's a old mouse middle aged now slowly don three crazy things to a mouse test the first thing we did was we crush the optic nerve love you took a normal mouse and you crushed it's optic nerves and now it can't see yet an only very very young mice will regrow knows he breaks by can walk again and so we thought maybe if we turn the age of those cells back to being extremely young elk grove and there's nothing that works to grow all the way back healthier did that. I want reliable punchline yet. We also these are on. Collaborations credit my collaborators again. He the Children's uh-huh Hospital in Boston and Bruce Cassandra's lab did six permanent. GonNa tell you about Glaucoma so he puts pressure in the eye pressure is one of the lodge drivers of Glaucoma and disrupts vision and then third experiment was to take just regular old mice that were two years of age and reprogram those actually they told months of Iot tweeting go too far but by twelve months of age mouse has lost a lot of its vision out interesting because that's only about thirty five year old human right. Yes forty minutes about forty year old AH those mice. We thought even that's an old house. Most People Congress oh vision in anything we have now traded much older mice and we do see some partial actual affects but okay so let me recap that so you've got the first group are young mice but they've had their optic nerve. Surgically traumatized or traumatized is through compression. You have a second group. I don't recall the age but you increase intraocular pressure to Mimic Glaucoma and then the third group you just took relatively old old mice that had a natural decline in their vision right and there are two ways that bruises lead measures vision in mice one is you expose all you show it. TV screen with moving lines and the lines can be thick or thin and you've got really good vision. You can see the thin lines and you can watch the mouse said and if it blind or conseil obviously they want now. That's partially subjective that it's not bad but don't something completely objective and you can't measure the electrical signal can in the Occidental cortex text okay so we stick an electrode in the back of the line measure the signals that come like electro-cardiogramme for the retina and that doesn't lie you won't both to agree with each other but that at one we can measure before and after treatment and there we can see what the bars is doing one thing that I haven't mentioned which your listeners may be interested in in his when do we turn on the virus and because we want to treat patients not just doing this for fun. We turned on these. Yemen genes in the bars after treatment not before because if you've got clock hormone or you've damaged optic nerve or you're old you need to be able to reverse that not just prevent the damage and so we did that so these results that we've put out there actually leashes that in all three experiments you regenerate nerves and in the case of Karma and old mice they get their vision back so let's go through actually technically how you do this so the Adenovirus vector now contains the modified stem cell basically the genes commodified stem cell is at a safe way to describe it while a better way would be these genes that specify us during emergencies so tells the cells but you took it back to you. I'm I'm trying to figure out where you so you basically have the methylated pattern of the gene that mouse would have had during development well. He thinks we've measured the clock in no cells after reprogramming and they are younger. Steve Horvath help us with that but what's also interesting is we can look at which genes are on and off and if we look at the a young mouse and the mouse and look at which genes are on and off we can say that we've got noise now genes that shouldn't be on coming on such as <hes> genes are involved in stress responses and other genes interestingly are coming on that shouldn't be in the I in a young mouse and those very interesting some of those are about eighty of them our taste receptors meaning proteins stick out of cells and smell actual taste receptors in a mouse or a Malaga's to other animals else will. They're predicted to be taste receptor of course smell receptors. They called olfactory receptors but what they're doing in the back of the eye and why they change with ageing is so far complete mystery. I could speculate that they're important for signalling chemicals. That have nothing to do with smell. Has this been identified for example in humans. Do we know that humans also have all factory nerves in there is I don't believe so. I think we're the first to figure that out but there were sporadic accounts of it because it's so weird for a few people paid attention to it but anyway the end of the stories that when reprogram the retina those genes that were coming on during aging get turned off and vice versa. How many genes are we talking about. David particular process hundreds hundreds of genes in terms of statistical significance depends where you want to draw the line so I think it might be a few hundred that are really significant but the thing that blows my my mind about this result is that the genes that went down with aging just a little bit when reprogrammed come up a little bit and those genes that went way down with aging when you reprogram him away up so it's as though the cell knows that this gene should be put back to Wales and I have some ideas but I have no evidence how that actually happens sorry to interrupt but does that correlate to how much methylation is on the gene in other words you talk talk about. This gene was down a little bit and it corrected going up a little bit. This one was down a lot and it corrected to go up. A lot is the little versus allot it correspond closely to the extent of methylation. We don't know that yet. You're right at the cutting edge of the work. In my lab one prediction would those chemical changes map map to those genes that we see change but we haven't overlap those data sets but it's a the next exciting possibility. One thing that we do see is that if we stress Stresa sell out. Let's say we break its chromosome for a day. The cell actually has these hypersensitive regions that will open up and stay open and that's evidence for EPA genetic noise and so what I think is going on is that cells in their daily response to broken. DNA and other things like UV damage when we go to the beach note with sunglasses that back and forth are we gotta go put out that fire governor that chromosome has led to these regions of the chromosome that are sensitive to uh opening up and once they're open up and metal groups of removed or being added in the wrong place. They stay that way unless we reprogram them. Somehow the cell nodes that one screwed up. Let's go back to being young again so let's play devil's advocate for a moment in clinical medicine. We're actually twenty years almost exactly to the first time someone used one of these adenovirus vectors to treat a patient wasn't it twenty years ago at Penn Jesse. I don't remember his last name now because of the GI I believe blanket on this but basically a patient died right in that sort of really really changed the trajectory of genetic engineering and I always thought that as tragic as that death was it was a little bit of a distraction from what I always took to be was a much bigger issue. which was how how penetrated? Can you get these vectors. How ubiquitous can you get these vectors. Let's use an example. If somebody had the belief that Abo e four gene I was predisposing them to Alzheimer's disease which it is right. It's a predisposition. It's not a fait accompli. The likelihood that you could engineer vector to swap swap every copy of EPO for a new copy of April he to for example seems very improbable if you're doing that once they're an adult. I mean if you're going to have a shot at doing that. As there's reports of this in China I haven't really followed this but there's all this talk about these crisper babies where they're engineering l. p. lay and things like that in embryos but and how technically difficult is this to do in a complex organism like a mouse or ultimately a human where you need had to change enough of the gene to actually put the right program in I'm blanking on what the analogy is going back to Shannon's observer observer because that looks sort of binary. It's sort of like receiver operator observer okay but here it's like don't you have to get enough of the corrected version of the gene in to actually get the optic nerve back. I don't have my question make sense by the way it is binary in the sense that if a cell doesn't get the virus it's not gonna be reprogrammed so the current limit to technology right now is also getting it into how many of the cells can actually get the virus is probably what I mean yeah at the cellular level it's binary but but it sort of analog across that's all the cells right. Yeah it is and that's the problem we face. That's why it's GonNa take a while to reprogramming entire human being these viruses like deliver for example. You don't WanNa uh you'll give yourself liver cancer just trying to reprogram your nose or whatever that wins the Darwin Award right issue the person who does that. I cured my wrinkles died side of Tortona. I would predict that at some point people are going to try and use this for cosmetic effects as well. We don't know what we can rebuild. We know we can restore retina. We can recruit wrote notes. We don't yet know how much we can reprogram an entire animal learning tire human but one thing that has held us back in my lab is that we can't deliver these these viruses to every cell in a mouse now the good news is we may not have to maybe we only need to reprogram a a quarter of them and we get to be a lot healthier and younger. We don't know that yet but in the I the reason we chose the is well. Besides the fact that we really like challenge is that the I. Has Drugs approved the viral delivery. It's relatively insensitive to the rest of the immune system so even if you've got protected yeah it's protected organ and then we've got the fact that we can deliver a lot of virus and infect about half of the optic nerves in the back of the I can. I get a vote on the next tissue to work on here prostate. You have a lot of the similar features. You have a very immune privileged location. Every single men will get prostate cancer in his life what we can't figure out which ones are going to diabet- imagine you could take the prostate gland of a man who's fifty so a fifty year old has. I don't know something like a forty percent chance of already having prostate cancer again fortunately most of those will not go on to kill but the prostate causes a lot really no need for your prostate gland once you get beyond a certain point point but rather than a radical imagine just restoring it back to a young prostate and getting rid of the cancer and getting rid of some of the hypertrophy and the other things that come along with it. I mean it just strikes makes me is a very discreet immune protected Oregon that you could go after. I'm sure there's ten problems. I haven't thought of that. A urologist is listening listening to this sort of yeah. I think it makes sense except from a business standpoint where diseases that have much more need than long-term effects so you're saying that the loss of vision is acute enough that there's there's a reason to do something about it immediately. As soon as you're experiencing visual loss exactly or you're having heart failure got no other choice but to try this or you're GONNA die. Those are the early low hanging fruit that to help people. We need to figure out. Is this safe some risk right. There's no risk free drug except the fish oil which we don't anymore. That's highly effective so there are risks and with this technology that we don't yet know what those risks are. We Gung for the I because it's not likely to cause any problem. We've gone long term studies in the mice many months no effect on anything negative. If it was perfectly safe I think the prostate would make a lot of sense if we had drug on the market and Dr could try that in clincal trial off label but I think the future looks bright right if we can get one tissue a one organ be reprogrammed so cardiac myocytes. How technically challenging will that be. Do you have a mouse model for that yet a heart failure mouse model we have. I put trophy. That's the best model we have in my lab. We may be better ones China the problem with hypertrophy as they retain contract activity right so it's sort of you almost want a mouse model where they've lost some of the contract. Hillary that strikes me as I don't know I could be wrong but that strikes me as the easiest place to try to figure this out <unk> need research. I wonder if Jackson would be one way to go <hes> interesting so what steps exist between between this proof of concept in mice to an actual human clinical trial even in phase one well. The good news is about an is studying is that you go straight to face too because you have enough other. Adna viral vectors out there that they give you your safety and phase one while my understanding is that in the I it's special condition where healthy volunteers don't want their. I injected with virus <hes> of course so you're not going to do a dose escalation blossoms. They make you do dose escalation in a diseased diseased population for example with cancer drugs a lot of times. The phase one is still done in cancer patients right well. The advice that I've been given is that we could go to a face to immediately and so the obstacle is surprisingly not getting to pay during the trial actually making virus this such a gold rush an interest in gene therapy that making these adenoviruses can take a year and it's about twice as much as it cost a couple of years ago gene therapy has gone from while so that's kind of the opposite of what you think of with Moore's law on the sort of transistor side where more interest more technology should get cheaper it will but we're in that uptake take a supply versus demand and the demand is huge and it's probably because it's the hardest thing now being able to edit the genome correct genetic diseases and now now reprogram the body. This is massively interesting area that helps huge promise and presumably Prophet. If there's promise well otherwise you're not going to get people to put the money behind it unless the very tropic the point is I think you raise the Aristo that the gene therapy used to be the prior of medical treatments because because it was thought to be dangerous risky probably won't work. That's GonNa one eighty and now if you have a gene therapy company being a few they're being sold in the billions recently. These are extremely haunt on everything. That's new breaking new ground. Investors are all over it out of the vectors today differ from the vectors twenty years ago and I don't even remember the story particularly well of when this boy died presumably he died of Sepsis or something sort of related to but not the direct proximate result of the gene therapy my understanding understanding these different types of viruses that could integrate into the genome encodes mutation that led to problems not lease with standing up a COUPLA tumors the viruses today today don't cause cancer that don't integrate and they don't have a negative side effects other than immune reaction. How is that possible that this is not putting sorry. You're saying the problem used to be that it was putting its DNA in as well as a package. DNA that it was carrying with it yeah that's my recollection that they had a propensity to integrate into the genome so whereas gene therapy today with sickle cell and some of the really obvious like if you're thinking about what's the poster child for gene therapy. It's sickle cell. It's fallacy Ziemia. It's cystic fibrosis like you can rattle off twenty diseases that are tailor-made for this because they're single known gene mutations -tations yeah. We'll people who are interested in this should Google clinical trials dot clinical trials dot. Gov has a bunch of these many many. This is a great example of how asleep at the wheel I am. It's like my day job to pay attention to medicine but yet silent into one thing that I'm interested in my knowledge of gene therapy is eighteen years old. It's kind of embarrassing myself as as I the more. I'm talking in the morning embarrassing so hard you even. I can't keep my head is spinning and this is my day job. I <hes> adorable out of this because through osmosis summit meetings and whatever but every day hey after read or at least skim fifty papers just to keep up and in my area little on someone else's so there's no way you are certainly anyone who's not falling for living can keep up so you're saying that right. Now there are active clinical trials ongoing four people with these really obvious candidate gene sickle Salaam a company. That looks really promising has clinical trials. I believe in progress so yeah. I think it won't be long. Maybe just a few years before. These diseases are correctable. Now the cost a lot and this topic we shouldn't jump into because it's a complete diversion but because they're one shots then to recoup the cost the cost. I these extremely expensive the spark therapeutic drug that treats type of retinal degeneration. It's one or two injections things injections but it's in the high hundreds of thousands per treatment. That's a lot of money in some politicians are up in arms about that so companies are getting more innovative in how this might play out and I'm aware of one biotech that said if in five years you're not cured. You don't have to pay for the treatment. It's interesting. I've also <music> heard of models sounds even more controversial where the cost of the treatment is basically taken out as future earnings of an individual visual whose health is restored so you're sort of tying it back to gain in productivity so if someone who can't see as their vision Asian restored well they're going to be able to make more money or do X Y and z more productive fashion over the remainder of their life and a portion shen of that gets paid back to Ramona rate the cost. I mean I gotta say. I am really glad that that's not the problem. I have to solve because I can really empathize with both both sides of these debates I don't it's very difficult for a drug company to sort of find the motivation to do these things without some clarity around how these things can be priced in and at the same time it seems criminal to say it's going to cost a couple hundred thousand dollars for someone who's born with sickle cell anemia to be free of sickle cell anemia. I mean Ed. I'm glad the smarter people than me. Get a fair out. I want to go back to this thing because I'm still sort of wrapping my mind around this idea of the Horvath clock to totally unrelated to thoughts. I is in the short term. Can we use this as a way to measure our progress with the interventions we have at our disposal also remember a few months ago you and me and near were sort of hanging out in Boston. I don't even remember we were doing. We were talking about some stuff but I made this argument that we already have some pretty amazing quote unquote drugs out there. There's a really obvious ones like rapamycin that are actual drugs drugs but then there are other quote unquote drugs like exercise exercises very potent drug. Fasting is a very important drug if you WANNA use that terminology loosely <unk> but we still don't really know how to dose these drugs that well and again with the case of Rapamycin. I talked a little bit about my use of it. My reading the literature says Pulse Ital- use of Rapamycin Jason probably the right way to do it. Constituent of US probably not but truthfully should be pulsed every three days every five days every seven days every ten days at what does does not really sure fasting you and I've talked about this all day. Long <hes> could come up with an infinite number of permutations and combinations for how one should fast and my fear is. We won't get really good answers in these because one the biomarkers we have today are far too crude to really tell tell you what's going on. Even slapping a continuous Glucose Monitor on twenty four seven doesn't come close to giving you this insight looking at Jeff in my opinion certainly doesn't give you this insight. We need something deeper to your point right. We need to go deeper deeper deeper and because these interventions are not essentially profitable. There's really no great incentive for the biomedical community to be studying them but yet those are some of the best interventions we have and for many of us will never have the opportunity to have an an ad. No virus shoved down our retinal cavity to is it's going to be hey. How do we eat. How do we sleep. How do we exercise is and how do we take drugs that are currently available. So do you think there's an opportunity to do this to us. These clocks to look at the extent of meth collation in EPI genetic change within our DNA to as you said even though none of these things are likely to reverse the way the intervention that you described is if we study rates have changed could be a great first order proxy right but it's still nothing to tell you within a month. What you've just done is working. If every year you're a person had a look at their clock and you could say hey David sort of making this <unk> David since I saw you last year your genetic clock clock sped up nine months relative to the twelve months of chronological aging that you've undergone keep up the good work. I can't tie it to what you've done. But would I be able to at least directionally say whatever you've done. The last year has been directionally correct versus if you showed up after the following year and it said Oh Gosh David you've aged aged two years at genetically. Something's not good yeah you might say. I got a divorce and got fired all know Gulf. It's not good but it doesn't offer much much help but andrew sort of thinking about three purely selfish reasons. I'm going to be completely transparent. I just want to know what to do. I think the clock gives us the ability to that we did it with delays but the field that it would tell film is but it wasn't as accurate as this new clock so you could do that. You could every year even every six months do your DNA methenolone horvath clock walk and have a look at your rate of change. If you could store blood samples you could go back and see what that change was back. In Time be interesting. Everybody could could save a blood sample and go back in time to are there any companies that are doing this. There are the just have sprung up. I can't remember the names of my head but you can find them on the Internet. They'll tell you deny methylation age yeah interesting. I was actually just looking at something totally unrelated to this but equally outside side of my wheelhouse the other day which was was looking at something around endogenous versus Exogenous Aga formation and I was like how has no one come up with a company to measure this because that's the crux of everything right. It's not about people get so phosphor related about how many agee's they're eating and they don't realize the endogenous production of agee's that are far bigger issue issue this like screaming commercial application well yes steve and I were approached by someone who wanted to start a company that would measure your age and then tell tell you what supplements to take and he and I didn't believe that the science was rigorous enough yet to say what would correct the clock but those experiments that you're talking about could actually do that so the second thing. I wanted to come back to on. This is something I think we may have touched on. Very briefly in our first podcast is around senescent cells and this is one of those things where are you see the picture on the front cover of science or nature and it's mind boggling. You've got this old mouse this old decrepit mouse sitting right next to what looks like August spry plump young beautiful mouse and the punchline is guess what they're the same age but in the beautiful young one we took this subset out of cells called senescent cells and we killed them so maybe explain what that is a high level and how it overlaps with is or differs from everything you've just described with respect to the methylation clock well if you just present go back to the jostling of the EPA genome in the noise. That's introduced what we've shown in my lab. Is that creating this noise and the way we do it in my lab. We like to use a broken Dini to distract the proteins. What we we see is that the early stages of aging chewed this EPA genomic noise leads to loss of sailor identity. The very end stage of that process is that the cells checkout check out all of the cell cycle. That aren't divide anymore but they don't die. They just sit there and the stuck in this emergency state. There are other things that cost senescence loss of the end the crumbs Attila's will also co sell to say. WHOA guttural problem here got a broken piece of DNA. At the end my chromosome <hes> let's shut this down before we become humor and it's thought that these cells senescent cells a really important to prevent cancer from taking off because because they shut themselves down and they stay like zombies in tissues for decades and they don't die the problem is that they don't just sit there. They're actually actually they're sort of poisoning the well. They're in stress and they're saying to these cells around them. Oh my God I'm panicked. You guys should panic too so they they send out chemicals and proteins <unk> stressed the other cells the cells now in a panic state and their EPA genome. I believe is getting disrupted accelerated as well so if I'm hearing you correctly you're saying I'm the senescent cells can be part of the cause of the methylated an EPI genetic interference with the nonsense S. and presumably dividing cell or active so yeah and so this evidence for that like I said we can disrupt genome they get those innocent souls you can output put next to normal cells and they will induce. Senescence or cancer in those old make them Schumer Genyk. We call it. The other experiment was beautiful was done by Jim Kirkland at the Mayo Clinic he took some senescent cells and implanted them a little bit in a little Dab into the cavity lining of the gut under the skin skin and those mice ended up having signs of premature aging high blood sugar and other things so little bit of citizen sells those long way and that's what's scary because because if you take fat from young and old mouse or young and old human we can actually stain them. We can cull them whether this innocent or not and when I turned we can say them blue. There's men's on they make will be decides. If you stain Kung fat it actually looks white good if you look at middle aged its pale blue and an older mouse or an old human fifty years old my age l. It's dark blue. It's packed with these themselves in the fat and want to the rest of the bodies in panic state if these fat cells and Al sending out the emergency screaming signal what is the Fina typic- identification of Jason Essence L. Well. That's still debated at conferences but we all agree that they turn blue that Beagle exercises. There are other genes that come on the signal. Soldini damage one copy sixteen Copay twenty-one these genes that courcelles check out of the cell cycle and stop cancer few lose these teams actually predisposes cancer makes sense. There were other issues which is that some cells don't have that Patel signature and there are other cells that are nonsense that do have those signatures presumably right not so many well there are some there's a mouse that was made by Ned shoplift who's now the head of the FDA so he made a mouse that would flores with firefly. Why was suffering a glowing mouse that was under the control of the P sixteen gene so that physics came on that cell. Will that tissue would glow green so we had that mouse. We've found that if a cell or tissue got stress. Let's say a mouse had an infection or it got damaged or his nibbled on or for some reason was distressed out the piece six gene. That fluorescent signal came on so you're right. There are other things that can turn this on. It's not definitive. There is actually no definitive. They've way to tell Senescence in tissue. This is non besides police dangerous engineer pretty good well going back to the third group of Maui. Is that you worked on. This was the one that was just older. Presumably at had senescent cells had senescent optic neurons cells else. They wouldn't senescent yet. I see so you'd stain those you knew that they weren't you didn't have any senescent cells that we're contributing to the visual deficits that were slowly accumulating. We looked because because I was curious as to whether we saw. I don't believe we saw some essence. The reason that it's also highly unlikely is that we don't know how to reverse an essence even with reprogram while so that's exactly that question I was Gonna ask which is if you saw them. Did they change in the presence of the reprogramming or did they still stay there. That's the next experiment actually my love. We need to know if that's true. There's there's a post doc listening to this. Who's cursing right now. 'cause I think I've rattled off a couple of next experiments for your lab Brian <hes> well. There's thirty people in my love's GonNa spend that's good again. It's when important question but what I think is going to turn out. Is that if your prese innocent and you just lost your identity then that's reversible. We you see that in the lab in the retina but if you've clicked over into this Zombie state then you're in this state that may be possibly never reversible. I suppose we'd never say never but that's a lot more difficult. So what does that mean for the future. How does that fit into your CD analogy so if you've got a scratched CD eighty and the scratches are being caused by a senescent actor. That's out of the replicating pool but is poisoning the well you're telling me you can buff out the scratches which is in the CD but you can't get rid of the scratcher and you're accumulating more and more scratchers over time you are directly should be possible to even get a senescent cell to grow. Rogan because it should have its DNA. Still there now there are issues. If its losses Tila miss it went like being brought out of Senescence or its success because it's full of mutations that can also Christmas and so there are reasons. WHY WOULDN'T WANNA get US innocence L. TO START GROWING AGAIN. You might cause cancer but there are other reasons cells checkout that isn't due to loss information so so we've got pretty badly scratched CD that we can Polish with reprogramming but if you've gouged it so deep that even reprogramming count were comed- something else probably but I wouldn't say Fisher so this is now. Let's get into sort of a little bit more of the sci-fi speculation. Where do you think would be the hi deal application for this clinically in terms of in humans explicitly for the purpose of longevity and not disease treatment so we've already talked about lots of applications gene therapy side is your belief at that is the only application that using reprogramming as an anti aging tool is a precise tool that goes after the specific anti aging phenotype. Oh look your skin is more wrinkly and more saggy eggy boom. Here's a virus <hes>. Your vision is deteriorating boom. Here's a virus <hes> your heart muscle doesn't pump his heart boom. Here's a virus versus a global little approach that says now we're GONNA go right to the master CD and somehow we can restore your methylation pattern into that of you at your birth. Which of those two paradigms do you think is sort of quasi Sifi but quasi if you had to guess predicted approach approach while I think within our lifetime you'll see the first one the Coloma patients are waiting for this. We're working on starting a clinical trial hopefully within the next eighteen months so this isn't as far away as you might think how long before we can treat other diseases. I think that it's gonNA depend on the severity of the disease. FDI but I could imagine within this decade the multiple diseases heart. Maybe not skin not enough about that but other severe disease will be titled Either One by one but we're not just waiting for that in my lab. We've already dosed mice. Yes with virus intravenously to see what would happen. The good news is also live. They're all still happy no evidence of the expression pattern <hes> well. This is the issue majorities in the liver summoned the gut. That's an ad no feature isn't it that really love the liver yeah. If somebody had got into every cell evenly we'd be set at science fiction future could be within lifetimes where we get a dose when you're young of Adenovirus. We get to age forty and we signed experience. The signs of aging are eyesight isn't as good as at night. We have to hold them in you far away. I'm there by the way I hit it man. I hit it at forty five and a half half a can't believe it. It happened overnight and it's exactly the scenario you described. It's the restaurant tiny print dark well. You're losing your vision. If you had been infected with yet Navarre's your doctor your doctor you could have gone prescribe a course of doxycycline for a month and if we're right you'll get your vision back and and you'll get who knows what back that's amazing. It's funny with all of these incredible as you describe it. This huge re uptick in the interest around gene therapy. I have to believe some of these. Companies are looking for better factors as well. I mean if the fact that I remember add no has a predisposition for deliver that tells you it's two hundred years ago as news are there other viruses viruses that appear more promising although it doesn't in academia now become with greater risk of course not these are slight variations on what's currently using that clinic and different companies using different vectors of Av nine good for muscles so companies are going for muscular dystrophy with eighty nine eleven and too good for the I. There's a menu now of dozens but they're basically also adenoviruses slight tweaks on the proteins that tell the way to go in but what I hear. Is that some companies. I forget it's Rhode <unk>. That's my recollection has made millions of different varieties and if that's true we may be able to choose any tissue. We want another words. We're not getting away from the Tissue Specific Paradigm. Well eventually we will. I know if it's on the market. What's going to stop somebody from trying this anyway because I think it gets to theoretical question question. which comes down to sort of alluded to it earlier? Why do I need a new car eventually. Can I just keep replacing each individual failing part or at some level. Do I need a new car. Is there some final thing that it becomes impossible to replace like the chassis just special year in Boston like us. Californians Californians <unk> archdiocese never rust but at some point you could replace the engine and it's not enough replace the axle place this Grandpa so if you take this organ specific approach the skin the is the heart the lungs brain. Is there something else else that ultimately is going to lead to our demise or is that effectively just the accumulation of enough senescent cells that the gouges in the C. D. becomes so deep that even an organ specific approach ultimately fails where I'm really going with. This is is there even theoretically an argument for cellular immortality galaxy. Theoretically this is as closely come to finding a way to actually live for thousands of years. I don't know about mortality. I think the the problem with what what I'm calling the information theory of aging which what I wrote about in my book is that we do lose information. Every cell does experience mutations. It's not perfect though I know I can take some of your cells and clone you make a young version of Peter but it doesn't work for all cells and so ultimately your thousand years old you may have lost a lot of the genetic information but EPA genetic information because there's this backup drive this observer that we have found existence holes somehow that you can tap into as long as the genome the DNA strands is still largely intact we can reverse ageing but it's an information loss issue so the gouging that we get may scratch some of the foil in the CD of the Devi and you lose a little bit of the song which you'll never get get back now that said if I was George Church using my apartment he would say no big deal by the time thousand goes by we can replace anything and that's probably true her whole system regard bonds across whole newhart put it in. That's going to be doable so what I think. The future hold is following a lifestyle where you're monitoring. Bring yourself with devices vices. Tell you what to eat when to eight. If you WANNA pay attention you'd have to listen but when there's a problem notified you've got a tumor somewhere in your body. We've detected detected. Joe Had that killed before it grows. That's going to be twenty years ahead of what we can do now for patients. That'll keep you young healthy for a lot longer in the meantime. We'll learn thanks to guys like you and clinical trials what to do to live longer whether it's the perfect excise the perfect combination of Diet but but is that necessary. I mean if you really stop to think about it. Couldn't you just make the case that all of this nonsense that people like me do all of this ridiculous effort that goes into the fasting and rapamycin and this exercise and sleeping and all of this fun killing activity of my existence. If I could reprogram program why would I do any of this and who can argue with that. I mean like I could literally go and get a most beautiful pizza burger imaginable right now and not worry about any of this stuff right. That's if it comes through so so far so good if you can restore vision. I'm sure you can restore a lot of positive body. Let's it's a reprogramming doesn't work that well and you say you get senescent cells your organs eventually. Luther information in gene. Then what will you can delete themselves. You can take someone else's organs or grow your own in the dish rather pigro. You're on with all that put down. If that all worked. I would challenge anybody nobody to say that that wouldn't allow people to live a lot longer. There's still people out there who say we never gonNA make it cost on average eighty five little on two hundred London hundred twenty well. I don't know I think it's much easier to imagine an upward movement two hundred for example. I mean look that's sort of my point of view right. I think genetically engineered to stick around till I'm in my early to mid eighties again. This is just looking at my parents which once you get over eighty your genes become a far bigger predictor of your longevity than in your sixties virtually uncoupled. I feel like I've got a great road map on what it means to get to be a hundred which is still so casting. There's no guarantees but it's like how would you stack the odds in your favor kind of thing but it's an entirely another animal to imagine a world where you can take individuals and even get them to be two hundred. That's a really big leap and I would have said three years ago. It's impossible. What did you think three years ago would have been the Lumet's of our technology and that's again three years ago. You were thinking I could give you more N D. I could give you more certain things to activate adventures or two wins. I could tweak your Mitochondria. This waivers is that way based on that level of manipulation. What are the limits. You thought we were so my thinking was having come. Come from calorie restriction world that animals that are restricted live at best thirty percent longer and they healthy which is great embassy are medics rapamycin rapamycin metformin. They can depending on how sick the animal is but let's say even Rapa in a non sick mouse can give you thirty percent more life right so as long as we are the mouse we could live three so no thirty percent of eighty two big deal that gets you through one hundred. That's one hundred that's why I thought someone who who does all these. Things has a better chance of reaching one hundred than ever before but what I didn't take into account in those numbers. Most people don't when they think about this if we make it to one hundred okay so that means I'm still alive in the year two thousand and sixty nine. What technologies do they have. In two thousand sixty nine. He's reprogramming and common thing probably will be yeah so in other words. This is the optionality play. It's if you add twenty years of life extending getting someone from eighty to a hundred you have to take into account the probability that things come online during that period of time that can also impact very variable that you're trying tend to manipulate yeah and already every month that we stay alive. We get an extra week of life. That's how technology is gone. Currently wait say that again extra month distance. You'll l. to live the next week. Come on that seems too good to be true. That's a twenty five percent plus up a campy right. I'll check on it that I hear you right. tweet that out if it's right but that's what I recall call here. I'm only questioning it just based on. It seems too good to be true. Every additional months of life is offering a week of additional life extension just based on the technologies analogies associated with I mean 'cause there's no evidence of that to date is there because we really have seen a compression of life expectancy over the last two years. Haven't we actually seen so up until I think I don't want. I'm probably misquoting this but directionally. I think this is right up until about twenty fifteen. Life expectancy was increasing acing <unk> at about point four percent per year. That's now crested. I don't believe that in this environment that we live in I in other words we have figured out a way okay to eat stress and not exercise our way out of all of the technological benefits that have come our way and that's I think why you're seeing this sort of cresting right where we've solved all of the infectious problems that gave us most of our longevity gains way back in the day we figured out that you shouldn't drink kind of your sewer and we learn to wash our hands and we've got great antibiotics but these chronic diseases that are killing us now the force that's driving them which I think think is basically food sleep lack of exercise stress Etcetera Etcetera. I feel those things are weighing down on us more than modern medicine is giving us tools to fight-back and at the very least they're at a standoff suddenly in the US that's true it's not true for all countries that one week to a month thing might be anonymous stat than Oh yeah. It's a global increase increase in the maximum lifespan so that might take into account again. I don't follow this research closely enough to say it but it might be that well. You're getting more vaccines in the hands of people who are otherwise unvaccinated and getting fresh water and food and to people who otherwise don't have it is that you think it's not no have to correct what I said because it's very important it's a graph of the average lifespan of the longest lived country at the time so Japan has been leading that full lost decade or so so that's important means average life span is increasing at the top end so if country uses all new technology and has good healthcare and people don't eight themselves to death or take opioids that continues to March up what doesn't seem to change change in fact if anything has plateaued or reversed is the maximum lifespan of humans which if you believe jungle men she was hundred twenty two people will debate that but some people have made it seventeen hundred and eighty no question about it but that seems to be current limit but did those people take themselves absolutely not no. They're the opposite nearest nearest done great work on that topic they smoke and drink themselves to an untimely at one hundred seventeen but what if they had access to the knowledge that we have now which is lifestyle some of these medicines that we can help. Maybe they would help those people to get beyond that but to really go beyond that I think you need something really a new and that's why I'm a lot more optimistic than I was having seen what reprogramming has in terms of potential to be able to not just slow the clock down which he's inexorable seemingly inexorable but actually get cells to go back in time well. I mean it's interesting. I could talk about this for a lot longer. I think at this point I mean I think the readers will enjoy your book greatly of deliberately avoided asking. You I think some of the questions that are also on my mind about what are the implications of this. I think I get asked these questions a lot and I just defer just punt. I just say look. I'm not even trying to solve a societal issue. I'm interested in the longevity of the individual Israel and that's a hard enough problem so that's kind of the one that I want to think about and put all of my energy into but in your book you really do actually try to ask the broader question which is what is the implication of a society where people can live to two hundred it would change a lot of things so I'll let the readers either here you on other podcasts to talk about that or I do even better in just actually read the book themselves but I want to kind of come back to some things that we touched on really briefly in our first discussion that I've had so many follow up questions nations on men so if you still got a little enough to go back to Boston tonight so let's talk a little bit about your own personal habits around stuff so let's let's start with metformin. We've talked a little bit about metformin there couple of papers that have come out recently that have suggested a may be met for men in the the metabolic metabolic healthy person and or the prisoners exercising is either not effective or potentially blunt in the effects of that. How are you reading those papers. Well thought what you wrote. Online was excellent. I think about the same way. Which is we've known that one of Mitt Foreman's main effect is to quote unquote poison mighty carded inhibitor a group of proteins that generates energy energy in Monaco Andrea and the response of the body when it has a bit of inhibition of this is to say well. I'm low on energy. Let's build up those factory. Semitic Andrea are often called the packs of the battery packs of the cell. They generate chemical energy. If you're young or you exercise or your calories right you'll have more greater area area of these Mitochondria so more is better in general for humans while Mike Connors as we get older we lose that ability metformin slightly inhibits that activity liberty and the responses to make more of them problem is that if you're constantly inhibiting those mitochondria that's not going to be seemingly helpful with this new study study for building up my country after exercise now you could argue that. Maybe don't need to have more modern concrete after exercise but I think he probably would benefit from Alexandra so what you suggested that I think makes a lot of sense though we need to prove this or at least test it is that if you're exercising don't take my former on the days we do intense excess the next day after to let your body recover and build up my camera. This leads to something I think is a very clear theme in in all the work that I've done the work that others doing and what you've been talking about. which is pulse your biological stress? Put your body in a state of anxiety or fear. The're adversity but you don't WanNa do it. All the time. You body needs chance to recover. If you WANNA take a supplement. Maybe don't take it every day and with rapamycin you don't want that on all the time in fact. I wouldn't take rapamycin suddenly foes exercising because it's gonNa tell us L. Hunker down and not grow and you may not even he'll after exercise as well with truck Muslim so I think that the view that the combination of hunker down fast but then exercise on alternative days take the supplement the next size untold until it tended day. They make a lot of sense. Do you think anybody's going to be able to probe this. I mean near as working on getting tamed funded and that's obviously asking a slightly different question. That's really going after a non diabetic population but is it going to be able to look at this. Do you think it will be able to tease out this this issue that we're talking about or does the study not going to be structured to be able to answer this question. I've not heard of anybody WHO's testing directly. Usually there's just one variable. It has change the way you take metformin it has but I need to put a caveat is that I don't take metformin regularly anyway. I need to find the right time to take it and before I was taking when my stomach felt in good shape and you can tell when your stomach feels out of wacky. You've eaten a big meal the night before or you're just not feeling right a little bit heartburn under those cases. I don't take sigma forming because it does a number on my stomach which is great if you don't want to eat but also I'd prefer not toys have a sore stomach so I was already timing it so now. I just just take metformin when I know I'm going on a long trip and I'm not going to exercise on planes and trains. That's a good time to rebuild your body and then if I'm at home and I'm exercising sizing a couple of times a week layoff foreman and then what about rapamycin have you ever revisited that I did take it just as an experiment but haven't taken it breaks Braley one of the things I do when I'm fasting as I'm not taking those things obviously so any period of fasting longer than a day. Those things get stopped again. That's sort of an idea. That's not sort of supported necessarily by evidence one way or the other when we last spoke you were taking Rivera. Trou- aw you noted that you were taking it with sort of a fattier meal. Is that still something you're doing. The evidence of residual continues to be good and suddenly does no harm. I do take it with my tiny bit of Yoga in the morning which I make myself grow yoga at home. I missed that that does no harm. I don't have any negative effect. ACT MOCATTA vessel system seems great so do you think that reservoir trawl like. Where do you think ranks instituion activators. There's others on the market out there. There's other supplements supplements even like terrace still being that are sold that you can buy online you very eloquently described the story if people haven't listened to our first podcast obviously there's a great opportunity to hit pause. Go back and listen to it because you talk about sort of the novelty of risk fair trial and how it was the first sort of built for purpose custom. This is what what it should look like. Oh let's go get it but it's been over ten years hasn't it was not like two thousand sixty thousand seven. We first showed that it activates the time sort wants to an in yeast and extend attend last night. That was two thousand branch easier so do you still think revert. Paul is the best if because this is something I haven't done yet. I just haven't been able to convince myself that. It's just just one more thing. I need to add to my already complicated regimen and if I wanted to start taking activators. Would you recommend referral. If so what does her would you recommend I take something different and again you can speak speak to me and you don't have to give advice anybody else yeah. I never give recommendations but I continue to take virtual because it's cheap. It's harmless as far as we know but the evidence keep stacking up. The long term is beneficial. I mean it's not going to cure. Diabetes is not as powerful in human studies or in mice as rapamycin question <unk> but does it extend the lifespan of a mouse. That's eating a western diet absolutely adults. That's been done many times. It almost seems like it falls potentially into the metformin trapped which is the metformin data in metabolic -ly unhealthy people. It's pretty hard to argue that metformin beneficial paradoxically the people who are most obsessed with this stuff are are already doing so many of the other quote unquote good lifestyle things that it you wonder. Is it possible that you're already doing such a good job of all the other things you manage with respect your health. The spirit trolleys neutral will maybe if you're optimized like you are. I think as good as it can get but if you're elderly and you're not exercising wheelchair. What else are you GONNA do. There is some data in my lab that I'll share with you. We haven't published yet but I think it's interesting to mention and I presented it at a meeting in Rotterdam last week for the first time to a big audience. Let me just tell the audience quickly. What residual is it's plant molecule? Get it from red wine in very small quantities but the amount that we're giving the mice and humans Saudis. It's it's hundreds of times more than that. So three can't drink your way into enough respect a troll no glass of wine but that hasn't stopped people from trying right the molecule. I take a grammar virtual in the mornings high does seem to be fine what did the ATP study way back in the day as a human equivalent or is it too difficult to make normalization so it p showed healthy mouths on a lean diet. It doesn't extend sorry yeah and then in your lab you took obese or unhealthy mouths on crappy diet. Extended lifespan depends what you start. The Diet was extensive was twenty thirty percent can on how you count and the dose roughly was what we did. Two different doses. They both worked on was twenty four weeks. Kick Nylon was two hundred and forty makes pig too big difference. That's a tax difference yeah right and the low dose was was just as effective or do the log higher dose do that. The lower dose didn't it kept mice from gaining weight all right so you're closer to the twenty four megs per gig no. I guess you're taking a gram yeah. You're sort of in between those right yeah. It's on the high end but the result is the following. We had a science paper published in two thousand thirteen where we went to the effort sort of making a finding we searched for mutation in the sort one gene that we had published his likely the waivers virtual works and that mutation blocked trolls ability to activate the ser- to enhance and that's being heavily debated and highly controversial. Russia is one of the big controversies in my career so we were forced if not encouraged to do better to went back found this mutation that blocked the activation of this enzyme and if we're right then virtual won't work if you've got this mutation in a cell and we found that was true the drugs that were in development the super potent ones also blocked apply this one mutation what the mutation did was it made an enzyme that couldn't be moved it had a stiff elbow and without the bending of the protein at the elbow virtual could activate it anymore anymore and we know this very clearly it's being well published and cited but he's big experiment and being ten years in the making you take the mutation you put into a mouse not just to sell a mouse that takes a couple of years because a couple of years and now we have a mouse that isn't normal. It's missing one amino acid in an enzyme that renders it susceptible to refer trawl. Wuss calcitrate its immune to the effects of reversal in the test you and now we could repeat out the two thousand six study of the high fat diet within without reversal and with and without this mutation and I didn't know this was going to work in fact it in the history of pharmacology. I don't know if anyone's ever found one amino acid changed. The blocks plant molecule in the Diet is very difficult because the Diet these molecules implants hitting probably hundreds is a protein but we made one change now we could ask the question definitively if you give a mouse was virtual which benefits still occur year what he retenue it but also so which are off target which are working through something else that's just as interesting and I really don't give a damn anymore about what the answer is. I just wondering and so we did express the student pretty much definitively would like to hear anybody who can disagree with this statement that <unk> extend lifespan by activating at one and it begs the question. Can we apply that to ourselves which is during those periods of time when we are not fully dialed in. Would we benefit from from respiratory all well. That's the reason I'm taking virtual is. I don't actually hall sit as well. No unfortunately you caught me out. I'd like to take it every morning. I found that it's been good to me. Health great doing fine. It's one of the longest experiments have done for the longest but it's ongoing and because I'm changing other things all all the time to see what works. What doesn't I've kept that constant so I'd love to chat about. Him Got a little bit more time here if you're willing is I still probably get more more questions about nicotinamide riboside than and NASD's specifically than almost any other molecule that sort of out there we talked about. I'm writing a book now and part of that book. There's an appendix in it in the appendix what I'm doing is writing a short section on sort of the drugs supplements mints and Hormones that I think are most interesting and so I'm including of course something on NASD and and our I think I've identified seventeen or nineteen drugs supplements implement hormones that I want to address in this appendix. I would say that I get more questions about an R. and D. than all other eighteen put together. Maybe with the exception of Metformin so this is a topic that just continues to interest people I would say that my understanding of it sort of six out of ten level which is enough to be dangerous dangerous and enough to be frustrated at the fact that it's not nine out of ten level and we talked about this again the first time we spoke but let's go back for moment explain. Why do people even care about any idea. Why should one care about energy levels while I've talked a lot about sir tunes today's the protectors of the genome and the EPA genome. They lose their activity the over time they have to things that require activity for maximum activity we mentioned raise virtual which is activated you can eat or taking a supplement. That's the accelerator pedal on this enzyme family the few all that they also need one hundred percent without it. They don't work is eighty and eighty s a molecule. That's in our bodies. We require it every second of every day to exist our bodies use it for chemical reactions and without everything shuts down and we're always making more and we recycling it all the time. We have many grams of in our body. It's probably one of the top two molecules that's important for life and one of earliest that have ever evolved on the planet the other ones. ATP which is Chemical Energy and it is also used to be the most boring molecule in biology he just had to learn by rote how was used by the body and recycled nickeled and we just a bunch of chemical reactions and it was forgotten about during the nineteen sixties seventies and eighties in the nineteen nineties especially in the two thousands was discovered that it it also acts as the buddies signaling molecule and we think tells the body when you're exercised when you're hungry and is largely how calorie restriction works so so we think that in organisms like worms flies yeast more attias better when you give them on eighty they live longer and the question is is that true for humans as well and the idea dear is that by either replacing lost any D. or boosting it to levels that you would only get if you run marathons constantly you can turn on tune defenses and and other aspects like DNA repair proteins that need an eighty so again we could almost be back in the paradigm that we potentially are with metformin and with resveratrol. Verret trawl with is it might be that the less healthy you are. The more you could benefit from supplementation or restoration correct I believe that because so now animal studies and other studies the people on the benefits of any and of reservatrol of seen predominantly in mice and humans that are a beast or have a disease and so they replenish what's lost. That's it if you boost the levels in mouse of any we published a few years ago uh actually no it was a year ago that raising them above normal levels in an old animal gets you back to having a young. INVESCO system and they can run just as far as the mouse but when he gave in a d boosters to the young mice they didn't run further but they did if we exercise them and gave them restrict same time so it was the <hes> fuel but not the trigger still needed to actually it wasn't enough to get the expression basically of the behavior in a three month per young males but in a fifty year old I would say that at least speaking for myself. I already have some deficits. I'm not as perfect or as healthy as I used to be and so that may actually help more than before all right so let's talk about boosting it so the first question is David can I just go out and buy an ad in a pill and take it. I I think they will sell any ideas appeal. Let me reframe that. Is there a biological rationale for taking an orally very few people you start taking any early what we've studied in humans any mice extensively league knows extensively as many would like is getting precursors to entities because most people take any. D- intravenously that's sort of the typical way it's administered in this country or elsewhere right right but as this adage and there's some evidence that N. in eighty doesn't directly get into cells. It's a large molecule is some evidence that nerve cells. Take it up but in general it has to be broken down first before taken up into cells and reconstitute inside the cell that may work fine. I've heard anecdotes that I've e. N. D. is interesting interesting results other. You could argue that the placebo effect coupled with the actual physiologic responses one might have to nicotinamide could explain the quote unquote reactions actions in the feelings that people have intravenous. Ad But is it safe to say that the at this point in time our scientific understanding is that intravenous an is not not sufficiently making it into cells and more importantly might have Andrea is at a safe solution. Will it gets into my country because at least if you believe this literature there's an innate transporter that pulls it into my country but not from the plasma right. That's how I I haven't seen convincing evidence yet now I haven't I haven't read every paper on the planet but I'm unaware of what you haven't read every paper in the planet. I mean you don't come on this show without reading every paper on the planet. Well also my kids. The AD needs a lot more clinical research agree with you that I'm a little skeptical on that. Okay so then you said okay well we've got this idea taken orally take something like nicotinamide right beside and I can go by this Amazon today yet again so NPR for short. We're GONNA talk a lot about abbreviation so nr DR becomes an A. D. How right so. NRA's nicotinamide rive aside. It looks actually chemically similar to how DNA is made interestingly. It's what the riboside right beside means nicotinamide vitamin B. Three so it's partly vitamin B. Three partly a piece of DNA so that is a molecule that sells suck up through a transporter well understood they stick on phosphate it becomes an amend nicotinamide monitoring nuclear tied and then the cells turn that into an eighty so it's two steps and are into cells to two eighty and then once it's into any D- it's then N. recycled. It's turned into nicotinamide want us to react with it. Micatin might is abbreviated and am typically and that's a version of niacin vitamin around three but maybe the loss can. I just take high dose of Vitamin B. Three and that there's some interesting things you can raise eighty by just taking a N B three but you're missing out on the other components that the cell now estimate which is the right beside sugar DNA park and the phosphate so it's not surprising that ellipse showing that your goal is to raise a in the body at least in a mouse. That's been studied that Niacin isn't as effective as taking in our ornament and there's actually reasons listens to avoid taking high doses of nicotinamide unless you're a cancer patient where it may help but nicotinamide we showed back in two thousand and two is a really effective inhibitor of of the search engines which are enzymes that you wanna keep on the whole point of raising a and so we try to avoid Timo while raising ad and actually I hadn't thought of this but it would be very useful if the field had a definition which is the ratio of in eighty two nicotine one because that would give us an indication of the boosting the gas to <unk> engine versus the break yeah so right after you and I spoke last year. There is a paper that came out from Princeton Josh Rabinowitz his lab. They looked at oral nicotinamide right beside it was a tracer study that looked at mice where they gave them. Oral are and basically the question was what is the fate of this. Where is it going. What that paper showed was? The liver took because this was an oral of course oh that stuff gets the NRA gets absorbed out of the gut presumably and very quickly everything in the gut makes its way to deliver. I and it's called the first pass effect and it was in the liver that most of that and our it turned into an A. D. but the study didn't find that much and are made it out of the liver in fact what the study if I recall an now oh it's been so long since I look at it but I think that they saw an. AM nicotinamide was up in the blood but not nicotinamide riboside which you presumably will still wanted some of that leaving deliver to go to get into other cells because I'm assuming that you don't just need more energy in the liver correct. Wouldn't you want it. Also in the muscles or other cells will yeah you would but it was a new study that came out that showed that if you give an are two people in a clinical trial they could get an eighty levels raised in muscle title as well which said it would this one was just was posted on by Walk Yep Yeah. This is the one that hasn't been peer reviewed yet correct and it also showed the very high nicotinamide levels in the blood yeah yep right and so I think where the field is now is trying to get the deals high without okay yeah. That's a study that was using a very high dose are correct. This is a thousand milligrams right Yep. Okay okay so that's taking on somewhat four times the posted dose that's given when you buy the supplement's online yeah. It was a good study placebo control the had average. BMI was slightly lightly higher think it was in the high twenties. Every age was a think up in the mid fifteenth. There was a higher age group where you'd expect some effects so they proved at least what we seen in mice that you can get an to rise beyond the liberal. How do you reconcile that if that study demonstrated that there was an increase in NA D. in the muscle muscle. How did it get there. It couldn't have got there from the liver. The liver can't to my knowledge can't export. NASD to the plasma to the muscle. Does that imply I that the dose potentially in the Rabinowitz study was not high enough for enough excess in our to leave the liver to make its way to the cells. Does it suggest as at least one author has suggested potentially there was a methodological error in the Rabinowitz study where through who freezing the samples some of the are was not detectable thawing something by the way. I've asked people on both sides of this and I'm getting conflicting inputs on this by the way <hes>. It's very difficult to sort of understand this again. I don't think people are bad actors here. I think it's complicated stuff and the essay's don't don't lend themselves to necessarily working out every time but what is your best explanation for how the thousand milligrams of oral in humans made its way into increasing zing muscle and a de Paul. It's getting poss- deliver the NRA is getting past the liver well. That's the simplest explanation you've got to start waving and saying oh well. Leva then sends out an enzyme a signal of think that possible but they didn't look in the Mitochondria. We don't have the entity made it into the Mitochondria correct they didn't they didn't but there a couple of recent studies that show that it's very important for the add go up in my country at particularly. Yes and I don't think that's been demonstrated hasn't at least not inza healthy. We're GONNA come back to the other studying moment. If I recall that steady you're talking about showed a few improvements in certain inflammatory markers. Is that correct right. There wasn't much change within our it was on its mental nation nation went down in the muscle and if anything might drill marcus activity will lower wor lower that was something that didn't make a lot of sense although you could argue if the Mitochondria became more efficient. Perhaps he needed less activity but you start to wonder if that becomes hand waving as well. What's your interpretation of that particular finding finding. I don't have a good explanation other than that's what happened and that's what we'll see with other studies. I think we just need to check if all the precursors do that because we don't know if it's a in our our specific effect or if the whole class of molecules will do that as well that'll be interesting to see but what I can say that it's a surprise because Johan Orix who's over in Switzerland and myself and Matt Cable Line even who's shown in Micahel disease that anime and some cases and ours well does boost mighty conductivity collectively these a mice and it may be unfortunate that humans are just not mice and that's where it ends. I don't expect that is not true but the data won't lie will the clinical trials all we blinded. We got many trials to go but there are differences between men and are so curious to see if in amend has the same effect in humans as well though studies are ongoing. We don't have any good data just yet and do you think that Annan would be best administered through a regular oral route or would you you WanNa do it through an S. L. Route. Somehow bypass the liver. Do you think that there are opportunities there with either are or any men to get even higher plasma asthma concentrations but without this compensatory rise in nicotinamide potentially as harmful while the S. l. route. I'm asked about a lot sub lingual. Put under your tongue. Try and get taken up by that and let me explain why this is the case because it might not be obvious if you're listening because you might be saying why would putting it under your tongue be okay but swallowing not and the reason is when a person and swallows the medication it goes through from the stomach into the June him in the Elliott usually in June which is the first part of the gut after the stomach it gets absorbed orb and that blood supply goes straight to the Lavar through this thing called the Porto circulation and so most drugs actually have to be designed with that in mind either immune to delivers metabolism or designed such that there pro drugs in the liver actually turns them into the right drug. When you're talking about putting something under your tongue just like someone who for example carries around Nitroglycerine if they run the risk of getting chest pain that drug gets directly absorbed into into circulation and doesn't go through the liver so they just explained that for the listener to make sure they understand why that would be a potential advantage and also there's the complicating weighting factor that a micro bio will love to chew up that are probably and as an increasing studies showing that microbiome does eat up some of the molecules that were ingesting ingesting so that Niacin part of the molecule nicotinamide it comes off pretty quickly. Even if a molecule in your fridge gets wet you will start to lose was that nicotine might bond that'll break off and in the God some evidence that people have published in some haven't points to the gut playing a major role and Dan how much this actually gets into the body and how typically the public and not doing this for a living they don't see the brutal struggle for academic survival level going on but now in the days of put cost like yours. Peter the public can actually see this play out now. That's good because public can see what is the cutting edge of science and make their own decisions and here expert's opinion but it's bad because it makes it look like sciences on giant food fight but that's normal and he knew field will have these disagreements agreements about is your essay. Working is transported taking it up is microbiome destroying it. Do we need pro-drugs for the liberal. Just put in a man onto the tongue and we we don't have any really good answers. I'm afraid to say that right now but I can tell you what I see emerging happy to give my opinion. These are not effect. These are opinions and I think we're all entitled to our own opinions selling not facts. My opinion is that the microbiome removes a lot of the NICOTINAMIDE ferment amendment and of inner before it's taken up by the gun there are some studies that I've seen and yet available that traced movement of the molecules through an animal. We don't do those in humans typically because they're very expensive you need to have Eissa topically labeled molecules labeling different parts of the molecule but then you can say okay where did the nicotinamide though with the sugar and so I've seen some day now. It's not all in agreement but if I was to summarize it I think there's a little truth in everybody's results. I think think truth that it makes sense not to put it all through the gut. It makes sense that if you would have a lot in the gut that's also going to work some of it will get through the some truth in that amends broken down in the Gut and then taken up by the gut and remade in the body into an ad because you basically just pulling pulling apart a three piece Lego set putting it through the screener and then reassembling it on the other side that seems to happen too but also I've seen day on that looks it's convincing that some men and some in our gets straight into the body goes to deliver some goes beyond the liver into the muscle and so it's messy and probably Never GonNa be one single answer to what's going on in the body with something this complicated but his view it is that suddenly for the members of the public. I don't think they care if this transporter. They don't care what we want to disagree about mass spectrometry essay for in a man. We'll figure that out that'll come out in the wash. What's important is does it work in human. That's really all we know what these molecules do amazing things in mice to health and in some cases to longevity the potentially actually the most important study of this is not yet out yet which is this. It P for an are in mice correct that should be the most robust analysis of should not in mice. It is so they use mixed strains. They use a variety of labs across the country and so that's it's considered a standard but it's not definitive because there are plenty of ways to dose plenty of ways to deliver it plenty of molecules out kit but if it doesn't work it's another data point and so we it it people say maybe it doesn't. Work Johann Orix Switzerland says if you give are too old mice it does work took less than a little bit. We don't know about an we're running that expressed express my live. That's no secret so we'll see if that works on mostly I think. It is a good start. What I find somewhat frustrating is that they've never asked me for advice on how to dose of what to give anything so. I was surprised as well that you weren't involved in that now. What you're basically saying is look in the end. Does this stuff clinically work is is all that matters because there's really smart people out there saying show me the evidence that increasing intramuscular. NASD matters what if it's in different what if this is true true and unrelated unrelated very recently paper came out looking at megadose of oral nicotinamide riboside with Tara still being in patients with hey L. S. and he was a miniscule study that had as many dropouts as it had computers if not more but the gist of it was that on some would appear to be subjective measurements of quality of life there was an improvement in patients with LS taking this very high dose of Nicotinamide and my driver's side with terrorists elvin versus those taking a placebo and what they miss some cutback function as well as I think they measured one pulmonary function called forced vital capacity yeah so so which is how much air could you blow. It should be a pretty important pulmonary function which is one of the more important things gets degraded in somebody with a ls so the point is for a very small study. That obviously didn't have any hard end points. It looked like a success but I can't help but think of what you talked about earlier. What if this is another example sample of something where to see the effect you have to be testing it in the most distressed organism you don't like to talk about people in that terms but a person with a LS is under far greater distress than you are and it's certainly possible that in somebody who is that close to the physiologic limits of survival you can actually see a small benefit which I think is what that study assuming that study is replicated. Which of course is to your point? That's the nature of science I mean. Each experiment is nothing nothing more than a way to ultra probability of something likely to be true but this would now make that case but that was my reading of that study which was is interesting but I wanna see that in someone healthy. I WanNa see that in someone for the same reason I wanna know what Metformin is doing in somebody who doesn't have diabetes beatty's so someone really smart. I forgot who it was on this topic once speaking very specifically about this there is so much smoke out there that you have to believe. There's a fire there but I just don't know where it is. I think that's sort of how I feel well with the ritual experience that I've had in my career and with an it wouldn't surprise surprised me for what you said is true. which is if you're in peak condition and you're young? You're not gonNA see a big effect if you've got. LS Or some other disease that gives you low energy levels us so to ones and not working the way they should then. You'll see the benefits that seems to be a theme. That's emerging. If that's true. That's still good because we're not always GONNA be super healthy or able to run every day. There will be a time for the alias patients. I'm sure there rejoicing this could be sure that study was the first real real believable hint choosing my words very carefully but that one looked like there may be some fire there in the LS patients now. It was a p value point when I wanNA know some subjectivity but if you look at placebo versus the control that placebos got worse and the drug experimental most of them went up in improvement in terms of life measurements. You didn't have to squint to see that result which was a nice thing. We'll say again you got to remember. They don't have pure and are in this drug. It's mixture of its <unk> hoping to are still being is very similar molecules whereas virtual I was Gonna ask you. The study was I believe I believe they were using twelve hundred milligrams combined so it was a thousand of our two hundred of terrace dilip six. Those capsules does that they sell. That's right now. The question is is Tara still being milligram per milligram as potent as resveratrol in other words. Were those patients only taking one fifth of their dose of a strategic activator that you're taking yet. I would've been so in other words. Two hundred milligrams of pterostilbene is about the same as two hundred milligrams of rhys retrial. No one knows that but Brazil troy is again. These missiles resveratrol has three little arm sticking out of two reigns and to those methods intersting so it's very similar molecule kilter is virtual whether or not it's period. I don't believe it is some marketing says that it's better. I haven't seen any data on that. If this study were done without the terrace delbene it might be more interesting 'cause we could then someone's like you'd almost a third arm that had either an are only or p. T. ONLY PT for the listener being terraced hoping yeah well. That's the best way to do an experiment but probably an extra few million dollars do that interesting so what is the current field looking looking like on this or two and activators. Are there others coming down the pipeline as your lab working on next. Gen Sir to and activators what we pushing hard on our pro. Roy Drugs of any bruce hopefully get around all the liabilities that we've discussed about these energy boosters such as better absorption not adjusted by the got activity is released in the gut doesn't full up in your fridge. These are all good things and hopefully is more potent than the natural molecule and and those are I've been working with a team of chemists lost five six years with hundreds of different molecules that been put at least through animals and hopefully one day will be put into humans. Humans are most advanced molecule in class is human studies right now at the Brigham Women's Hospital in what type of patient with these are healthy volunteers phase phase one. It's a phase one so phase do would be if all goes well next year and what type of patient do you think would be most applicable. KONTA voltage what the company's thinking because they paying thank for it but I can't say that they're looking at diseases that are not common and so very similar to what you're sorta like this example of the people who are closer to the metabolic or to the sort sort of cliff edge. We'll their number reasons for doing that. One is that there is good animal models for some of these diseases with these molecules and relatives of them have worked but also there's is that business reason which is that trying to make drug for Obesity Orlan. Javadi is currently <hes> no one would give you any money to do that the very difficult and so what's hot what people want to see his foss track for disease is has an unmet need patience demanding something from the FDA and that there are actually bonuses incentives that the government has put in place to encourage people to make drugs for those diseases as well. We'll David the last thing I want to talk about. Is How in the hell did you make those beautiful beautiful drawings in your book <hes> well. I was surprised to learn that you had actually done those your actual artist artist. You're an artist who masquerades as a scientist while my enemies would say the office but I do drawing as a hobby and it was actually a real pleasure that I was forced to due drawing hadn't done it since nineteen eighties but I used to do a lot of drawing is going to be an artist or at least a an architect paid artist. I very Nellie became a a computer graphic design guy before <hes> such things Pixar I love biology light ended up falling in love with lab work and aging was the biggest thing that needed to be solved rather than drawing pictures but the way ended up having to draw elise pictures which are you haven't seen the booking on the website lifespan book. Dot Com and I've I've got a lot of drawings out there even posted or by the time people here this. The book will be go fantastic so unfortunately the reduced to the size of postage stamp. I drew them the size of foot by afoot on a sketch pad. That's what makes them look so impressive. That's what they look like. They're drawn by a computer. They're so good because I'm trying to imagine you actually drawing them that small not that it's any less impressive that you drew them at larger scale but the detail is unbelievable. They actually look like photographs that were then rendered into sketches. That's that's how impressed I that's how I originally did it and the lawyers at Simon and Schuster said you can't even use that you'd have to go and get permission from everybody took the photo that that I was <hes> rendering so I had to go back and physically make original art that I own. I had twenty days to draw twenty-eight human faces and so it was fun. I really enjoyed it. I'll get home sometimes at ten o'clock at night and have someone's face to draw on what was actually helpful was that I couldn't obsess over vert 'cause I that kind of personality of perfection that was forced finally got an hour or two to draw this now. Just sketch it out. It's actually wasn't that hard because these as you can hit control sleet and oral deleting get rid of what you just don if you don't like it in the old days with India in Q. Maker sketching a mistake forget it. It's over start again. Wasn't that hard but really really enjoyed using that other part of my brain that usually don't use well David. Thank you very much for stopping by today. Congratulations on your book. I know how much work goes into that and I think people are really going to enjoy enjoy it. I think it's so funny like it's actually a pretty different look at a pretty common topic. I haven't done the Google search on how many longevity books are an Amazon but you you probably need scientific notation to count it and most of them probably aren't worth reading to be honest with you but yours absolutely is. I think people really enjoy it while it's fresh. I look I think from today. It's been clear that there's a lot of new stuff in there. It's a different way of looking at aging this whole information theory idea it's new. Nobody talks like I do about aging very if you are so should say and what's exciting about it. Actually as I was writing stuff down as it was happening in the labs of redesign just learn about what I do every day in what my family family does and what I think the future look like but also what it's like to be part of these discoveries and how it feels and for the students and the impact on potential impact on the world so yeah. I'm pretty appreciative that you've had me on allowed me to talk about. What's in the book. Look forward to reading yours. When it comes out to oh well I'll be a couple of years from now but that that'd be great. We'll turn the tables anyway. Thanks so much David really appreciate Peter's. You can find all of this information and more appear irritate. MD DOT com forward slash podcast there you'll find the show notes readings and links related to this episode can also find my blog at PT MD DOT COM now. Maybe the simplest thing to do is to sign up for my subjectively non lame once a week email world update you on what I've been up to the most interesting papers I've read and all things related to longevity engevity science performance sleep Cetera on social. You can find me on twitter instagram facebook all with the idea. Peter at md but usually twitter is the best way to reach me to share your questions and comments now for the obligatory disclaimer. This podcast is for general informational purposes only and does not constitute the practice of medicine nursing or other professional professional healthcare services including the giving of medical advice and note no doctor patient relationship is for the use of this information and the materials linked to the podcast is at the user's own risk. The content of this podcast is not intended to be a substitute for professional medical advice diagnoses or treat users should not disregard or Oh delay in obtaining medical advice for any medical condition they have and should seek the assistance of their healthcare professionals for any such conditions lastly and perhaps most importantly I take conflicts of interest very seriously for all of my disclosures the companies I invest and or advise please visit Peter Attiyah M._d. Dot Com forward slash about.

David Sinclair Shannon Sir Protein professor Steve Horvath FDA Glaucoma celtics Peter Attiyah AMA nicotinamide director Peter Drive Sir Conrad Waddington MIT doxycycline MD DOT COM
Nir Barzilai, M.D.: How to tame aging (EP.35)

The Peter Attia Drive

2:47:29 hr | 2 years ago

Nir Barzilai, M.D.: How to tame aging (EP.35)

"Hey, everyone. Welcome to the Peter Attiyah drive. I'm your host, Peter. Drive as a result of my hunger for optimizing performance health on jeopardy critical thinking along with other obsessions along the way. I've spent the last several years working with some of the most successful top performing individuals in the world, and this podcast is my attempt to synthesize. What I've learned along the way to help you live a higher quality more fulfilling life, if you enjoy this podcast. You can find more information on today's episode and other topics at Peter MD dot com. Everybody. Welcome to this week's episode of the drive and happy new year to everyone took a week off as you probably noticed. So hopefully, everybody's ready to jump back into this fun stuff. My guest this week is near Barzilai. And if you're at all into the space of longevity, he'll be no stranger to you near is the founding director of the institute for aging research, the Nathan shock center of excellence and based biology at Auburn Stein, he's completed two fellowships one in metabolism. At yale. The other in endocrinology molecular biology at Cornell, he directs the longevity genes project, and in my estimate near is probably the most knowledgeable person ever on the genetics of longevity. And we talk a ton about that during this episode. He also is leading the effort to test metformin in a prospective clinical trial for non diabetics with respect to aging, and this is referred to as the tame trial. We. Get into that obviously in detail here and also will use a lot of the data for that in the show notes. This is in many ways, I think near is probably one of the most insightful people when it comes to understanding the clinical benefits of metformin. And we talk about that a ton. We also talk about insulin resistance. I can't resist the urge no pun intended. I guess to get into sort of a detailed discussion on what I are is with sort of people who are really deep in the space. We talk a lot about I Jeff and growth hormone. And I gotta tell you. This is a topic that you've probably heard me waffle on a little bit because I'm still really kind of on the fence about this relationship of I G F G H centenarian data point in one direction. I think the EPA Miala g outside of centenarians point in a different direction. And of course, none of this really speaks to the question. I get asked constantly, which is do you think administration of growth hormone is beneficial from a lifespan or health span perspective, or do you think it's harmful and truthfully? I've always leaned towards the. Harmful side, but we get into this in detail in near offers. Some great insights certainly for me. I was really helped by this process. We do go back and talk about the centenarians. And because I'm in the midst is some of, you know, writing this book, I'm knee deep on health literature. And so it was really great to kind of clarify a few things that I think even if you're not steeped in this stuff what you'll find very interesting. And of course, we talk about all my other favorite topics like Ataf Aji, caloric restriction. We even get into a little bit of the stuff around any D And nicotinamide riboside and things like that. So overall, I think this is a bit of a technical episode. But not that technical we certainly done more technical stuff. The show notes will be valuable as always especially for show of this nature. So with nothing else to add please welcome to the show near Barzilai. In your. How are you? I'm terrific. Are you? I'm good. I can't believe not only did you make it down here on time. But you made it down here ahead of me at my own place. Nice to stay on. Yeah. This is this. I don't know how these these days is this weather, so unpleasant. But yeah, you beat me here. I if I was a bit of a bit of sun pleasant for you because you're in California, most of the time. Yeah. I think that's part of it. But you're from Israel. So this has to be unpleasant for you to Israel was too warm for me. I'm okay, got it. Speaking of which so you were born in Israel, you spent how long were you in? Did you serve military time? There ESI served military time, I was in nursing and medical student. I went to the technique medical school. I went into DASA hospital for residency, which I finished and only then I came to the United States that was a teal with Ralph diff'rent Zo doing 'em topples. Actually, I was looking at the mechanism of action of mid forming a nineteen eighty-seven before it was approved for using the United States. There's a. Deputies connection to that later. And then I went to Cornell for an endocrine, fella sheep, and then I was recruited to Einstein. And so my first part of my life was metabolism. But then I started doing what I really was interested in this is aging in the biology of aging, and I remember reading a quote once from you that said may be paraphrasing. But metformin is the reason I came to the United States will in a weight was, but this is life in retrospect, right? I wasn't really expecting. I was done with mid forming nineteen eighty eight that was down with forming Antilles started again about three four years ago while I can't wait to talk about metformin because they're probably I'm trying to think if I think four or five eggs molecules, which is just the terminology used to describe anything that you ingest or take that comes outside the body. So I would include drugs supplements hormones anything in there. But when you lump. All of these things together. If I were to say, what are the three or four of these that I'm asked about the most frequently from patients, or frankly, anybody if I met at a party, and I let it slide what I do for a living. The first question is should I be taking metformin, and there's usually a handful of others that they wanna know about IB taking nicotinamide right beside. They usually don't say that usually say should I be taking any or something to that effect? So it's wonderful that we will speak today because few people can speak about metformin the way you can. And so I'm really looking forward to that. But before we got on that path. I do still want to kind of understand a little bit more about your journey and your interest in chronology, did you know from day one when you entered the field of medicine that this was the area that you want to study. Yes, I was interested in aging from the time. I was pretty much thirteen and spend weakens with my grandfather who was telling me his life story and. He's life story wasn't easy. And he did let's physical things, and he dried this woman any did this and that and I'm looking at the man who was then sixty eight years old that walk slowly, he's obese white hair. Any just didn't look like somebody who did everything he told me to do. And you know, they say that children heavy machine -ation, but most kids don't see their Crin parents as what they will be right. They see them as I don't know how they got there. And this really stuck with me. And I started to be interested in the biology of aging when I was for example, when I did my residency I always was interested in how not what's the age of the patient, but doesn't look older or younger than his age. I kind of realizing to Italy that there's. Chronological age and biological age. And won't what is this differences between the biological and chronological age in a course is the physician it looked like endocrine is a good place to start because you knew that there's a lot of the chronology Neiji, and you assumed that hormones are going down or some are going up, but if you could fix that maybe you could fix a lot of aging now everything happening my life was fascinating from the biology of aging replacing the hormones wasn't really part of. But we'll get to going to the hormone thread. The most obvious example of changes in hormones with aging. Of course, occur in women where you know, they have this very abrupt change in one of their undercurrent systems this androgen system. Did you think about it? Even more broadly than that, for example, like what was happening in firearm hormone, and what was happening in fuel partitioning hormones and other things like that. Oh, absolutely. Absolutely. But. I'll tell you to the point when there was a discussion whether to do the women health initiative, you know, many people thought this is a waste of time. You know, we know that estrogen is good for women. There's lots of studies like that. Of course, it's majoring aging, and I didn't look at the this simply for maybe two reasons. One is men are also aging and in several ways similar to women, and that's not an estrogen story, and it wasn't destroyed decrease wasn't really as dramatic estrogen decrease. So I I didn't I thought that there's a lot of aging that's done without estrogen. Let's start with that. And also, you're replacing just one hormone with lots of Ramona's are changing it in look like a good study to me, well, especially at the time, and I try to be temper my criticism for that study by trying to have some empathy for the fact that the investigators were dealing with what the treatment pro. Calls were at the time, but to use oral estrogen that's conjugated Ecuadorian to us. Thank progestin, not even actual process thrown in there. You could come up with a list of eighteen things that in retrospect are so obvious. Why that study was a failure? Absolutely true. But the other part of that is that the way to show effect of estrogen in animal models was to take their ovaries out and give them as Trajan. And then you could show could do lots of vacation. It was good so estrogen is a good hormone on a young body. But then there were studies that were hardly published. But I was aware of them of taking all animal, you know. So you could take the young animals in just one center in Houston. They did it. You took the young animal. You took their ovaries out. You gave them as Trajan employed, a stroke model. Okay. And when you give estrogen the stroke was smaller and every. Thing when you did the same in older animals, the stroke became worse. Okay. And they couldn't publish for awhile. Because they said, well, it's all Denel. So they've other diseases or other things but every experimented estrogen in old model. Wasn't was the opposite. Not only that he didn't affect it was the opposite. Which would happen. You know to the w Gye in certain ways. Although I still think that the it was probably the breast cancer that garnered the most headline in the WHO, and actually that's interesting topic, which will be going into great depth on another episode. There's a great book that just came out the tackles, this that goes through the history of the W H I at what point well, let's go back to the metformin thing, actually. So it's nineteen eighty seven. And you're thinking like, okay metformin is the next line of agent. We will use to treat type two diabetes. So metformin was already in in clinical practice in Europe is correct. Correct. For many. A years how many like twenty or thirty years so mid forming few years ago was sixty years. So we are talking about, you know, nineteen fifty or something nineteen fifty nine hundred sixty when I was in Israel, I prescribe with farming. You know, that was the first line for type two diabetes. What took so long for it to come to the US? That's a terrible story that still continues. You know, the FDA said, we don't know we don't know that the form is going to be effective in the relation in the United States. So you have to do the studies in it was Bristol Meyer relieved that got to do the studies in basically they had to face three study again to show that metformin forming is effective Sultani Lereah iza as an indication for type two diabetes. And if even then the idea was that it will be good only obese people. Which happened not to matter much because all type to be seen states where obese, but it was really matter of regulation in part of having regulation was that the FDA more studies to understand the mechanism of aging at forming and in a certain way, maybe they're right because Mott former mechanism of action is really complicated. And I'm not sure that today as a new drug it would be approved. Interesting. Why where do you think it would fail in safety or efficacy? No, it's not in mechanism in the in the inability to elicit Mak right went when you come to the Dan, you say, you know, we've done that. And we've done these animal, and it was done these sales, and you're trying to show what is the major mechanism of action you you would have failed. So what I showed in Newman's is that. Admit forming targets if glucose production or the insulin sensitivity of liver, and that's the major mechanism of action. Unlike for example, Sufa Nina RIA that increasing Suissa creation right or TC dis increase the incident sensitivity in the muscle more than in the levers. So this was the mechanism that you could pick to the FDA, but it's really not the interstellar mechanism of mid for me. So at the time was it understood what metformin activity was on complex one of the mitochondria. Now, not really this came later. I I don't know what year, but he came later came when the seahorses essays were developed to show really which might Connery in which possibly of more might to Conrad you have changes. Maybe for the listener explain what a seahorse ASA is seahorse essays an essay too. To look at my Takao drill action. Whether you extract my country, our even tissues, it really shows some relationship between oxygen consumption in relationship to philosophy and it's very sensitive to look at some of the effects of drugs that are interferon might contra action or decrease might con- relativity in the indirect calorie Matry of the might occur riot right indirect because it's a provocative test, Johnny. So yes, metformin was discovered from a plant as well. Correct rights. It's a French lily firstly, obviously in this was discovered been forties or fifties. Correct. The first thing that happened. The was a drug by the name of informing a cousin of mid for me, which apparently is much more potent. It's much more potent. Because unlike mitt formity dozen need it transported to get into. The sales on the other hand it was associated with a lot of luck tick ac- doses in it was considered unsafe. Eventually and then mid forming was a safer part with much less of electric those side effects. What is the mechanism by which metformin 'cause like the doses because in all the use I've seen of metformin clinically. I've never seen a case of it. Which is not to say, it doesn't happen. I'm sure it does in you could stack risks by taking someone with renal insufficiency giving them contrast in tons of metformin, but in medical school. This was like the board question you got asked every single test. What you have to worry about lactic acidosis, what's the putative mechanism by which that happens? So first of all, I would tell you that in my study in the eighties every patient that we gave its forming headed increasing lactic 'Seat from what to what Miller within the. Normal range. So if it's too was the cutoff the cutoff. So it was you know, between went from wine one point five towards the two. And sometimes even went over the two, but it wasn't really anything associated with the does. There was no change in ph. Now now, no onion gap not to anything like that any probably has to do. I I don't know that I can tell you for sure, but it has to do with what happens when complex swan part of the bully effect when complex one is in heated, but there's lots of speculation, and I don't really care to comment on on that. But I think what became clear there is all we call it chronologies it Malla, it's mid forming associated lock tickets those. In other words, we moved away from it forming causing guts to this association because it. It's if anywhere described more in people that have kidney failures or have heart attacks or something and had locked dozen wear on with forming too. And that was kind of this association, but it's not clear to me that they're truly people who developed lactic acidosis from informing that these just because of Mott forming and not associated with something else. I'm glad to hear you say that sort of generally been my bias. But I'm I'm happy to be corrected if that biases incorrect. But, but yeah, I've always thought that frankly, so many of the drugs that we're really interested in now as we look back from aging perspective, whether p metformin rapamycin, so many of the negative side effects that people typically associated with those drugs are very difficult to isolate from the patients in whom those drugs have historically been given. And so it's nice to hear that that Malla is now being generally recognized. As an alternative of viewpoint to that. You know, metformin is to me an interesting drug from a diabetic standpoint. Because and I don't I don't know that this was appreciated in the eighties. In fact, I would suspect it was not because there's really two macro strategies for improving type two diabetes. You can obviously the highest goal is to control glucose levels. So to to regulate the degree of glucose in the blood, but you can do that through at the highest level two ways. You could increase insulin either exaggeratedly or through increase, insulin production pharmacologically, or you could reduce glucose, and of course, metformin falls into the latter category of that or increasing muscle insulin sensitivity for to enhance glucose disposal. Today. It's generally regarded that while both strategies will have an equal benefit on the micro vascular the glucose lowering by insulin lowering. So the less glucose production strategy has a superior effect on the macro pass catcher. And therefore metformin would be a better alternative to for example, drug. That's going to increase insulin. Production of the pancreas was appreciated at the time. Meaning when you were doing this in the late eighties. How potentially beneficial this drug was well adept time in the United States. It was all about insulin resistance, you know, people Jerry riven rows DeFrantz Zo, the people at the NIH Ron con where all discovering the insulin receptor discovering, insulin resistance discovering this association of insulin resistant with the Bullock syndrome. So it was all we all had the bias that the major problem with type two diabetes, insulin resistance. And you know, we know now that it's total collaboration. Yeah. You increase insulin resistance and the punk ass have to secrete more insulin, and we Uman's at least in the condition of our environment of BCC everything. Many of us. I would say forty percent cannot deal with it. And we become diabetic. There's the Starling curve of the punk-rock. You know, like like for the heart that increasing soon secretion at some point you cannot increase insulin. Secretion you become the basic and then insulin secretion decree decrease and so- insulin resistance was a major way. And that's why mitt forming was a good place to come with. You know, at least it it affects mainly the potty glucose production. Rather than the muscle though. I have to tell you in vitro on muscle specimen. It's an insulin. Sensitizing the muscle to. Let's talk about this idea of. Insulin resistance. I think there are a few terms that leave me scratching my head more than that one. So this is an example of something where maybe five years ago, I thought I really knew what insulin resistance was. And I think today, I'm pretty sure I don't know what it is in the sense that when you take the typical FINA type of someone who's insulin resistant. What do they look like bio chemically, and and the morphology, right? So they're hyperinsulinemia. They have elevated levels of glucose, they probably have some degree of obesity or outta positi. So what does that mean? Because clearly there fat cell is quite sensitive to insulin. If the fat cell ever became resistant to insulin. You could not reestablish fatty acids, and you would have an endless stream of policies exiting fatty acids from the fat cells you'd actually be quite lean. There's something going on in the muscle that clearly is resistant to the effect of insulin. But of course, there are both insulin dependent and insolent independent means by which we can dispose of. Glucose, and this is were coming back to what you said a moment ago. I actually wanted to ask you that question, which is that we'll park it. But the question was does met four men participate in the MP K driven insulin independent modality of glucose disposal. You're nodding. So I think that's a yes. And we'll come back to it. And then there's the liver, and this is the one to me that is the most complicated and the one I'd like to begin with. So before I ask you to elaborate on the specifically what is meant by insulin resistance in the liver. Am I complete moron for not understanding this? No, can I make a little bit more interesting even because I need to bring it to aging. Yes. I would love to talk about the Abe's. But let me just put up front. I don't I'm not sure that that the beaches property of forming a really the aging properties of mid for me. Okay. This is my vocation, but let me go back to insulin resistant because in in nineteen. Ninety-seven is science paper appeared that made the best day of my life and the worst day of my life. Okay. Wow. What was the paper? The paper was taking inimitable. Okay. Primitive model? Decreasing the insulin sensitivity, this is known as the Duff to model, and when you do that the Nemet owed accumulates fete in their intestinal sales. So they are becoming visceral bee's and they leave several times longer. So why is it might the best day in my life because you could with one genetic manipulation extends lifespan significantly that meant going from hope actually from nothing froze, the cynthia's paper would know that's the Gary roof game. But at the same time, Cindy, either adopt sixteen Tom Johnson has had the age one model. There are several papers that came in all of them said, hey, we can change a lifespan. And the exemple was always ancient since the end this mutation to be clear between Daf two sixteen and the dietary manipulations there are several permutations of that see elegance model, but just to make sure I know which paper were talking about this was only attenuation of Taft to nothing to death sixteen and nothing tonight. Terry, right, right. Can you just for the listener define? What is the analog of daft to Daf sixteen and us Duff to ease the insulin receptor and doffs sixteen is the fuck. So the folks oh transcription factor. But the point is at this time that you took a worm that normally lives two weeks, and you turned down its insulin receptor slightly not off correct. Right. But you made insulin resistant, and it was accumulating fat. And what was? Cy bringing into the field. I was saying the major reason for aging is this insulin resistance syndrome, and the main part of the insulin resistant is accumulation of visceral fit. And so the premise was good digs Empel was disaster. To me, I had the JC I taper adept timing press really showing with MRI pictures, how caloric restriction decreases, the visceral fed I was talking about the biology of those fed and stuff, and it was a major power Dokes for us in the field. And how we continue if we're saying insulin resistant is good for longevity and everybody diabetes news. This is a disaster. Why am I telling you that because I learned later I was thinking later on experiments that I've done out. So first of all experiment that I've done that was very conclusive was I took. Bunch of Ritz hundred fifty actually and all of them underwent surgery after puberty in some of them, I removed their visceral fat depots by surgery and in the other. It was a sham procedure just moved but didn't remove and we had three groups in the experiment. One was Ed Lee, boom, feeding the second was caloric restriction. This is the control they would leave forty percent better. And the third group was Ed Leedom feeding of the Retz that their visceral fat was removed. And I said, you know, without the visceral fat even with nutrients, they leave longer and they actually leave significantly longer than the Leedom by twenty percent. But not as much as the caloric restriction. Just make sure understand you had a two one ratio of your animals because you had no I had three groups three groups, but one of all ad lib feeding of the visceral. Fat removed that was right. And then of the ones that had sham surgery. They were randomized to ad-lib versus CR, correct? It's really showed that visceral fat, the removal of visceral fat had major effect. And when the animals who had the visceral fat removed were autopsied or whatever the word is for rat. Autopsies had they re figured out a way to reaccumulation visceral fat or where they accumulated now. In fact, when you do this procedure after puberty if you do it before puberty, they accumulate visceral fit, otherwise don't accumulate much visceral set did they have changes in subcutaneous fat. That's a good question mice heavy when you do it and Retz do not what do they ultimately succumb to? They all die from the same thing only different times. Which is what cancer? Yeah. It was Sprague doling so kidney disease cancers were the leading causing debts. So you basically got half the benefit of CR by doing this. But. Doom but without visceral fat. So you understand it's very sorry. One other question near was there any change in their health span or their spry nece? Yes. There was a helsmman. In fact, what happened to the Libby doom that lead doom starts losing weight at the end of their life and the ad lib doom with visceral fat have still gained weight after the others. You know, it was a significant change in weight. And then there's a whole hell spend their insulin levels and other things that we've been we've down in parliament. So they were they were healthy, and there were healthier for longer, which is kind of the experience that we do with enema moms is it possible to take one of those rats and either through caloric restriction or other dietary restriction get it to breezy to the point where you did the surgery, but without any visceral fat, and then ask the question if they've gone through that period of development without developing visceral fat too, they have somehow. Protection from the diseases that come even if you feed them, add Ledum thereafter. So we did this experiment in Zuqar fat animal or Zucchero BT Santa mo-, and we took their visceral fed health. Hell people what the rat looks like. So the rats are reds that are really really really obese hungry all the time. So they have hyper Faiza they can't stop eat right bit because they don't have the leptin receptor. So they are hungry all the time. And they're not because you try to come close to them. They think your fingers food. So they're eating all the time. And we did surgery on them before puberty because they became obese really much before puberty. And what happened is by six months? They all become diabetics our animals up to four months did not become diabetic. And then between four and six they became diabetic, though, took their visceral fit. But. What we found out that eighty percent of the visceral fed grew BIC. So we actually had the perfect experiment as long as they didn't have Israel fed. They didn't develop diabetes once they the viscera Fethi develop diabetes. But I wanna make one other thing if you took that group and who already developed diabetes with visceral fat, and you just remove visceral fat can reverse the diabetes now, I we've never done this experiment. Don't know because we're interested in age. But I'm telling you all to make one point because so far the part looks just got worse. Right. The Nimick dotes with incidences in visceral fat leaves longer, and we showed that mammalian leaf longer. If you take this visceral fat and make them insensitivity whenever we take visceral fed we make the mornings insensitive. Okay. Until I realized one thing it takes me few hours to make Ritz insulin resistant. I give them glucose. I give them free at the ESI. I give them some other things. I can make them insulin resistance very rapidly. So it I used the as you see we can do the chronic incident. Resisting few hours? Okay. You're just load them when nutrients you become insulin resistant, but then I thought of the aging part when you get glucose to the muscle. The glucose goes into the muscle. If you're not moving the muscle. It's not going to turn more glucose to energy. Will switch from free fatty acid to glucose, but that, but there's no more glucose burning. So he goes to glycogen, right? And he goes to glycogen, but you keep on putting locals in the muscle. And there's just so much like agenda that the muscle can store. So the muscle has to become insulin resistance. Okay. It's a protective mechanism. There's no evidence that the muscle can in any way, shape or form undergo to Nova like Genesis and create any of the fatty acid is there to create any of the fatty less from from now not there any evidence that muscle can under can can carry Genesis. I don't think so I I don't think so I'll have to think because I have different. I think about it. But but the point is the okay, I understand your point. I I don't think if anything there's no much the glucose the muscle tells the glucose, you go somewhere else, you know, you go to fat. Okay. So the only organ that can take in completely excess amount of Lukosi. In the end has to be the liver because it had leased has the capacity to turn excess glucose into fat, whereas all of the other organs are going to be saturated. That's true. And that's part of I think where the glucose is knowing. Okay, too fat into liver. Okay. So what am I telling you? I'm saying that insulin resistance is a protective mechanism. It's a modulator. It's a stress response something. So now, I understand why a stress response mechanism in one animal caused them to leave longer and in another animal, it's a pain in the butt. So I went and I wrote this review with with Luigi Ferruccio. I wrote this review where we took all the animals that had problems with their insulin sensitivity the animals that are insulin resistance and leave longer and the animals with insulin sensitivity that leaves shorter. And there's a huge list of it rep Amai. In is an example, right rep amazing causes insulin resistant the animals the best intervention in in rodents. There's the PT one transgenic animals, it's very insulin sensitivity, and he's has huffed the lifespan the lifespan of a wide when you say insulin resistance, insulin sensitive. Are you always referring to muscle? Are you referring to liver? How are you defining them will in this sense? It was everything it was I arrest, for example, iris one IRS to know cout, some of them owning the brain. So it was really insulin resistance everywhere is IRS one found in the muscle and not deliver. No IRS one in Irish to are everywhere, but IRAs stew is more in liver. Like, the the sort of have selective express. Right. Yeah. So just translate IRS one insulin receptor substrate substrate. So let's talk about exactly how the muscle takes glucose. So we are walking around if I bowl issue with glucose right now and your blood glucose rises from wherever it is right now ninety two two hundred let's give you an enormous bowl of glucose. I double it. So you're up to one hundred eighty milligrams per deciliter this very high screaming high level, which by the way, only amounts to an extra few grams of glucose, but nevertheless, what is the chain of events that leads to insulin being secreted and the muscle. Ultimately disposing of that glucose both actively or passively will there be obviously secretion to insulin. That's relative to your Lucas level. And so that the beta Sal is the sensor right an outcomes insulin. And now what is insulin doing to the muscle and insulin through the insulin? Receptor will. Get translocation of the glut for those of the glucose transporters that are the major glucose transporters muscle. It will go from an intracellular pool into the plasma membrane integrated in starts getting locals like crazy into the and that happens quite passively. Meaning once the glut four transporter is translocated across the cell, membrane glucose can passively rush. Incorrect, it doesn't require ATP to bring it in a great way of any sort. Correct. An infected has its own intrinsic activity. That's not the energy dependent. So he can go faster or slower by by different ways. Now is there another method by which without insulin? We can get glucose into a cell that somehow relies on AMP China's not named Py kind. But there's none insulin. Mediated glucose optic. In other words, there's a way for Lucas to get up without the incident, and we know that from hyperglycemia clamp and from. Other things that when we can move into their or keep insulin level at basil. And still there's a substantial Luca's optic. That's happening. So yeah, we know what's the mechanism of I'm I'm not sure I know it also seems to be enhanced by exercise. That's true. That's true. This ninja is the non intimidated glucose update something that is exercise dependent to mellow. That's what now industry your questions. AMP kind is just part of the net. And I I don't know that I only have one patient in my practice who has type one diabetes, but he is such an interesting patient because of his incredibly strict dietary control and his unbelievable appetite for exercise. And he I've never seen a higher level of adiponectin in a human of never seen a higher level of sex hormone, binding globulin in a human way. Which are basically, and we know how much insulin. He has because he injects it, and he injects so little insulin to himself, and yet can to you know, he has a hemoglobin A one see below six using six to eight units of insulin a day. And so what got me. That's what got me very interested in this. Non insulin dependent glucose uptake. Yeah. I'm not doing this research anymore. I used to in front of that I- glucose itself can modulate local China's activity in the lever. There's a lot of things that happening. And of course, there's coordination between the fat, and and the liver, and then I started being interested because we can do things to the hypothalamus and take over these insulin and muscle in fat and liver. We can do it all from the brain. Isn't that amazing? Well, just because I'm so fascinated by this. And I think it will help the listener to understand the complexity of what you just said if I took an animal and put a. Elision into the ventral part of the hypothalamus a normal animal. What could that do what would that change about its metabolism will that would increase basically, food intake and change a lot of the peripheral physiology? But we do basically the opposite. We give insulin to Potala mousse or glucose or or lifting. Okay. And then we see what happens to the brutal birthday, those hormone levels are not increasing adult and not only that the liver is a good target to follow because what you can do with the liver. You can do selective of gotta me and everything that you did through the brain doesn't work anymore because it needs the nerves writes all explained to the listener what that means. So the Vegas nerve connects the body through this para sympathetic system. And of course, if patient has a liver transplant or if you do an operation where you sever the Vegas nerve. You sever that connection between the central nervous system and the periphery correct? And so we can do it's experimentally an end it will help us. See if it really how much of it is regularly. Mediated verses not or. Yeah. Or more nerve on the you know, the nerves because we do it's not only got to me we do a little bit a generic too. But it's through this the nerves and not through a chemical reaction on the liver. You see this is the problem with metabolism near the more. I go into it the less. I know it drives me nuts. My absolute knowledge increases incrementally. My relative knowledge falls precipitously. I think I realized that you know, what to ask. So you're undermining your own abilities. But it's really it's really the integrity of metabolisms really very confusing to explain so we will define insulin resistance at the muscle. Whether it be from an aged phenotype or a diabetic phenotype as a scenario under which a fixed amount of insulin hitting the insulin. Receptor produces fewer glued for transporters. Is that a fair definition? The definition of insulin resistance is really different in very simple. It's all about the glucose uptake in the muscle rates all about that -bility of in. Insulin to clear glucose. Okay. That's the only way we define clinically insulin resistance. Although that totally misses the point because those insulin levels have different affects on different issue. But for us, the insulin sensitivity is totally related to the glucose optic. So let me give you an example. So when I use an oral glucose tolerance test with my patients, I'm a bit of stickler. So if they take their seventy five grams of glucose, LA I measure their glucose and insulin at baseline administer the glue cola, thirty minutes later, sixty minutes later, ninety minutes later, and if I'm feeling aggressive one hundred twenty minutes later, we re measure the glucose, the insulin and the FA, then maybe even the peptide, but for simplifying it just the glucose and insulin. So let's assume you have to patients who start out with a fasting glucose of ninety milligrams per deciliter and six insulin of use of six. They both got their seventy five of glucose, and let's again simplify this by just looking at one hour. What happens both of them at one hour have arise of glucose from ninety to one hundred thirty milligrams per deciliter one of them did. So with a rise of insulin from six to twenty the other did it with a rise of insulin from six to ninety. They've both disc- disposed of glucose with equal magnitude would you describe them both as equally Enslin sensitive. It's a little bit complicated. You know, I full so let me just say for aging hundred twenties not enough in elderly the glucose owners, go. So the rising insulin is changing throughout normal physiology throughout individuals, and you must you might have missed some of the insulin peaks earlier on or later on. Yeah. The looking at thirty. Versus ninety as a big insight, and you're right. I mean Joseph Kraft who is a pathologist who has done a lot of work on this. He samples to five hours. Now, again, clinically that's challenging in the regular day-to-day practice. But in the laboratory, that's feasible and you're right. You can see so much happening beyond that. But I tried to pick an example that was as agreed just enough in its difference that the what I'm trying to get the difference in hyperinsulinemia, and whether that factors into how we think about insulin resistance. No, I don't think the clinical world is thinking like that is so I'm actually an active in the Colonel Steele see on Thursday, my Montag in town teaching fellows than in the elitist cleaning Montefiore hospital. So I am involved very much in these failed. And I'll tell you that we rarely measure insulin in any of our patients, but that's not really your patie-. That's okay. I'm talking about. What's the use of measuring in selene in type two diabetic patients? So it's a different issue. But yet this is sounds like there's a different insulin response. To lower the glucose design extent. 'cause the hypothesis would be that the patient with hyperinsulinemia is now demonstrating I mean, that's basically a harbinger of the first one who's going to struggle with Lucas disposal. That would be my hypothesis is the one who needed ninety units of insulin to dispose of glucose with the same efficacy as the person who needed thirty is sooner rather than later going to have a hard time disposing of glucose, when you know, there is another possibility that those are the people who get other diseases for like heart attacks, a stroke. In other words, there insulin resistance will affect a lot the way they do that they're Roddick Plock, and these, hyper and soon Niimi on organs that might not be insulin resistant, even on sales that not coming into this is so I would say that they could either the one who become a basic or the one we're going to get microbus. Serie disease much foster brings it right back to our observation of glucose, insulin micro versus macular, vascular that's very good point. So how does insulin signaling work to get glucose into the liver? The liver has different glucose drawn splitters blue to that. He's not translocated. And that these the major way by glucose gets into the liver. So it's a little bit different. But it's not a stimulated the same. So it's constituency expressed across the membrane. It's not stimulated really by insulating as much. So it's more gradient driven to get the glucose from the circulation into the liberals. And that's where the portal bodies. So there it's very sensitive to the increasing locals concentrations. Well, that's very interesting because it certainly there's lots of evolutionary reasons why that would be a fail safe, right? Given the importance of you would never ever want the liver to be denied glucose given that if you ever shut down the liberals ability to make glucose Mike calculation, you could live about six minutes. Yeah. Look, I was an intern of Sheila sharell, she's Dane she'll share look in England in Royal feels very known at Dala Giese than she asked a group of us. What's the main role of the liver, and I raised my hand. And I said it's to produce glucose that wouldn't my answer. And everybody laughed at me. And she threw shocks them in seven Justin wire saying I said because if you take the lever out and clamp the vessels the guy will die from hypoglycemia, which is absolutely true. Yeah. Yeah. It's. You know, maybe it's just because I'm in the midst of writing this chapter for my book about the liver. But I literally yesterday I sat here in my room and penned out the calculation of hundred eighty pound person with blood glucose of one hundred eighty milligrams per deciliter clamp deliver how many minutes until they die. It's about four under those under those conditions. Can you imagine that think about like what is beautiful organ has to do? But, you know, another thing to considering your example, right? So for example, elderly. Have enough insulin to suppress glucose production bloopers productions easier to suppress than it. Suppressing lower level of insulin. Than stimulating glucose uptake in the Muslim delivers more sensitive than the muscle in. So elderly have the ability to suppress glucose production because they have enough of insulin to do it. But when you start giving them food during the day they fail and they become glucose intolerance in diabetic, they might have diabetes. Although there Beza level are well just because of this this enough insulin to suppress glucose production and not enough to increase glucose optic. So the sensitivity of the tissues is really to incidents. Really part of what you're describing. If you look at the basil. It's very different stood challenge that such. Such a great point. And I won't I won't go down that rabbit hole anymore because I I would love to. But there's so many other things I wanna talk about near. Let's let's go back to metformin, and let's do it now through the context of an anti aging drug. So there's gonna be some people listening to this who already know everything about you. If for no other reason than the efforts you've put into tame, obviously, I wanna have plenty of time to talk about that. But let's back up for moment. Tell me when you first realized, hey, this metformin drug that I worked on thirty years ago. It's not just a great drug for people with diabetes. This could actually be a drug that helps someone without diabetes live longer. What was that a penny for you? So first of all they were studies on the biology of aging in rodents, and the I die which will be embarrassed. Now to forget, he's a guy from lending grat. That was the first to say I've done a rodent studies. And animals with mid forming on a totally L. Remember, it may be later, and he showed that a life extension extension increases in variety of animals to which he gave at forming that led to some study was his ipod assist. You. Remember, why what he what would he drove him to do that? There was never any hype clears fodder fishing expedition. It's even wasn't related to glucose metabolism necessarily. He thought that maybe there's an auntie Concer affect he looked dead. But then he got models that were hypertensive, and they also leave longer. So he thought those are different effect than then he considers to aging, but the debt time this was in the eighties when he started debt and. I don't. You'll remember should take more at forming. And he was pushing he was showing up in immediate showing. And so people have tried to do it in the United States, and they showed that there is a significant effect on insulin. By the way, the effect of insulating animals is ten percent not like Rupp mice twenty four percent. So there's a milder effects, but in every study, they showed it health span is improved by fifty. And so the effect on longevity was less than they'll -ffective health, by the way, that's perfect for what I'm trying to say, I'm I'm not for a longevity. I'm just for health span ride. So if we can leave LT LT LT die, that's fine. With me the squaring of the wearing rights where the jetty so he he started to uh CMO of his name is similar. So that's what awesome of showed people have started looking at that. They there several studies three. Audi's David also to name thoughts also leave longer and there's several effects on health spin in the biology of aging now. The reason there's a lot of NATO threading hearing my story here. Okay. But I want to tell you the the moment that I knew we have to do the study was it publication not in a very high impact journal. But it was an amazing study that could be done only in the UK because in the UK, you can go into pharmacies and look at prescription that they gave and you could follow that mortality of those patient because the NHS system allows you to centralize everything from prescription to usage to mortality exactly, and they're probably they don't need to d- to be the identify after mortality when you're dead. You're not prime. Any more K? So they did this study. So what they've done their four arms to the study. They came and took patients who are on Sufen Lereah twelve thousand patients. Okay. And they matched them to twelve thousand people without the Beatty's. Okay. Same pharmacies same doctors controlling for some other things. And of course, the people in sulfonate Maria had higher mortality than their control. You know? Right. Doubles. Of course, they had to be taking this oftener diabetes. So that's okay. Then they took seventy eight thousand people on myth for me and seventy eight thousand people who were non diabetic again matching them and the seventy eight thousand on metformin was met form in mono therapy monotherapy first line, right? And they watch their mortality so just to. Underline again, the people on metformin had diabetes control didn't have there are more bee's than the control. They also have more diseases than the control, but they had significant less mortality seventeen percent less mortality. In the mid forming group, and you know, the sulphonate Maria group was okay. So if you get less mortality with metformin when the setup is diabetes that really shows that mitt forming has a very important affect in Newman's as far as aging. What was the median dose of metformin in those populations? They were over thousand milligrams. That's it just a thousand milligrams. They intended more, but the average was about fifty meter about you know, I don't just fifteen hundred. Yeah. No thousand Manhattan story. They. This is a discussion there. I don't think they really could volley date the dose because an elegant thing to do if you have seventy eight thousand in your database is now stratified does. Absolutely. They taking five hundred thousand fifteen hundred two thousand they couldn't do that. And I really cannot answer you if you can get back to the data or not, I really don't know. The does the does which came from other studies. But you know, that's not the only thing we know about mid form that what was the what was the time course of that. By the way, do you know how years five years more tougher five years exposure to metformin or five years of prospective mortality following? No. It's will it's all it was all prospective study. Okay. It was all perspective study when they started. Okay. They went back. They looked at everybody on it for me. I'm asking is do we know how long the needed to be on metformin to achieve the Begnaud? We don't know. Okay. So we followed them for five years of mortality in a prospective cohort. But they could have been on metformin for five years or twenty five years. We don't know. No. It's newly it's newly prescribed for me. They were not more though. So we have normalized by duration. Lutely, absolutely, no. They haven't been on. It's forming before those are newly diagnosed type two diabetes so to near that's a pretty to be blunt goddamn staggering result. So my metformin moment nowhere near as dramatic as yours. Be basically came out of a research project. I did with two analysts in two thousand thirteen and I don't even remember what prompted the question. But there is a question we had internally about what was the benefit of metformin. Oh, now, I remember the quest. The question was was the relationship between hyperinsulinemia and breast cancer. This was the question we wanted to ask and as we dug and Doug, and Doug, and Doug and Doug something kept hitting us over the head over and over and over and over again, which was with or without diabetes with or without obesity with or without hyperinsulinemia any way you slice and dice the data of people with type two diabetes with and without metformin. They got much less breast cancer, which then Doug down a rabbit hole of they seem to get much less cancer. Which was you know, that was a big Hommant. Right. And they're hundreds of studies that showed the association between with forming and less concerns not only that less ole concert except prostate by the way, prostes hanging there, maybe a little bit. And when we went, and I'll tell you later, but when we went to the NCI to make them partners disdained study, it was really interesting. Meeting people what tame stands for tame stands for taming targeting aging with forming. And it's a study that's designed to prove the concept of aging can be targeted. But also or mainly for me is for the FDA to give an approval to an indication. That's like aging the first time I heard about tame was actually here in this city. I was having dinner with Steve Austin. It must have been in two thousand fifteen maybe fourteen fifteen Steve is a gem of a human being I consider him certainly one of the most important mentors in my exploration of his field of ages it we're partners. Yeah. Many ways. He's a great guy. He is. He is one of these guys that has his knowledge is out of control. You can't ask him a question that he doesn't know where to go for the answer. I have the highest respect for Steve. And can't wait to interview him here as well. But I remember him telling me about this. And my first thought was Steve that's a crazy idea. The drug is free who. Who the hell is going to pay for this study? And I h can't pay for it because they don't consider aging disease pharma can't pay for it. Because there's no way to make money on it. I mean, I I might pay like ten cents a year for my supply of metformin. It's a free drug. I said you're doing the wrong study man, you gotta do this with rapamycin. So talked me about the challenges of this. This is your proposing something that is really never been done before. Can I ask you are we going back to mid forming because you asked me about the Abe's, but not met forming action will ask me later. Absolutely. I cannot wait to die on metformin. Yeah. We're not gonna get off this topic for a while. Yeah. So so look if Amman Seraing now, why metformin north rope amazing. You don't need to answer that question. I was just sort of teasing Steve day. But will there are people who are asking? Of course mitt forming. We have preliminary data we have the concert. We have clinical. Studies clinical studies of mid forming did that Beatty's prevention program. Prevents their Beatty's. The U P E S prevents cardiovascular disease, the Alzheimer literature there to clinical studies to suggest that in mild cognitive impairment. It improves some domain, by the way. Like name recalling ac-. We'll we'll your after dinner. So there's lots of and safety. Look if we're going to heaven, you indication we don't wanna kill anybody on the road with rob my saying, we won't be sure, and it causes diabetes because to stickler atrophy and cut the rocks in animals. Okay. So we have to play it safe. So I would only add one caveat defensive rapamycin, which is with constituent dosing. Right. And and you're you're aware of this. Study's from Joan Manny variety of the last ones. Okay. So so my view on rapamycin is it should not be dosed every day should be selectively dose to target for complex one leave complex to alone. Exactly n I'll will get back to that. Because I'll tell you what we've done with forming for the biology of aging. Bart. So that's why the fi you look we are bunch of professors, including Stevens. Did we go to the FDA by the way, beautiful movie by Ron Howard? He went with us to the. FDA to the sandwich has it been released yet Storrow enters a year and a half ago. It's I'm sorry inches. It's called the age of aging. It's National Geographic. It's the best movie that was done ever on aging. It's really quite incredible. Ron Howard is in the rating, it I remember a tell you what I was having dinner with Steve at some point during he was in New York for that being filmed. Yeah. So, you know, so we're bunch of professors that are coming to the kind of telling them, you know, you know, that aging has biology, but these biology also can be targeted and they said, so what we said, well, if you slow ageing, then you prevent a bunch of age related diseases altogether. As said, we'll interested to hear. And we went through this discussion with FDA, I would say that the most interesting part and you'll appreciate it because your diabetes century. I see your. I'm actually not an petulantly purely age center. Eric, I are ability. But I'm I'm diabetes. I think of diabetes as a great example of what happens when you don't fix things earlier. So we told them basically we came. And we said we'll do a study and what we're going to see guardians us for disease and concern Alzheimer and mortality and diabetes and said not that BT's. What do you mean? Not that is not Beatty's. Look you diagnose their Beatty's first of all you diagnosis chemical on a chemical test. You know, you decide. Yeah. And only forty percent of them ten years later will get complication really not interested in diabetes women that the FDA actually say this absolutely absolutely said it, and by the way, I should add that there's another bunch of people who came to tell the FDA that they should allow forming for prediabetes because the DP said forming prevents diabetes by thirty percent. And they've said, well, if you think that's important why? Don't you make the diagnosis of diabetes in five point eight mobile onc-? You know, it's not up to us. To to do that. And they wouldn't give them any indication for prediabetes. That's a very counter intuitive point of view when you consider the long term, not short term short term cost burden of diabetes is relatively trivial. But it's that long term cost burden that becomes quite elaborate. You know? It's very boring with you because we have the same views. You're right. So yeah. So okay. But so we had to adjust their study where take the Beatty's as one of the outcomes. Yeah. And put in and just increase the number and take the BT south. It's not that. We're not going to follow there is. But the is not interesting. So the really the challenge was how do we define aging in a clinical study because one view is will because you can't use survival. Overall mortality will there's no there's no biomarkers to aging all the diseases are are there major risk factors aging. You know? So how do you define? And we basically did a lot of work and published a lot of work and showed that okay? Let's let's take somebody who has survived conser and he's sixty five to eight years old. What's his chances of getting cardiovascular disease, cognitive decline mortality ride the other things? And let's say it was ten. Okay. And okay now, let's switch around. Let's take somebody who had cardiovascular disease. What's his chance of getting concert in all the jesse's ten? Okay. Let's take somebody with outside world. He's johnson. Each really with ING it doesn't matter the disease. You get I depends on you know, your genetics and environment. If you have a mother who's diabetic and your bee's, you'll get their bts. I okay. But really because because we age biologically, you know, in different way, whatever it is the next disease, you're going to get the next disease, and we don't know what's the next disease. But that's what we're going to prevent that sort of. It's really interesting idea you proposed because it's in lending, you would call that asset value correlation. So you'd say, well, let's say near comes to my Bank, and he has a credit card, and he has car loan and as a student loan, and he has a mortgage any as a personal business loan, which one is going to default. I I don't know. I mean, I could sort of tell you typically people are going to stop paying their credit card before they stopped paying their car in their mortgage. But boy once you default on one those dominoes start to fall, very. Quickly. And so the so that would have what we would call it very high asset value correlation of the fault yet on sort of like this is the same for disease. Yeah. I think you're right. I'm saying into different. I'm saying I'm gonna stick to the zoo, which the first one is just I'm gonna stick. He doesn't matter. What you come? And what what you're going to have. I'm going to prevent whatever it is. That's why we have a complete. Okay. Compass and people get very prickly about Compas. It outcomes vary, and I got I'm gonna get on my soapbox for minute here. Because this pisses me off to no end when people get all bent out of shape about how you can't have accomplished outcome. And this is the bias against aging, really. Because in the end, what matters is how long are you alive? And how long has your health span? Optimized, so I'm sorry for I made that Rantiss short as normally could normally that would be a ten minute rant. Well, that would be a ten minute rent for me too. Okay. Yeah. Ops. Absolutely. And this is where we get into trouble. Tell you what the other pieces, but we had our grant review that the NIH, and unfortunately, and as this inside any of the groups except NIAAA like his NCI weighing in on this. Yes, I'll tell you what we've done. I'll tell you what we've done in this in a second. Let me just make sure that I say that so a reviewers where not jars because everybody's involved and with fourteen centers. Okay. So everybody's involved. So the reviewers are from other place, and they just they just just a minute. You're saying that agent can be targeted and one draw. Can do it you're crazy? Okay. There is no such thing. Why don't you do three studies? One studies. Mid formed, cardiovascular one studies Mott forming concert one day, and we're saying no because what are we doing? We're trying to give aging indication soon. Suppose we just such an end to the way they think, and I I'm not saying that to be critical of them. Right. But they're in a silo. I know his if you come to NCI, how can you care about anything, but cancer, right? I know the silence really are really killers. But for us. So you say, well, let's do although studies, but for us we're cul collecting, the power is about to say the power analysis on that study is going to quadruple your budget will for what they for the site for the site for us. It's not only it's not only the budget. We don't want to stop this study. Let's say that we show in two years that we delay cardiovascular disease, it significant than stop the study. And they said no everybody now has to be a mid forming. But we wouldn't be able to show the FDA that if we are actually that where aging for us aging is the stop telling us diseases. We are going to have a cluster, and we're just going to delay the aging. So we'll get we'll get the health span extended by two three years. That's what we're trying to show you and the significance is the for the cluster not for the individual disease. If you to the visual disease, I need triple the budgets, and I'm not going to get to the FDA with indication for aging. So it seems to me that the biggest challenge here is not the funding. It's not the study design. It's the conceptual leap. It's it's a completely different paradigm of how we think about delaying death. Correct. Correct. Where where do you stand today? So tell you few things first of all we conceived. It I got my friends to what I call a prison French prison in Spain somewhere we were in Parador in the middle of nowhere in Spain for several days saying would we have to do in order to open the field for aging to allow us to get treatments, and we decided several thing but one of. Them is to go to go ahead with by the way, I'm saying French prison because the food was good. I was not Spain. And we started a nice started getting those people those clinical people together, and we started really sinking through for what he takes throw takes. We have these hallock Demi and wrote papers in order to say how we're thinking how're thing of cluster of diseases. How we're doing power calculations for targets aging and stuff like that. We really spend a lot of time with the best people. Now are France came to us instead just a minute. Your study seventy million dollars. If the national survey djing going to spend seventy million dollars that means this the national surveys, very small. It's just three percent of the budget. Although we are eighty percent of the diseases, right? Then we won't have money for the grants. And I said will what I'm going to do is two things. First of all half of the money's going to come from somewhere else. That's my association with a far where Stephen I are the scientific directors and. For a far I go the other half. So the forty thirty five million is already waste, and that's mostly philanthropic. Right. And then we went and the institutes and NCI should chip. And see. I n it'll be I I d k they didn't commit because I they have to see the review. Okay. Or they have to have the decision that he wants. I will tell you though, that the NCI director was a good friend of mine is waiting for team to come. You know, he he's like where staying so the NCI has committed it's basically which contingent commitments. Yeah. I just I just wanna say committed is rumored because they didn't have a budget yet and the granton come to them. But I know that they will give the money because their head is will do it. Yeah. So that's good to hear. So when realistically went as the soonest, you would begin enrolling for tame. You know, I'm waiting for something to know next week. And if next week goes, well, so I just wanna let you know that we have an alternative, they'll turn ity is non for profits. That the reason they haven't joined us is that they're charter is not to fund anything that the NIH funds. They want something riskier, of course. So if the NIH is not funding because they feel three ski those will fund so we can start anywhere. And it's the the answer is early twenty nineteen. Okay. We're we're basically all our centers are ready to go any centers fourteen. How many subjects three thousand age sixty five to eighty any limitation on KOMO abilities. No infect will. They are. There are lot of limitations were very inclusive. But but no, no existing diagnosis of cancer. No, unless they're cured. Okay. So you could be in remission, but you can't have active cancer, you use it hat canary prevention or primary have cardiovascular disease, you know, in the past. If you're if you're okay now, you could have mild cognitive impairment in low speed walk will be criteria. So in other words, we don't want the people like in my study will become centenarians because we're wasting. We're wasting time on them. We want people who we know are kind of in the midst of aging, and we know that it's never too late to target aging. And that's where we're sixty five years and up five years studied, and you're gonna randomize one to one or two one to one and the placebo versus what dose of metformin two grams of fifteen hundred. So, you know, the sa- first of all I should tell you that Merck company from Germany's giving us the placebo admit. Forming Reta drug is free. So when when you say, nobody's interested. It's true. It's generic but actually Merck has the worldwide license for mid forming. And they're actually giving supply to lots of studies because they kind of realize that this is good. And you think there's a difference between generic metformin and branded in terms of efficacy reason now, so they're really this kind of this isn't necessarily a creative to them because one can by metformin generically, anywhere. They're not going to make more money from giving us, the will, you know, I should say even now a lot of them at forming suppliers have higher sales and a lot of them are known that Betty, so this thing, which is which is bet for me because I don't want to many people to know that right? I want to do the study. I don't want and I don't I want. You'll have you know, I don't think hopefully, it won't impair your your recruiting and the power analysis. I mean, it's funny. Honestly near I would have guessed. But this is this speaks to the non linear and complexity of estimating power. You can't do it without the tables. I would have guessed you needed a bigger end than fifteen hundred age group, you are using eighty or ninety percent power ninety percent, but I should tell you look for every disease. We have almost thirty percent effect. And we we chose twenty two percent effect. Okay. For every disease where preliminary data for the say on it. So you lowered your threshold to call it twenty percent from thirty percent. And at ninety percent power. You've hopefully powered this, right? You've got buffer both on your our defects. And and again, we don't wanna stop this study early either for one fact, so we carefully thought about it. We ask for a grant for six years because we don't want to overdo it. Okay. So it might finish in four or six. But we have the flexibility to look at it any non US centers. They all you know, we decided to do only in the US because of communication, and because look outside of the US people came and said, you know, will fund tain, but how you know, they say after two years, we won't fund them. You know, it's very different because because if it's a center they need to be part of the power, and we cannot afford to lose them. So we you know, those and other consideration decided to stick with the United States. So let's go back to. What we really glossed over. But now I wanted I've into why do you believe at the cellular mechanistic level metformin is an anti aging drug. So let me take you through that in. I don't wanna say schematics away because we don't have the scheme here. But in a way that maybe I think will be easy to think. So I wanna start by saying that studies have shown that some of the facts of with forming, our AMP kindness and some of them are independent of MP kindness. Yesterday is important not for mitt forming. But I don't know which are the ones who are relevant more for aging. Okay. It's hard to know. And it'll get complicated in the second more so mid forming gets into the sale through a transporter that Skuld OC one guy. Okay. This transporter is not equally equaling every cells. So unlike fin forming that goes without the transporters affect everything Mott forming is peculiar in this way. But we have the preliminary data any binds to complex one in the mitral congre. Does that do so preferentially does it gain entry preferentially into the liver in humans only in the sense that there's a nice concentration of OC one in the liver, but not not bet. But it's not I don't think it's the top other organs have. So basically, it's more about OCT distribution, and expression, mavens and specificities more that I want I want mitt forming everywhere. Okay. I won't forming everywhere. And and I'll tell you how I kind of proved it so now mitt forming binds to complex wanting might congre. I'll tell you. Admit form in has some action at genetic action that are independent of the mitral Conrad. You can do it with what's called rose zero sales. You can you can deplete my country and see and measure things, and you can measure things even without my country. Okay. Again, doing need them. What type of EPA genetic changes to see in the row cell in keystone city -lation? Okay. So I cannot argues disconnect be important. It's not important for us at Forman. But it's important. If you wanna ask me are the mechanism at forming AMP defendant might've Conradi defendant as there's an H Dak property that we may not have even thought of before. Right. Okay. So he gets to the mytalk. Andrea. And in the might Qendra it basically changes ADP ADP ratio. And that's a lot of it is important in the liver. But not only to the extent that there is. An activation of Ampy kindness and near is there a demonstrable reduction in eighty two AD h in that cell when complex one is inhibited. Yes. Yeah. Absolutely. Those studies have been have been done. So there's a lot that's going through Ampy kindness. And I will tell you the downstream of M, P kindness. There is them Tor. Okay. Any depletes decrease Amtrak tippety increase, and there's a whole poss- way that will go to the pillars of aging. I ask David Sabatini. This question a month ago where he doesn't know the answer. But I'm hopeful that may be one of the post docs in his lab will start to figure this out. I'm very curious about what the dose equivalent is between. In terms of purely looking at the readout of 'em Tor in habituation. What is the dose two dose equivalent of metformin via AMP K versus Rapa directly. And I haven't I mean, David to know the answer, which tells me, nobody probably knows the answer. Right. Look, it's it's really difficult. I afford, for example, lots of the known AMP kind activties are on much higher doses of mid for me. Well, that's my point is can you clinically match them. And no because you you really don't know at the end how much mid forming easing the sill what we're doing. Now, we're doing isolated sales. In other words, we treated animals with forming, and we're taking is elated sales to just see the ability of of with formula individuals sales in amongst homogeneous tissues. Yeah. Like, we'll take pot sides sites and look at the very expression. Yeah. Right. So it's all kind of important question. But but the story still I'll tell you the story because at the end I'm going to answer you what he's doing for aging. Okay. And I don't want to rush this story because this is a great story you take your sweet time. So think about it in a scheme. You have the mid forming in the middle getting through the plasma membrane getting to the mitral congre. And on the left side. Let's say there's the Ampy kindness. Okay. Now in the right side of sorry. Just for the listener explain what AMP kind as does the high level. It's it's a hormone of what it's a hormone of nutrient deprivation, and therefore it tells the body to do what like when you don't eat for a day AM PK goes up. Why will? But it's also an exercise me medic pathway. Yes. That's what happens with exercise. Really? That's was the the hope of what the aim behind these doing. But it's. A nutrient sensing that these impart upstream of 'em Tor. Okay. But the other side of mid forming is what happens to the might to country of because in a way. And I hope I won't regret saying it here, but mitt formulas the weakside night. Okay. Look what cyanide acted at complex four. Right. But now, you just mean more broadly speaking heading the right eighteen Heeb it, so yeah, there's less arrests production, okay in then, there's less inflammation. And there's other things that's going just because it might country are his list of see the Tiv pathway going down. So this is a great example of why binary thinking doesn't very doesn't do very well in biology, right? It can't be all or none will. So now, I can go on and on and connect, although sweet due to eventually. A pillar of a, gene. But I wanna insert another thing because other things are happening, for example, insulin levels goes down. Right. Why is it just due to the reduction of paddock Lukasz output? I'll tell you why I think and then also inflammatory factors are going down. And there's a whole NF Cup be action of mid forming that might be part of the hour s and part could be independent even without my congre. Okay. It's confusing. But this is the point I wanna make I don't know which one of those is important for aging, but parts of what you're measuring is the following yueh-fei the aging on a cellular level. Okay. So the younger that the sales are younger a lot of things are correcting themselves. So I think at the end the lower insulin levels low inflammatory are not necessarily direct effect. And that's why we're we're fighting all the time a buck multiform these doing because you can measure lots of things, but the things you're measuring because aging was fixed and once agents fixed, then there's whole Hemel dynamic readjusted, or whatever you wanna call eat. And then you're measuring that everything, and this is not only typical mid form this with rapamycin with veritable. You also can see that. There's a lot of things that are improving themselves. And I think we have to get used to the FEC that when you have a drug that we argue what it's doing because everybody's measuring something some of it is true. But it's like secondary. It's you fixed it richer, and unrelated, and it's funny. You mention those three which again, I think speaks to an advantage you have with tame. So when you look at rapamycin, reservoir, trawl and metformin the big advantage of metformin. Is you already know the dose and the frequency with rapamycin over dinner tonight. I'm gonna give you my philosophy on the dose and the frequency than we can discuss it. But I can't demonstrate it to you with anywhere near the validity that you could do the same with metformin at wonderful discussion with David Sinclair and bioavailability came up on resveratrol. Right. So maybe all the trials that say resveratrol is meaningless are simply not looking at what happens if you get enough Rivera. While in the right place. And again, I it's amazing to me. How many times in biology we can make mistakes of the first order because of third or fourth order omission, and this I guess I I don't think I realized that until you just gave that explanation. The value of. Effectively millions of patient year's worth of data on metformin, not just from a safety standpoint. By the way, liens it's billions billions. Yeah. So billions of patient your data on metformin. I know that from an FDA standpoint the highest priority is safety. That's a low bar across the more. Interesting one from the standpoint of this study is actual efficacy. Right. And it seems like if I'm hearing you correctly metformin is an amazing be student. Let's not be insulted by that. What do I mean are there better ways to inhibit Ross? If you wanna hammer the Ross chain, probably there's clearly better ways to inhibitory. That's all you wanna do are there better ways to modulate h Dak. Yes, I'm sure there are, but it might be that maybe part of metformin xvbeauty is. It does so many things at a B plus level. Never. It's an ace student, but it's not a D student, and it's never, you know. I mean, I'm sort of thinking about this sort of a tongue in cheek way. But it's it. Seems to do so many things reasonably well will I call it formula tool from my perspective is just a tool to show that we can target aging because I think that there will be much better drugs and communication drugs and other in the future human lifespan is one hundred fifteen years, we argue maximum life. Yeah. Moxie is. We argue because there's somebody hundred twenty two, but there's this these things so okay, we die before they Jove eighty. So there are thirty five years that is a species without not that we cannot change more. But just now without thinking too much futuristic law hanging fruit that we can do and mid formula the perfect tool to start showing the proof of principle here. But the future is much better. It's just you have to to pave the road here. This is a beautiful pivot to something else. I want to discuss with you. Because unfortunately, I could talk about metformin for three hours. But there's so many other things I want to discuss with you near based on your work, and you just alluded to one which is the work that you and your colleagues have done on centenarians has been very influential in my thinking, so as I think about aging clinically I ask the question start with the existence principle. What does it mean to live a long life? Is there proof of this having existed? And there is we have centenarians they exist. My hypothesis when I first started reading your literature, which was only about five years ago. My hope should say not my hypothesis. My hope was that whatever genetic benefit they had which it became very clear to me very quickly that this wasn't about what they did. In fact, they seem to have almost near immunity to the worst behaviors imaginable, my fear. When I read your first paper, which was a review paper. I can still see it. And I still remember where I was sitting in Sheridan hotel reading it. My fear was whatever blessing. They had it was it had nothing to do with chronic disease, and it had to do with something nebulous, and they had complete immunity from chronic disease. And they just died in car accidents. Like, they eventually just died because something else trip them up, and what I took away from your work was no their genetic gift was a phase shift and when they got chronic diseases. They still died of heart disease. They still died of cancer. They still have Alzheimer's disease. They simply got twenty year bonus if not more maybe twenty nine on average, you could calculate call. It a close to thirty year bonus of hence spin. Yes. Yes. Because completely functional they hit compression of merb'ys. So it's not only that they leave a longer and they lead healthier, but they died died quicker quicker than not. And you know, it's interesting the CDC. The center for disease control have looked at the last two years cost of life of people with different stuff. So they looked at people who died at seventy and after hundred and the cost of dying after hundred was third of that of dying in seventy. So it's not only in our study. There's actually evidence law didn't know that to suggest that the medical by the way, those when they were seventy they didn't go to the doctor. Okay. So the and this is the base of this concept skull Dylan jetty dividends. Okay. What what will happen to society will actually be healthier for two years and the benefits are immense? You think only of the, you know, so we pay social security more and stuff, but they're seven trillions dollars just in saving of medical costs. If you could just leave healthier. So I know you don't spend an enormous amount of time anymore thinking about the centenarians, you know, your literature. Followed very closely. You you definitely are spending much more time talking about and writing about the things that we just discussed. But if you could go back in time a little bit for me, by the way, that's true. Maybe it's just selectively where I'm reading. Well, no, I think that's what's interesting to people now. And I'm very happy about it. But I just got the, you know, the jetty apes and longevity price in my talk was actually about centenarians with a little bit of my hypothalamus stuff that was related to something. But the centenarians are, and we have lots of grants on the centenarians because you know, this that talk by the way of is something that people can watch. No now, it wasn't. There wasn't record on to shame. It's real. I thought about about the stock. It was fun for me to give because it was reflective a little bit. You know, one of the things that's always funny for me as people say, oh, you know, I have I can measure these thing. I'm sure that centenarians they have they have high level because high levels are good and I hit. To put into rest, the fact that the genetics of centenarians is really great for me. But the fennel type is not because you have a hundred years old, and you can measure something that can reflect what brought him here or the fact that thirty percent of them are going to die in the next year. So it could be a marker of of this and not of longevity. Either fennel type makes doesn't interest to me. That's why I have their offspring was their offspring will have the fennel diaper a half of their altering. We'll have the fennel time. But those things were something that was nice because so many people saying, we should measure sincere note. We are we're doing longitudinal study on their offspring and their offspring are equal everywhere to our control group. They just have half of the diseases, although you buy that it's really interesting point near. I never once thought of that. I never what you just said that if I have a hundred year old centenarian in my study and. He or she has a C tap mutation or an ABC three mutation. I look at the predictable FINA type because I know what you should have. If you have that mutation hypothetic shinning ABC three should have low triglycerides, but technically without a little more longitude in legwork. I don't actually know if what I measure the result of that. But that said there must still be some benefit in. You know what? Now that I'm saying I realize you can't do it. The dream state would be to have health records and phenotype for centenarians that go thirty years back. In other words, it would be beautiful to follow a centenarian from seventy two hundred so within a typic-. So that's why we have the Janati study. It's a longitudinal study of auspice of centenarians and people without longevity. And we're going forward. We're already ten years into the study. And we're starting to see the differences between those guys it's different population. They're aging slower. Okay. The children of scenarios. So we have some of these things in mind, what are the most important genetic differences between those either centenarians are offspring of centenarians and the rest of us. So it's very interesting. And so this is a part that you haven't hurt. So from. But it's actually the growth Ramon idea. Faxes we have probably sixty percent of our centenarians have genomic reasons to let's explain the normal path about. So the patera gland makes G H. It tells the liver primarily to make idea right bind store receptor right in the liver. And I g f and so some of the facts of the growth hormone system are through growth hormone itself and some of the is through. One level both of them are decreasing with aging. So in this system, we identify more than sixty percent. And I think I'm underestimating. Okay. It's more. It's probably more, but I didn't really calculate who has several mutations. I can calculate how many mutation they are. But the overlap of them you take action. So I'm I'm saying sixty percent, but it's the most common genomic alteration in our centenarians. And I have to ten where is it? Specifically. I'll tell you a second. I wanted just to tell you I never I wrote grandson that because I thought because there's preliminary data in nature the small dogs live longer. Yes. In the Tonys live longer, and when you mutate rose Ramon or or they're born dwarf they live longer, and when you give more growth hormone leaf shorter. So there is a lot in nature, but the human data was really confusing. Some diseases. You know, when you have if you have more concerts, but you have less Alzheimer's cancer. I'm sorry, less heart disease, unless diabetes, but more cancer, right? And mortality in mortality. It's like in the middle. You know, a little bit tending to more from you know, from concerts by our analysis, which I think pulls all of your data. We found that there is in a U-shaped mortality curve with the Nater being between sixtieth and eightieth percentile of all cause mortality. So I wanna tell you the problem with this association on one hand and individual h quickly. Okay. Their growth hormone. I if goes down quick. Okay. So you would measure falsely low I just one level if you bet on the wrong side of their aging that wouldn't feet are theory that low I Jeff is good because that's their their excel A-Rated age. Yeah. So this is the problem with an association study like that way discovered. First of all that when we take our Cincinnati. So they're they're in our study because they've been healthy at age ninety five leaving independently we take them at any age. But that's what they have to do. And we just look at those with highest idea from the lowest idea one level those with the lowest idea one level leaf twice as long those are already two centenarians. But only women men do not an every example that I gave you there's a sex difference. The grows IGF is very sensitive for women. Or for females are near let me ask you another question. It's very difficult clinically to measure G H because it's pulsa tile. Right. So whenever you're saying growth hormone, are you really saying I g f which is easier to measure. No because I'm going to talk soon it but not on what the measuring. But where the mutations are. Okay. Okay. Pete. What you just said the difference between men and women was that based on Jeff level or G H left eye level. Okay. But we discovered in aging we did the yield full PA. Okay. That we are. Now correcting we we studied in in our labs males only with excuses females are menstruating. We don't know their effects, and we're all discovering look even Rupp amazing that really works everywhere is bettering females than males. But is in males right there there examples where we totally missed the sex effect. And growth over Niger is a perfect example, except those mice that are the snail Mayes or the aims miles. They have Baotou etry problem, which makes them I think sex confuse. So you know, they've so many other interational but sex differences important. We also showed that those women with the lowest idea one level has much less cognitive problems. You know, third of the cognitive deficiencies of those were the highest idea if all right, okay? So we had to grab our second round of topa Chico there, which by the way, I didn't even ask you front. This is your first time having to Pacheco, right? Yeah. I'm in love. I mean, this is there are few things that bring me as much joy as introducing people to this bottled water that period has is much. Milder I like to feel the the bubbles while I would I think one thing we should consider for tame is if we can have an arm that also includes. Topa chico. So there's a placebo there's a metformin. And then there's a metformin plus Pacheco in that question that hypothesis will be does that somehow enhanced lifespan because even if it does not I predict it will enhance happiness. Well, I have to tell you. I'm an advisor to the prime minister of Singapore. Singapore's plays the plan the the future and before going said, why don't you ask me questions in one of the questions, shall we put mitt forming in the woods erring sodas now. Good to us. The answer is no, obviously. But it's good that you're thinking that way. So mitt formula. And should you change your mind? I think you now know which soda it into. Can you get it in Singapore? I'm sure we can. Yeah. So back to sort of what you were saying this, this GIF, male female disconnect. Let's let's keep going down that rabbit hole. So I was saying that one of the worries about low growth hormone idea is affect on the muscle because people think that growth hormone effects muscle function muscle size. And we found that in females and males. The one level is not associated with better worse. Lots of muscle function, including grief and getting out of Charon, you know, other things. So maybe the -ffective Loide Jeff an aging are just as good as having higher fictive idea on muscle just ways it self out. Okay. But then our studies genetics. Okay. That's what we tried to do. And. Several years ago, almost I guess a decade ago, we found clusters of mutations in the. Jeff receptor those were new mutations that haven't been found before. But we found him in nine of our Cincinnati, which was two percent of our centenarians. And that was kind of a proof of concept for us. That that clusters of mutations that are functional is what we really need to look for rather than like, everybody's doing doing Jewess and find, you know, something introducing somewhere, and this was also the first proof of concept, the growth hormone, I could be relevant to Uman human aging people that those two percent of our those nine people head higher one level because they were resistant, right? It's Jeff receptors. They're resistant to I Jeff so their level was a little bit tire. But they were significantly shorter than others. Which is a great explanation of how that FINA type would play out. You would say, well, how can they be short-statured with? Hi, Jeff, and the answer is if the isn't as affected at the receptor, right? But remember that most of our people with low idea for doing better, by the way, we take the people with. Is right men men also or just women to manning those nine people, and by the way, then they're dwarfs human dwarf that called Laurent dwarfs the evening in Ecuador and hussy coin in Volta Longo in some of the people in Ecuador were looking basically, we're trying to find if they leave longer too few of them to really know, but they have less concert unless they BT's, you know, significantly less. So there's other evidence from humans came after hours that that there is a least less age related diseases. Those people certainly didn't live better life in any way that we could assess corroborate. I mean, we we always joke that. They they weren't happy with the -ffected. They're short. So they drank a lot and that's out collegium. And then when they cross the road, nobody so them, so they're died more trauma. The, but I think it's really not true. So I met some of them we were in the conference. Everybody has to to bring his Beijing Longo brought somebody from Ecuador in. I brought a centenarian from Rome. And and the guy the T bro told the different story wasn't unhappy. It was also heavily married with a big woman and had children and with the so I I don't is the defect in them at the growth hormone receptor in the liver in the league. So they make normal amount of growth hormone their liver. Doesn't acknowledge I amount of growth hormone jackals. Yeah. Yes, they have lots of growth hormone. But it's not being expressed through the liver into I. And so they have no idea. A so. We published last year paper that took us ten years to write basically, we were looking at a relatively common mutation. I'm saying common because it's like three four percent in the population where they have a completely tion of XM three in the growth hormone receptor. Okay. So one of the Exxon's the, you know, one of the things that are important for the integrity of this hormone right is the league. And of course, you would think that that means that the growth hormone is less effective and Gillet Smail was fellow with me brought me this data to suggest that while it's three four percent in our control population. It's twelve percent in our centenarians. So I asked so what's the idea one level, and he showed it slower. And I said what's the height of the people? He said, well, that's the problem. They're much taller. So I said, I cannot do anything with this study just makes no sense. I don't know how to write to them people with lower idea. But the mutation was in the Exxon of the girls from on receptor, so they had lower Jeff five, oh this function of the receptor theory. So less idea, and we know that it was fully penetrated all their life. In other words, we there's no chance that it didn't start showing up until they were in adult WALE. Will come back to that. But the mutation didn't change and by the way, just give me some numbers here. How lower the ri-. Jeff's. I don't wreck Tionling. We're talking about like less than a hundred or less than two hundred. Okay. Yeah. Hundred is about the median level of GIF for somebody over sixty five. Yeah. I think in the studies that I told you the everage or the Nino whatever was ninety four something like that. I don't remember to answer about those people. Okay now. Okay. So he said what to do? I said well, first of all what you do genetics. Do replicated study. You know, you go to other populations. And you see what's going on there and second you do a functional study. Let's see if it's really a functional mutation so it took almost ten years. Right. And in ten years, we replicate the data in three other population in Amish French centenarians in the. The siege s here in the United States. And in all studies that people leave the longest head much more of those. Komo's I go cities in the growth hormone receptor. So that was a great validation second, the functional so hussy coin might might partnering UC we send him the lymph oblast of our patients affected, the not defect it than he is a growth hormone idea expert. So he incubated them Serem free. So without stimulation and with growth hormone and looked boated activation and proliferation by growth hormone so in Serra free without stimulation. They had less active, Asian and less proliferation. Huff of normal suggesting. Yeah, that's the mutation. That's the function when he incubated them with gross Ramon. It totally switched. I'm sorry. Going back. You talked about. Proliferation. But was there a functional difference in the lymphocyte in addition to its increase number? There's yet the the I was activated by in some of the okay some of the nonspecific activation. No, no specific to what growth Ramona's doing. But it really ration-. It's you know, that's an easy one. Yeah. When he incubated with gross money. It was the opposite. Rather than the slow proliferation. Low activation was high active Asian high proliferation. So what's going on with what's going on? When do we have high growth, months Repubic? So with high gross Ramon something has changed in declaration from log division jump to high evasion for reason with the Malacca the real mechanism. We don't know really. But that's what happened when you have high growth hormone. So they all were Toler, and then when growth hormone go down for the rest of their life. They shut off. Okay. So so, okay. So this is twelve percent of our people then Yutian sued who's a geneticist that's working on this. She was interesting micro Rene. That's another EPA genetic thing. That's comes we we haven't been thinking about. But those are our that comes from certain region of the gene and they bummed bind specifically to active region of the, gene. And they multi late will thirty percent of our sentiments have clusters of micro Rene that are over expressed by lot by forty times. You know, just immensely activated. One of them, for example, Micron ary Micronesia one forty two that's increased by thirty five fold when you incubated with with sales. It prevents the facilitation of the idea receptor. Decreases, some other singling fuck signaling and some other stuff dramatically. So there's a micro Aurigny targeting of the growth hormone idea for sceptre in about thirty percent of our centenarians, then twenty two percent of our centenarians mutation in folks three that Sukumar new tation in centenarians. So you start to percent and twelve present tell people at FOX three does folks folks are three A is another holiday say just house. How stays? Yeah. Housekeeper that lets in good stuff in change things in things in stop. It's too complicated to go more. But it is part of the Terim insulin actor at at regulating Hamis, sailor harmonizes, and that's not a great explanation. But yeah. It isn't FOX the most prevalent genetic difference between if you were to just isolate them by by Gina type, if you look at C Tappin C three and FOX, oh and g h and I Jeff I mean, if my recollection is that FOX might be the single most prevalent of folk so a mature through with FOX's three A is common in all centenarians population around the world. Not every population has the same you Teychenne's. In fact, what we're doing? Now, when we have the XM sequencing of all are subject, you know, almost three thousand XM sequencing, the important thing to do is to assign them to pathways because you know, we're doing something really silly with genetics. When when we had these Jesus, we we said we have meaning snips around the genome, we'll find diseases every disease in the world. And one of the stupidest thing we did we took one sleep at the time. Okay. Let's see this nip is significant, but we're not build of Swansea of time and certain population. There is down that down despotic there'll be another sneak that will change the function. So you need unique to our analyses now is totally different than how we started. But this, you know, I agree with you completely. But I don't think most of the world is listening near. I mean, if I had a dollar for every time one of my patients. Came with their, you know, complete sequence. And you know, they want me to interpret them. I have the same discussion so many times. Okay. You have twenty thousand genes to my last counting may be seventy eight of them have deterministic relationship with disease. You have none of them. And we know you have none of them because if you had any of them, we would know by now, there's no chance you got here with the Huntington's disease, and we sort of missed it. Or there's no chance you have some inborn error of metabolism that somehow got missed and then we get into this whole g waas morass. And you know, it's hard to explain to people. How multifactorial these issues are. And I find myself, maybe you do as well somewhat frustrated by these discussions and the over emphasis on this genetic, you know, it's a little bit of the drunken the streetlight problem. Right. When the guy standing with other street, light, and you. Say what are you doing here? And he says I'm looking for my keys, and you say did you drop them here? And he says, no. But this is where the light is. So let me not increase the complexity but give you another munition. Okay. So we did, you know now several years ago because of funding we did our forty four best, you know, first centenary ans their whole genome sequencing so think about it. We have a study without control richest have forty four centenarians, and we do the whole genome sequencing and our question was do cinemanow have this perfect genome. I mean, maybe one out of ten thousand they just don't have all these crap from the genus those snips for hearten out severance of they're just great. And we went to this data set that Skuld clean VAR clean VAR, then head the fifteen thousand but to genyk mutation that most probably will cause a disease. Okay. Now, they have about thirty thousand. And our policies that are Cincinnati's. Don't have any of those okay. Will support the perfect. Forty four centenarians head more than two hundred thirty mutations between them another five to six mutations. The shoot have caused them diseases, and none of them had this disease in hundred years of life, and some of those mutation I'll give you the best example for Parkinson and conser and everything but Upul e four what's the in? We have to up four hundred years old people that the textbook would say they're demented at seventy dead at eighty and they're not demented. The no dead at hunter. You think this at all explains the LPGA uptick, we see because, you know, one of my favorite topics lipid, Allah g and of course, L P little a is a very variant Leiper protein, and yet centenarian seemed to have more of it than the general population act. So we actually we actually showed in a in a paper because we. The we we found a way. So basically. A week, obviously, we can have mutations that are protected because they have slow aging or longevity genes. Protect right. So how do you prove it? So we noticed that when you look cross-sectional. I hope I can make it very simply when when we put any genotype cross-section Louis. In other words, we have all ages from fifty two hundred twelve is our oldest. We see patterns if we see pattern that the general type is declining with age. We know it's killing people. Okay. If we see that it's kind of monotone eclipse increase with age like with concentrating with yet. Then means the people are surviving are surviving with this mutation. That's why we have Maureen on rid like the example of Roman receptor going for three to twelve. In Montana Kway. So we looked at L P lay. Exactly. And this is the most confusing of them all because I don't see any compelling evidence. That LP little a is anything other than Athar genyk. And so it begs the question, why would it concentrate in centenarians as opposed to just rise commensurate with the population? Exactly. So this is the Unser. Okay. I the all we shall cross-sectional that LP drops until the age of eighty by half. In other words, highly like crazy until it's not right? And then and then you look at it, and you kind of try to send just a minute. Now. This thing that killed now. All of a sudden centenarians have even more it should stay flat after these right? It should be fled wise, it increasing. Will because it's a protected aging, gene. In other words, it was obviously during evolutionary times, are you saying that the the thing that LP lay did for us five hundred thousand years ago that is no longer beneficial in his lousy environment. The centenarians have managed to tap into its properties of. No, no. So what we did what we did in. It's all published in computerization biology journals, we took everyone of longevity, gene that we have. And we did gene to gene interaction. In other words, we try to see if there's interaction between the bed genotype and the good genita- good longevity genotype, and we didn't to variety of those U-shaped, right? I'm I'm telling you, there's a U shape. Don't always goes down with aging. And then it's good incentive. And we really found statistically significant that L pill is protected by people are homeless ideas to a CT mutation that these on Jebediah mutation that we we found that's the av mutation v mutation in other words, most of the people with the L P lay that are centenarians were also CTP CTP Buteau. Can we tell people what that phenotype is? So I've talked on his podcast a lot about see tap and its role in reverse cholesterol, transport cetera. Talked me about what what does the lipid panel like for someone who is v plus or minus LP little so those would C P V they have higher HDL levels. They have larger life approaching particle size, and they have lower CTP levels. That's their fennel type. In this city has is being protective against several age related disease. The most dramatic is cognitive decline. And by the way, the two upper four are also CPV carriers. So really the question is sounds to me like if you are seatac v that's a very protective phenotype and the difference. If I remember the day that going from seventy to eighty was basically flat. If you're seatac v it really goes up when you turn eighty meaning the concentration of seatac v the genotype, yes, gene type goes up significantly. Once you had eighty it goes in fifty five it's eight percent of the population and at a hundred twenty percent of the population. So it's also important to know that not first of all the eight percent attentive. Vivey? I don't know how many of them will be centenarians. Right. And also not also dinar v. But it's a really it still very impressive. Because the problem with HD L cholesterol is just such a dumb ass metric, it's so useless. It's so far downstream that it doesn't tell us much. But the hypothesis here would have to be that these people have far more functional HDL particles because I mean, we don't have to rehash this. But anytime you've pharmacologically increase HDL cholesterol by inhibiting, seatac nothing. Good seems to happen, right? Because you're actually impairing your ears. Transport right. So he tests to be with fix, right? That's why it has to be functional functional thing of the jail, probably or the Leiper protein particle side or something. So I understand all of that. Here's the part. I still don't understand near. Why wouldn't the LP little a phenotype or the L P A Jean flatlined after eighty in other words, I understand why see tap Vivey is protective. I don't understand why L P lay should concentrate. I think because the CTP is common and he's very protective. And that's why you do look. It's a cross sectional. Okay. By the way. It's a good question. That's what we ask whites not fled. But for a person who's born and is going to be a centenarian for them. It's really not. So so they don't die women. I I need to do the math. We could do this over dinner will sketch this out on. App. Can you take a hundred people who are going to be centenarians one hundred people who are not eight percent of each of them. Call it ten percent of each of them have L PA. We should do the math on. If it's are we being fooled by the age because I do have one alternative hypothesis, by the way, I'll show you out show dinner. I'll show you the actual collect computation. Okay. So so this'll be good. This answer my question because the other hypothesis I've often wondered is depending on Sol start with my question. And then I'll go to my hypothesis how much FINA typing have you done on the L P A. Do you know how much heterogeneity is with their kringle repeats, for example? Now, I and I don't have their LP level. I have just their LP genotype. So this things that we've done our though, we can do actually we've done a little beat on the CTP levels or we've done but those calculation are on gene to gene interest. Okay. Taking out the people without genotype with genotype. And seeing who are the people were the centenarians it stayed with the bed LP genotype. They're only the ones where CTP also I see do you have serum stored on these subjects? Yeah. But but an I have proteome IX done in. Maybe we can have some measurement of not sure I wonder if there's a clue to a very vexing question, which is why is it that some people with high L P little a do not go onto get premature heart disease. Many do most do a significant number do not, and it appears completely uncoupled from the level of their L P little which makes me wonder are their virulent and non virulent FINA types that at the level of expression by number or molecular weight aren't captured. And my question, then becomes is. As the non virulent one the one that is concentrating in the centenarians. And are they the population in which we should understand that phenotype? So we can better risk stratified the rest of us leapt walking around today. Ten percent of whom have elevated L P lay. But we don't know how aggressively to treat them. Yeah. I didn't know that. There's Vera Lynn or non elp. Yele? My explanation is totally gene to gene direction. In other words, you'd do another fennel type, I guess the Unser is different is that the people with what's the LP little a what's their CTP level? What's their HDL? What's their age jail particle size? And may be you can see it's generalized that if you he would see P L Pillay has less the problem. We I agree with what you're saying the challenges we do not have HDL functional ASA. So right now, we can measure shell cholesterol, we can measure h particle number and we can measure jail size. But none of those come close to. Telling us how functional departmental I have collaboration with den Reiter. Yep. Who's doing daily flux and stuff Dan is a God in this field. Yeah. So maybe you know, that's not my this is poss- life for me. I moved on. So I I don't really know to answer you. I I didn't really let's go back to the idea h thing because this one still creates tremendous let's bring it back to clinical stuff. So I'm often asked by patients. Hey, should I be on growth hormone? And my answer is I don't think so. But if I'm going to be brutally honest. I really don't know. I really have no insight into whether growth hormone is exaggerated ministered, growth hormone is harmful helpful neutral, or what because the clinical data certainly don't give us the answer. Right. So the epidemiology if you're in sort of vaulters camp is that would be the worst thing you could ever do growth hormone is bad because I Jeff is bad. But again, the Tele different. Story. Tell a much more nuanced story that has to do with how high is too high at what age and for what gender and with respect to what disease. Of course. How can you manipulate idea full? You can manipulate the two easiest ways to manipulate Jeff the three easiest ways to manipulate idea for to manipulate growth hormone exaggeratedly manipulate idea dietary predominantly through me, no acids and manipulate insulin to indirectly impair or enhance Jeff binding proteins letting T we just published a paper nature months ago study that we're we're going also for a while in what we did is. We got from 'em jn engine is much as other pharmacies tried to develop antibodies against Jeff receptor because I just receptor is expressed in many concerts. Yeah. This was the disaster drug that they tested against metastatic, pancreatic cancer and failed. But if I recall the very special little gift. Which is no CNS penetration might think of the right one. Yeah. Right. So it failed, but we're interested for aging. Yes. And not only were interested for aging. Our policies was that. I if you know that you need to decrease actioning, the periphery, but increasing the brain because of the data. So we asked them to more Anais their antibodies more is means to make it available for a mouse. Right. And we got an we did alone. Jetty studied that we started the twenty two months, whether they remind me in the human study how much did it lower. Jeff in the periphery, it increased. I'm sorry. I know I'm sorry. How much lower activity in the privilege was at a reduction by what fold like was it a twofold reduction, it's very hard to measure, you don't measure it like that you measure it in in, you know, in vitro, it's very hard to measure how much dot and they re. Rebounded a little bit with Egypt, which is not the case with aging because with aging you don't have the growth hormone secretion. So we gave it to twenty two months old animals that are seventy seventy five years of age equivalent, Wayne, Chris their health spend, dramatically and wing Chris their lifespan by ten percent. It's an old age. Okay. So this is a drug. That's already was you're able to demonstrate I'm sorry. I missed this paper came out a month ago. So I'll be inhaling it the this time tomorrow, you basically showed that you didn't change IDE Jeff levels in the brain. Or you actually increased Jeff levels. We we really don't know there is a little increase in Nigeria one level in the periphery. And we're assuming that we didn't make it a big I'm telling you what we thought we didn't make it such a big deal. But obviously the unto bodies do not cross the blood brain barrier. But the I wasn't lower anything was high. Right. So if anything. Jeff went up in the periphery because it was being blocked and therefore a little more into. So you could have had more CNS activity less peripheral activity not now again, those were aging, by the way it was in females in males. We started to do the studies in males. And since we didn't see any major facts, and we had relatively little, you know, those are months of studies in many mice. So eventually did the longevity on lean females? We don't have data males. But the extent of health spending you you'll see the paper. It's really it's a great bay with lots of studies, and it's impressive. How much they debater the famous with it. So there you have an example, we have all the possible you ask what do we do here is it's been in humans. Okay. The idea for Johnny buddies. They're the only problem for us is aging could be an indication what what's before aging like we need another indication in order to. Stuff selling before. But what's your hypothesis in those mice in the female, mice that they you said they live ten percent longer and watch healthier much healthier. So they had compressed morbidity as a car. Do you know they had to cardiovascular protection, they have cognitive advantage functional adventures the whole thing the interesting thing between male and female, the difference is the mice the female Mayes that were treated with Jif receptor onto body head a lot of of inflammatory markers. Right. When we started. They were twenty two months and those inflammatory markers were really decrease with ageing in males. We hit a little bit more inflammatory markers. But they increased with the idea if treatment so may be the fact and both the males in the females had an increase in peripheral IGF, presumably the antibody working in. Both of right, but somehow the inflammatory response in males was different. So it's all driven. So I'm on Seraing YouTube things first of all what do you do? Here's a good example of drug that was in females and we have preclinical proof of concept that it's good. But the second is in males. Although have not been shown ending fact, you know, the functional they told functionally women it looks like the function was better for man with a hierachy if and not with lower not statistically significant. But you could see that it might happen. So I'm telling you from human studies from genetic studies, I'm telling you grows. Vermont treatment is not been official ID should be dangerous for elderly people for elderly women with men amorally to say that. I'm not sure, you know, I'm not sure it's not the type shown that low idea. Gross. Ramon is bettering males. Nothing. My a rodent studies and not my Uman studies. But it's hard to say that giving growth hormone is bed. When you know by the growth hormone receptor story is a lot of them are males that re- that this this is so interesting. I mean, this is such a a layer of sophistication to this question, which I I've largely sort of decided that there can't come up with a compelling reason for executives growth hormone. But I also can't see much evidence clinically that. It's killing people. But of course, I think disproportionately the data are in men. What do you think explains this sex difference between men and women I think unreal? If you look at these inflammatory panel, lots of cytokines. Lots of animals, I'm not sure we don't have the intellectual link to say what happens. But this is something we want to actually go on an exam. Because if for some per doc sickle way that these sex dependent low idea, if increasing FLA Mason, a we wanna do we wanna know why? And we wanna know how we can affect it. Right. If you could repeat the study with younger, mice, both male and female again because I mean, the most obvious example is the biggest difference between the men and women of the sex hormones and the older they get that difference is still there. I mean, women will female mice would go from having some testosterone two zero testosterone. But gosh, the men would probably still have more estrogen than though, the males have more strident than the females post menopause, right? Which makes me wonder if the estrogen progesterone testosterone are somehow predict a protective of the inflammatory effect. So there is a, you know, we're working on a grant because the sex issue. So interesting, we we started working on their lots of models where you can change x and y chromosomes and stuff like that. And you know, we're looking at the way. To look at the because it's I don't think it's usually a simple as the sex hormones. You know, I think we're missing whole by g it hold biology, and whatever is the sex hormones. I don't understand the inflammation in that either. But by the way, your ideal doing it young is good 'em sold. This idea of receptor. We we cannot get we cannot get more some pills. But we're interested to maybe do our own with Amgen sold the rights to the human antibody. Right. Their whole section actually their whole section to which company owns now to like, a private company that we're unable to get people to though I have to say, it's not our major priority now, but in and we have some consultants that are trying to get together with those people. So you know, it sealanes you, but I'll tell you if I had to develop a treatment. I would rather use the micro Rene one forty two because. Because the I receptor antibody didn't working Concer, but maybe the micro Rene penetrates better in another way. And maybe that's the way to decrease idea if receptor in you know, in concert, so anyhow, but a really unsubdued that. Yeah, we there things that we could do to affect the pathway. I mean, what do you think about sort of all the to me the most obvious way to manipulate Jeff is through fasting? So about once a quarter. I fast for a week with just water only, and it has a profound impact on my Jeff level. So for my age, I think I should know these numbers off by heart. But plus or minus two standard deviations of idea for my age is about ninety two to fifty. And if I take my if I measure my Jeff level before fast right before a fast, it might be one hundred eighty two two hundred and right after. After the fast, it's eighty or ninety and six weeks later. It's maybe one forty one fifty so it sort of falls precipitously during the fast, and then slowly rises and then falls precipitation slowly rises. And there's part of me that just wonders if a cyclic approach to issue is a healthier approach than say constituency being caloric restricted and just you know, because you can starve yourself of methionine and eat no protein and live at a lower Jeff level of maybe one hundred ten forever. But I wonder if the the real game is sort of figuring out this sort of cycle and periods of just just as we think of tough Aji, if you're always in state of tougher, gee, that's a bad thing. If you never have a toughie, that's a bad thing. So, you know, about the calorie or the caloric restriction that the NIH funded in three centers. Yeah. Eric Rava center, cutting son was one of the main PI's, why does things is that idea level wasn't crease. In those people, right? And we think decrease is really important part of of longevity. But we we've we learned something else. Maybe I'm digressing because I'm sure you're talked about more that what we're doing in Retz wasn't really caloric restriction. We're doing intermittent fasting because in our rodents. We would bring the food in the morning. They were hungry grind. They would eat all the food. You know, the sixty percent whatever we gave to libido, and they're fussing for twenty three hours, and and they had low, you know, low I one level, but the Eric revolt studies that didn't have low. I because it wasn't caloric restriction like that. They gave them just less foot throughout the day. Okay. And I, and I think that was a big mistake that we realize that we were doing and he doesn't answer this. They're circulating. I think what we're trying to find Stein is we're doing a study, we know that. Autophagy is improved quite fast in fasting rodents. We don't know the time line for Uman's. Okay. So we're trying to figure it out. And by the way, we can do without ah Maria Cuervo, we can take t lymphocytes and look at the tough Aji on a time course in Uman's, and they actually reflect also tougher in the brain there. There's a lot of advantage in doing. What are you looking at specifically in the ASA? Will there are several things because there are several tougher Ogies. Right. So Microsoft Aji or or chaperone mediated tougher g so there there are several things that you measure, my Taiji also. Yeah, we can do we do that. Yeah. How sensitive is it to meal timing? You know, like, for example, if a rodent is fasting for twenty four hours, especially a mouse. I mean, that's gosh. That's probably the equivalent of human fasting for a week. Presumably Tafa G is. Highly highly highly up, regulated if you give them out a little bit of Chow, and then measure that essay does it obvious Kate does it does it race. The fact that they've been does it create the allusion I guess I should say that it's a race. But they've had this high period of tough, did you transient truncated, you know, unequivocally than I don't know the answer. I I don't know the time course, and but the important thing is to find the time course in humans. So that we can really say, for example. I'm what I'm doing. Basically is I'm trying not to it after dinner until like lunchtime the next day. So, but do you really I mean, so I know how hard is it to get an IRA at Einstein to study this in hone? No, we have our be which just wrote a grant we need money for that. Yeah. I guess, you know, I have a whole framework around nutrition, which I'm happy to kind of walk through as we inhale our dinner tonight. If you decided, by the way, if you on Indian Turkish Persian, yes. Greek all of the above with, you know, because it's raining out. So I guess one of the things we could do to the closest with them. Yeah. So my concern with time restricted feeding which I practice quite liberally is I'm worried it is not a significant enough deprivation of nutrients in humans in other words, I think sanctions data is so impressive in mice. You know? But I think that for a mouse to go sixty hours without eating is an enormous task. It might be the equivalent of us not eating for three days. And now that said, I I'm struggling to see a downside of time restricted feeding, and I know that vaulter and others have said time restricted feeding somehow bad. I don't accept those arguments. I'm not convinced by those data. But. This is a very interesting question, you're asking I would argue it's the most interesting question of all because if we understand the time course of that all of a sudden, we can program nutrient exposure and have you looked at that acid in the presence of rapamycin her metformin? I didn't but mid four main unim- arena Cuervo is using formulas control for autophagy. Okay. Activates autophagy really will. Okay. So that's it. I'm talking about in vitro assays. Okay. But we haven't measured the in in Bache. It's that the one thing I should say. I just don't forget anything absolutely in expect to the mid for me just reminded me spectrum of myth formed studies. So a reviewers wear saying, you know, okay old data on the biology that you showed was from rodents, and we don't know the biology's relevant to Uman's. Okay. Although, of course, the preliminary data Newman's are much better than in rodents. Right. The association with diseases. So we had the clinical studies small clinical study, which we took fifteen people that are seventy five years old, and we gave some of them at forming for six weeks and other placebos, and then we cross Stover, and he was blinded. And we took it at the end of each. Period with two biopsy from their muscle and biopsy from their Eddie postition. Okay. So motley, and we looked at the transcript and the metabolic, but mainly the transcripts in the tissues to see affects them at me and their three interesting things. First of all when they brought me their clinical results, you know, in selene Homa glucose in all there was significant effects in many of them, statistically significant effects. I was expecting more. I started to try and break down. And then we found out that the people who were lost on metformin, although it was half of the people had much more significant results than the whole fifteen people. Wait, explain that. Again, the people in the crossover who started who went placebo to metformin had better effects on metabolic parameters. Relative to. To themselves or to their peers relatively to themselves because ever this was a person to person was in person a paired t test, and the reason these that probably the two weeks wash over is not enough when you fix the aging lasts for awhile. Okay. So if you got forming, and then placebo, you didn't really you went halfway BIC. Also, by the way, because mitt formulas associated with weightless than they lost the weight that Don itself really made them on the secondary. What it's funny bring that up. I'm glad you were mentioning that. What do you think explains the weight loss phenotype of metformin? So when I started taking metformin, which was two thousand ten I didn't mess around. I just went straight to two point five grams a day, I didn't even mix it up. I don't think I took it be. I mean, I took to twenty five hundred milligrams. First thing every morning and after a month, I lost quite a bit of weight. But I was also nauseous twenty four seven. I mean, the thought of eating was repulsive to me I still ate exercising and doing on my usual shenanigans, but clearly eight less just because of the low grade feeling of nausea today when I prescribe metformin to patients I have them start at five. Hundred QA chess than five hundred b I d than fifty five hundred in the morning, fifteen hundred before bed than one gram be ideal sort of standard dose, and I see far less of that nausea, and I see far less weight loss. What what other mechanisms do you think it could explain the weight loss? So could it be locked ESI going up? You know, just like he tones you get a substratum additional substrate. Yeah. I don't know. But look I started mid forming several years ago because I was free diabetic my doctor delete sites before I'm glad that he did. But it was before I thought much about eight, and I was just prize after three months to realize that I lost the, you know, seven or eight pounds. I was surprised because I couldn't I wasn't nauseated. I wasn't anything. I must've been less. I I was less hungry. I reacted better. I reacted better to my buddy right to my left in maybe. Reacted better. And I probably didn't eat as much not totally not noticing it. It was a surprise to. It's funny. I tell patients not to expect that because I don't I don't like the patient's thinking of this as like a weight loss drug to me that sort of is not the right way to think about it. But I've never had a great explanation. And by the same token, I have had I should be clear. I've had also some patients who have they've come back and they've lost ten. These are patients who were not overweight. This is not, you know, this is someone that by everybody's standard would be completely normal weight. You know, BMI's twenty four body composition as reasonable and comes back in, you know, in three months, and they've lost ten pounds. But I guess for in my at least in my practice that seems to be the exception not the rule, but very very interesting to know. Of course, you wish that was more than a two by two two week which that was a twelve week by week. We are doing the same thing with audibles now and we're doing longer study with longer washing beard because we wanna. Get away from it. But Beckham at formula said that's one thing is forming last issue the second thing that we showed that most of the transcript changes were relative to this to the tissue. You know? In fact, it was more free fatty acid metabolism. In the muscle was more pirate metabolism. So it was appropriate. I was wasn't the mid forming, you know, the mid forming part but in both tissues they were genes that are not metabolic genes. You know, like beer CA one or Maya five, bro, jeans and other things that are related to aging, but there are not metabolic they changed by mid forming. And other words, the concept mid form as not only metabolic, it's aging. Okay. BRCA one changed. Yeah. You know, some other gene genes associated with genetic with the DNA repair changed significantly. The second juicy in the muscle, by the way, if you still have biopsies I'd be very curious to know, if they lactate transporter out of the muscle, I'm blanking on it. It's MC t to in other words as people make more and more lactate in the muscle. Do they get more and more efficient at shuttling back to the liver? And if so you would expect them t- to transit, gene expression changes by that. You know, we have the road date didn't come up tell you didn't come up as a winner. But that doesn't mean it's not it's not change. And you looked at genome or you looked at looked at messenger as well. Looked at Amore NS script. It's all Marning rocket. So you should have seen it. If it happened will if it was highly. I mean, they're hundreds of changes. Okay. So maybe it was underpowered see that difference significant changes. So I can steal Unser. You I can see us you specifically, and it's all Rene sick. So it's really. Good. It is will be good. You know, if if I take that and see that it can be without taking into account that their four hundred other changes can be significant in the other thing, though, what you do with transcript you look at upper regulators of the system, and there's a way to do this with everybody doesn't out. So if you look at the upper regulators, you get back to the same things that are acting aging amp behind as emperor. Although spots was were affected by metformin accepted. What you measured below is the tissue specific affects, but it was all related Beck straight to aging. You know? So so we we really connected not only the clinical data biological data in humans to tame study at it's wonderful. It a few years ago in my my father was diagnosed with cancer. I immediately put him on metformin, and you know, in his infinite wisdom, his primary care doctor took him off it because you know, why would you put on metformin? And in the end, my father decided his primary care doctor knows much more than I do. And so remains off metformin. But certainly this discussion because I, you know, I probably know more about metformin than the average person. But this discussion has been completely eliminating. There's one of the thing I want to ask you about which is all of the discussion around NA NASD. I mean, you're you know, quite a bit about this. What is your take right now based on the state of the science that we have which admittedly? I think we're just scratching the surface of is far as first and foremost just at the mechanism level. Do what is your belief that orally administered nicotinamide riboside can actually make it into a cell? I don't know if you've seen it. But Josh Rabinowitz his paper over the summer. Would suggest not most of this is going to the liver. So wouldn't this sort of call into question the company's there's two of them right now. Chroma dexin. At least him that sell basically nicotinamide riboside, plus or minus terrace delbene, what do you think explains the reported efficacy of those agents in light of Rabinowitz? His and Detroit's or study first of all they're Rabinovitz study was also criticised. Okay. Time course and other things which okay, I'm just saying that. But I think really the biggest issue here. I want just to use this opportunity to say that a lot of what we're doing is not based on clinical studies. Okay. And it really just underlines the fact that unless you do clinical study, you can remain guessing. Now, I'll tell you. I'm taking a good preparation of. Okay. Tell the listener the difference between NRA 'em because they're both precursors to NASD. E but there's a there's a subtle difference. Yeah. And I I don't know. I I don't know to explain that. Really will I I don't I don't care that much. Okay. But by theory, one is lightly more stable than the other, right? It's stability issue of ability issue. But they'll fight at we. We don't know which is the better, and we don't know which gets to the tissue, right? But what I want to what I wanted to say is the following. So so the answer is also it could all be water. Okay. It could all be the you say that as you. Hold up a bottle of topa Chica, right? Sorry. You didn't see that in the microphone? Okay. But what I'm doing? Now is opening my feed beat okay. In one of the things that defeat TASR is sleep. Okay. Do use feed bit. No use something called aura which works much better. Okay. This really measure sleep. Well, do you get also the deep sleep and the? Yes, REM and all that. Okay. Since I started taking amend, and it might be acquainted. So I have to stop and start again. But my sleep is being much better. That means I have in the beginning of the night. I have much more deep sleep in the end of the night. I have much more area. And I thought if there's anything I can say about it is that just because of this association. Okay. But I don't believe it. Right. Because it's not a it's a it's my it's manage imperial and many cynically of look, I was fixation. I don't know. Many things could have happened details. The men by itself or do also pair it with Tara still being are just there ser- to inactive inter just in. But it's a good. It's a good suggestion. Maybe okay. But then I run into immi-, you know, who's chigney my he's from Senlis, and he has his own patents and studies in Japan on an amend any tells me unprovoked, he says, you know, I have two hundred subjects and one of the interesting thing is their sleep patterns improve. They get more deep sleeping the beginning of the night and more REM at the end of the night. In other words, he tells me what I've noticed. And it's makes me just think, and maybe believe in maybe hope that something is getting into the sales. And that there's a relief fact at least on sleepy didn't tell me any other things. But really, my Unser is we don't really know enough. It's it's very hard to measure effect because the Senate DIGOS and and goes away. And and you know, what system can you do? It's very hard to measure that and without clinical studies that are really went well controlled I think it's going to be hard to to just support that than that's me as a conservative scientists in warm says that even at formative everybody says you have enough data. No, we have to do the clinical study to prove that. And that's where I really stand. And it seems to me that. Intravenous administration of NASD. Also, not particularly helpful though. It seems quite popular in the sense that I I'm not I haven't seen compelling evidence that giving an intravenously makes its way into the cell either. So I think the development interesting development will be to develop a drug and the drug will be precursor that will get into the blood outside of the liver outside of the liver guy. Exactly. So if you could give an are subtly or intravenously that strikes me as very interesting saying that there's a lot of data in rodents. Where also you look you give it in different ways, you give it summing water, but some are vase, and maybe that's different because one of the problems that maybe if you go deep enough, you can bypass the by circulation ride, you can bike something. So, you know, but the Viva studies are. Good studies. Okay. You just don't know what it means to you men's well narrow time check here we've been we've been going at this for a little while there's a lot more I want to sort of pick your brain on. But we also just sit down into this again sometime I wanna make sure you've said at least as much as you wanna say about metformin because I think that to me is, you know, you're you're at this point, arguably one of the world's experts on a drug that just to put this in perspective. I think Lou Canley who's obviously a close mutual friend of ours. And James Watson who I don't know. Personally, have both said quite publicly that metformin may have already saved more patients lives from cancer than all other cancer drugs combined or something to that effect. This is a drug that I think with each passing day more and more people are beginning to learn about beginning to ask questions about. And my hope is that if nothing else this podcast is a place that people can listen to this episode if they. Can't go and read sixteen of your papers. And they don't necessarily want to get you know, that far down the rabbit hole. But to hear it from you and not for me or some other schmuck who doesn't know much. I wanna make sure that if there's anything else, you wanna say about metformin that that you say so and so is there anything else that you want to add let me do one truck tickle thing in one a little bit more philosophical. Okay. The tickle Zing. Really surprised me? I was I was giving a talk somewhere for lay people. So it was organized by university, and they invited people and to their surprise three hundred people in the audience, and by the way, mytalk wasn't about mitt forming. Mytalk mytalk to the titles of my talk is usually how to how to die young in a very old age. That's what I might title is. Usually if I can get away with it. That's the title. So people people are coming as they're entering some of them come to me and say so how much of it for. Should I take? Okay. So I started talking all of a sudden I said let me ask you something who hearing the audience is non diabetic and is on mid forming. And please you you know, you don't have to just if you choose to hope so how many half the people where was this talk with university. I don't wanna what city can you say what city was it in the United States? No, okay. So, you know, the in other words, the prophecies out which makes me a little bit worried about the study when we first world Street Journal is the first picked on tame wrote an article the next week we had three thousand phone calls and emails of people volunteering to the study. Which is what we need to do the study. And I thought was just cut your trim that budget from seventy million down to sixty five. You cut all the recruiting or how exactly except that. Then you really by Osam, then you realize just a minute. Those people first of all we didn't advertise they hit to find my phone number and Email and second Dail do they're doing other things, you know, he's like with estrogen by us. They'd probably exercising and stuff like that. And then when I started getting emails like, I'm volunteer to stir to the studies long as I'm not on the placebo. I thought you know, if people care so much if they'll figure out there notamment form, they'll just get mid for me. So from a recruiting the three thousand we we outlawed those those are not in my study right up. So I wanna say that steel we haven't done the study. Okay. We haven't done the study. So you'll be between sixty five and eighty. Okay. Just no we haven't done this study. We don't know if it's safe as it is in young people. And so we don't have really clinical study with evidence that this is good. And I'm I'm just worried now that part of the reason to do this study is because if it's not good people should know, also right and not take another drug. Okay. Not that they've been leaving it. But it is possible. The second thing that is more philosophical. So I said before I was invited to vodka actually was invited twice the second time. And I'm very close to cardinal revolves e who's number four in the pontiff's. He's his in charge of science and on arts including science, and it's interesting because the Vatican basically says we don't wanna be Galil galley situation. Again, we don't want to be in a situation whereas science sciences, so right? And we're so wrong that we don't know what to do with it. Okay. And so they call me, and they said, you know, we have a meeting in the. Vatican with like you to talk about aging. Could you come Senate said sure shirl common, then I'm going on saying remind the keynote speaker they said the keynote speakers are the pope and Joe Biden who was I. I. Okay. So still coming. So that's how it goes. Joe Biden goes up and explains his concert initiative, and how did it is because when you have concert you having the concern, maybe five other genomes, and they're also different than every other concert like that in the world. It's really a mess. Then comes the pope and says, you know, I still hope that there be one little peel cheap for everyone in the world that will cure, whatever Concer they were appropriate now hopes to, but then I go up, and I say wilder is actually a cheap peeling that. And I don't know if it cures any concert in the world, but he can it can prevent a lot of the concerts in the world. And actually, it has a side effect that also can prevent a lot of other diseases in the so it was like. So it was like the, you know, going back to aging and the risk of aging for H related diseases and how impact full and cheap. It could be a compared to treating cancer or something like that. So I think the prevention of aging is is really a good place to be. And I think because we went from hope to promise, and we have to realize the promise Zing life is going to be very different in the next decade with our advance last question not to end on Downer. But let's try to figure out where a blind spot could be what where could we be wrong? Obviously you, and I share more in common in terms of philosophy and points of view than I even realized before we spoke, but where can we be wrong? So, you know, tell you what's my optimism. You know, we have the European have nine pillars of aging. And we have seven pillars of aging, and they're all inter connected. And when I say interconnected, a just spend the time with Annamaria Cuervo this morning when she fix tougher g. She fixes also metabolism. Okay, there when when you start doing things in anyone's of those feelers you starting proving the others now where we could could be wrong is we don't know what is the impact of each of those possibly in Uman's. Okay. Most of our data is kind of animal data. But I think our phobic is that we all age defended of in aging is that aging is universal every every animal has the skin the hair the skeletal the frailty. It's very universe and those treatments are emit forming a mice and you give it to any animal almost delays the aging there. So. I don't think we're going to be wrong. I think that may be some poss- ways will not be so effective. Some of them will be harder to treat maybe. But I think we have to effect three four and we're right on our way to do better. And that's just the beginning. And in the tame study Illit will be one to one male to female. Yes. So we'll also void that other. And have you powered it such that men and women are different animals will know because all our data with formula. And we looked carefully to the other. They didn't see any gender effects on any of the outcomes. So we are swimming that so you're powered as though the gender darn different signals like we would do maybe Rupp amazing. You know, we'll near this has been fantastic. You know, I was sick the last two days my voices gone. I feel like crap. I was like, maybe we should postpone it. But then when I woke up this morning. I was like there is no way we are postponing this discussion because I cannot wait. Eight to have this discussion. So thank you so much for for coming over. It was great. It was it was great because you ask really great questions. And also, I'm now quite hungry, and I'll be happy to have dinner with you. Now, we we are going to put together a seminar on how not to caloric restrict. I'm right only tonight. All right. Thank you near. You can find all of this information more Peter Tia, MD dot com forward slash podcast there. You'll find the show readings and links related to this episode. You can also find my blog and the nerd safari. Peter Attiyah, MD dot com. What's nerds afar? You ask just click on the link at the top of the site to learn more. Maybe the simplest thing to do is to sign up for my subjectively, non lame once a week Email where update you on what I've been up to the most interesting papers, I've read and all things related to longevity. Science performance leaf it cetera on social you can find the on Twitter Instagram Facebook, all with the ID Peter at Tia MD. But usually Twitter is the best way to reach me to share your questions and comments now for the obligatory. 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metformin diabetes United States Israel glucose intolerance mechanism of action lactic acidosis nicotinamide hyperinsulinemia California yale Barzilai Cornell growth hormone Peter Attiyah Newman Ataf Aji Peter
Hope & Healing with Cannabis, Foods for Brain Health #1074

One Life Radio Podcast

43:55 min | 1 year ago

Hope & Healing with Cannabis, Foods for Brain Health #1074

"The content of the following program is not intended to be a substitute for professional medical advice diagnosis treatment or cure always consult your physician or a health professional with any questions. You may have regarding a medical condition the baby do you wanna go higher baby. You're in the right place. So you're listening to one life radio. This is bernadette with diamond gray adriana toast nubby mandoza and jill leinna and how's everybody doing good to be here happy day happy day the day after labor day. I'm a little weird from being off. You're wearing why isn't attack against the rules whatever they are. Oh that's always v that's old school. I know this is actually from the fall. Pre fall my mistake. Whatever isabel mirant and you know my friend is in that industry and so she gets me. All these great finds the shoes that i brought you man. They're so hugh of italian billion hoti black boots that were actually hundreds and hundreds of dollars show you and i got i got i got him for a dime not ryan dying but like so cheap you feel like you're stealing those are so throwback from the eighties and i love the height of the he'll like just the right to not i love you can walk like a like a regular phone things you can wear these with sway. Oh a lubbock. Ah i thought so cute us. I got an eighty percent off credible and she's got teeny tiny lead to that and i'm going to be leather soon though the got another one too when she's a size five she's got a tiny foot so the end of the season a lot of times the the forties or forty-one which is the ten eleven or the fives get left on the rag looking of the right so uh my favorite colors are blue so this is awesome love those could go with tons of stuff on there so love love love cool. Who'll lifestyle too excited such an incredible deal too so i love getting a good deal all right yeah so <hes> so i laugh have to here friday and my way home i got rear ended which is not that big of a deal. It happens to a lot of people every day thankfully. I don't think i haven't been to a doctor or anything but i'm pretty sure. I wasn't like you know injured too badly but i did get a headache like shortly after like within fifteen minutes i had a headache and an earache which i thought was unusual unusual and so i went home and then a friend of mine dropped off a dog that they'd found in a park. That was an abandoned so oh doug. I named him charlie already. I can't keep them. I've got too many dogs if he was a female. It was a female dog definitely would it would be like a shoo-in. Can you know because but i've got so many male big dogs and they just the ratio's like way off balance. I have i have seven. I have seven male dogs and to female does but like tom willie are so sweet. Have you introduced them yeah. I feel like they would be the perfect tree. I don't think so no no 'cause tom. No i know what my my thinking yeah no i did because i tried to mix it up all weekend long <hes> and no they. Tom tried to kill him through the fence. That's not gonna work. So what am i gonna do with here. Are you vagabond yeah so i have the emergency kennel at the front of my property and that's where he's been and i took them to. I took him to shake shack. Saturday night. Got him a burger and took him for a ride yeah. I knew what a dog is just like a black and white like a mutt like a medium sized. He's like forty pounds. Okay he'd been neutered and he's four years years old. I found that out and that so his he had a he has a chip but chip says that the dog is deceased and the number was shut off. How does that happen. Does oh so maybe they must have got lost and then like just should i have no idea must've thought he was a goner and then yeah then interesting wouldn't give us a lot more information. They wouldn't give his any name. We're going to try and get the shot records <hes> than to send it to the vet so wait. A minute chip say who he who he previously had belonged to they want is they won't give the information out there very <hes> larry very secretive but can they contact. We found your dog. It's you do you think it was lost. It's not dead. I mean they need to give it to you but can't the vet or whomever gave you the information about the chip contact people. He seems like he was treated. Well because he is such a good boy you know but he kept hanging we think he was in a guys truck or car or something. Somebody took him in the car all the time because he would not get away from my subaru. He got hanging out the door and jumping up like hey where we going so i thought you know he seems pretty well behaved and so i took him to shake shack settlement so no wonder why tom what's your talk tom. Toms pissed. Tom and willie shakes out and make trump. Gotta go. He just showed up and make isn't having an knicks pissed. I can tell you the jews all messed up. He's like what's going on here. <hes> rougher make lately. I now all these dogs. He feels intimidated rough rough. I know lorne life but yeah so so. My friend said take a few of these so i did. I had taken after i stopped hallucinating. I slept really well joking of course. What did you do this weekend. Anything fun. You guys. You know what i felt like. I was like party central for my kids. My kids had a lot of playtime play time with friends this weekend. So every day one was at one friend's house and another friend was over. It was lots of stuff with the kids which made them very happy and we had a neighborhood get together together one night which was great <hes> this visiting and you know playing some. Excuse me some games and things like that but lots of suffered the kids this weekend which was cool. You know they yeah. They have their low. Social lives too so we were we. Were you know socializing them socializing them. That's always good. Well my my my weekends kind of a blur. It was long it was like just young enough was up with yesterday was is it just me yesterday felt like it was two days in one day. I i really yeah. I got up at seven. I think the first time and then let all the dogs outside. I'm wired them then. I went and laid back down <hes> and so but i felt like yesterday like when is going to go down. It's like the universe was trying to play some sort of joke. I felt like it was two days in one. Does anybody else feel that way. Calls it to one four seventy. They felt longer than a normal three day weekend because usually with my kids they need like they would love to have a couple of days but i felt like it was just packed salahaddin yeah. It felt longer than three days <hes> but you know what yesterday i don't know. I like the whole weekend was a blur. I don't know what happened. My kids very busy very social. You you know yeah. We had a little bit of time to. I cleaned out my car this morning. I have to take anything interesting because i have to take it in and get a loaner car a couple. I'm sure that's going to take days to fix it but you should have seen all the stuff old out. What's the craziest thing that you found because i can't even imagine who say it on the air one life radio banner thing. I agree three scarves all the equipment. What else did i how many outfits one hundred books. I didn't have any outlet. I had two pair boots that i was gonna. Take dino's like i'm going to say it awesome that no no no there was about one hundred bucks. I shouldn't take a picture and they're all in my kitchen table right now. I gotta alphabetize and put them back when i get home in my spare time tonight after i take care of is animals but <hes> yeah charlie peed all over that that's the name of the new dog charlie you need him. He's yours all over the construction. Would you know they're fixing xing. My two porta shays that leak and thousands of dollars worth of damage but you know what happens and you just have to you know roofs. Are roofs are tricky. They can be super <unk> tricky early. I mean he's really i mean i just i can just see this guy is like i want to make this place. Would you like to dogs. No in dog is to buck two dogs one dog. I have is like having three more kids like i can't. He's so smart. He's just rascal yeah. He's no now. What's his name baxter baxter. Is he a little more now. He's a french poisoner. He's three very smart but he doesn't listen to anything i say and he looked everything to my husband really but then at night he has to be sitting by me touching me like it's all things me if i don't give them like one hundred one on the dot pets per day than stay off. It's like he's very but then if i try to instruct him in any way forget about it yeah i mean just forget about it yeah. He's such a turn. Well yeah dogs. I i love my animals so much. Charlie hit the big time. Now i mean he was even at royal blue grocery yesterday afternoon i took him. I got him some stake in super green little. I'm gonna someone dropped me off at your porch real. Oh my gosh but you know we have a fantastic show coming up today always with joel lane. She's going to be talking about seven foods for a healthy brain rain and food preservation tips. I love this. I forgot we were gonna talk about that and then what effect is calorie restriction have on the brain. I'd like to know because i'm calorie restricted right now. Oh that's what i do. I don't eat until after the show and sometimes i think jack's with me a little bit. I want to hear what you have to say and we have a special guest coming up to donald sage. She is a mother their wife and health educator who lives in denver colorado. We're gonna be talking about hope and healing with cannabis so stay tuned everyone. You're listening to one life radio. It was my friend ebay all thrown on the road one life radio is brought to you by our sponsors great companies companies like sun warrior plant based protein used the code for twenty percent off crazy water the only mineral water bottled in texas environmental makers of tariff flora a novel broad spectrum symbiotic formulated with a combination of spore form probiotics and advanced food based ancient probiotics abiotic paleo magazine the wellbeing journal the international society of sports nutrition be sure to go to our thorn research dispensary on our website right for twenty percent off and free shipping. Thank you for listening to one life radio right little jackson browne. Welcome back back to one life radio. Everyone this is bernadette with diamond gray vienna badian toes nebi mendoza jill lane and our special guest today donald sage. She is a mother wife and health educator who lives in denver colorado. <hes> this is a very important segment. Were about to embark on <hes> because there's a lot the people out there listening that will benefit from this <hes> you know i think of a wonderful woman that we had on the show a few years ago actually last year mitzi wigner and her son gavin who were cured from terrell. It's her son gavin was cured from herat's by <hes> reaching out to the realm of caring and getting on oil and cannabis and that's what we're talking talking about today hoping hailing with cannabis okay so donald. Let's let's let's really dive into this. Can you tell our listeners more about c._b. And what the realm of caring is i sure can so. I'd like to say that i i learned about phoebe and cannabis out of necessity. My daughter suffered to really serious concussion so i kind of dove within headfirst into a sallow pond but fortunately i was in denver and <hes> c._d. Is very unique and special because it can reduce inflammation in nervous system. That's really the bottom line. It takes the pressure off of your nerves. Though you think anything dementia parkinson's tremors concussion region threat anything in your now muscular system seems to be dramatically improved by reducing inflammation with c._d.'s <hes> well i i it people have so many remarkable stories and so so what happened with your daughter. She had to concussions where they close together. He they played competitive volleyball and she had a concussion in the spring of two thousand fifteen recovered over that year and then suffered another one volleyball. Wow and that's that's really common. Joe lane played soccer in college and we've talked about this many times that a lot of injuries happen and soccer her dante soccer believe it or not the number one reason why females particularly get concussion is actually head to head contact. It's not from the ball hitting the head. Which is what my my mom was always worried about. She didn't want him to do headers. That's actually <hes> collisions head to head or you know maybe elba ahead or something like that so it's far more common than people believe in often times it goes unnoticed undiagnosed just because maybe someone doesn't fall down and pass out or something extreme like that ankle to think oh. There's something wrong. They might be dizzy. The athlete might not say anything that my unqualified person around to check pupil size and you know all that sort of thing so it can be hard for a parent or coached even know that had happened honestly yeah yeah so so continue on if you would please donna her first cousin concussion in two thousand fifteen they had the standard medical practice was called reap where you basically rest restore your body out of pain you quiet the brain. You're in the dark room. No screen meantime and you call the nervous system and the majority of concussions resolved in seven to ten days however my daughter had what they call post concussion ashi syndrome where you have residual pain they say residual pain that we had constantine that never went away <hes> lasted several months <hes> and we discontinued to monitor her activity <hes> reduce stimulus stimulus shen and <hes> you know you'd chiropractic cellular therapy cranial released technique <hes> we had her eyes checked. We did all kinds of what we thought. Were for supplemental support for health it took nine months for her really to get back to having a little bit of a sparkle in her eye that first one wow wow and so and then she that she had a second one. At what point did you start using cannabis and why well in twenty sixteen ecksteen when she had her second concussion. There was a new study out that said hey you know suck it up buttercup. Just get up there and go to your pets and i'm looking at my daughter and like you just tell like she wasn't really there. <hes> we went through <hes> the severe medical pathways with <hes> neurologist adjust. We did <hes> heavy heavy prescription drugs. She was offered both concussions multiple times to take anti depressants which the decline in the sixteen concussion did an i._v. Cocktail of depakote tore it all and benadryl and attempt to reboot her brain hands down made her pain worse made her more irritable and very toxic and unhappy and watson win after that second concussion we said look. We're at the end of our rope. We've tried rusty and waiting in work. We've tried everything that you you wanna do except go down at which wouldn't work anyway. I cannot you know what i have to tell you like that. Puts a fire under my rear end when i hear that <hes> an irresponsible medical doctor would offer <hes> depression or prescription drugs to such a young child when it wouldn't even help the situation you the <hes> concussion has nothing to do with depression and anxiety we yes parents we agree now. Here's the dilemma and that's the gray area because these doctors they don't have a lot that they can offer that can work and help and ashley was really struggling with you know her her grades and her identity and being an athlete in a scholar in all of the social things that we're really suffering in her life. Were there things for her to be depressed about. Heck yeah plus. She had a pain. A constant headed here. Imagine constant headache from month to month like that really can create symptoms of depression. It wasn't depression person <hes> and so is that when you so i'm reading here that that's that's kind of when you you eventually began supplementing the c._b._d. With the t._h._c. you see to obtain more comprehensive relief for your daughter's concussion symptoms correct. That is absolutely correct. I shared all those things that we went through to show you how how amazing recovery was with c._b._d.'s after twenty or thirty minutes with twenty milligrams of charlotte's web cannabis oil which is the only for the first time in his mom doesn't hurt but it's gone. It's really gone yeah. It's it's is truly amazing. In fact <hes> charlotte's web was a longtime sponsor of one life radio then they got a new marketing director. You know they make they changed things sometimes but <hes> but anyway <hes> charlotte's web the realm of carrying the realm of caring. I have sent so many people there i have because i've heard i've never been there. I've never called there but but i understand that they are an amazing organization that helps so many people there really are and i jumped in. You're not knowing i wasn't pro cannabis or cannabis. I would pro- healing my daughter and we actually got a clue when we were reading something in the denver paper about the n._f._l. L. wanting to get t._v._d. Approved anymore <hes> the n._f._l. Injuries and it just kind of snowballed from there in the realm of carrying was a a fabulous resource. They helped me understand <hes> what products to get. How do you figure out a therapeutic dose. I actually found them after i started started experimenting with it because i was just so excited at the possibility convinced that if i got their brand i knew it was clean. It wouldn't hurt <music> her and for goodness sake is really healthier yeah well we've had we've had you know we've got story. After story i could recite of guests that we've had on the show with children that were suffering that i think of <hes> <hes> my gosh a couple of years ago <hes> the <hes> lexa mortell <hes> they had to move that actually had to move from texas axes to <hes> to colorado save their daughter's life and i mean just countless stories like the one i said mitzi wigner and her son <hes> gal gavin who <unk> who had tourette's syndrome so so bad that he couldn't even go to school and after two doses of c._b. Oil <hes> the appropriate dose which i believe the realm of carrying was the one that told that guided them through the process as well <hes> and he was he was he was he was cured in no you're not supposed to say that but the tarantula the <hes> you know all the shaking and trembling was gone and he was able to go back to school within a couple of days when you hear stories like that. I don't know how anyone in washington or an and any government agency could think anything other than medical marijuana and c._b._d. Oil should be absolutely legal in all fifty states. Would you agree wealth that i do okay so what are the current laws regarding medical marijuana and c._b._d. Well i can speak in the state of colorado when we were going through this with ashley so she was born in two thousand which is when the big movement to can legalize medical cannabis for happening denver and i had i was living in the mountains. I was busy. Have you my home birth baby and you know not in the city with these marijuana pothead people honestly i just i didn't relate or understand i wasn't educated to the benefits a seven yeah but faithfully we had industry leaders and pioneers that made it possible so that when i circled back and my baby needed that it was available all the became available in two thousand and denver everybody pretty much knows colorado's the pot capital marijuana headquarters yeah now. It's also <hes> legal for recreational use as well <hes> <hes>. I'm a social worker. I know how to take kids away from their parents and so so i started this process with ashley i really i followed all the rules. We got cars. I actually even though following all the rules rule in wasn't using t._h._c. I still felt a little bit like i would be naughty on yeah. Go ahead. I'm sorry say fortunately now even over the course of just a few years that stigma is lifting because like you said all these stories that you sure shown that you do on your show that help educate people to demystify and help us understand the beautiful plant that he sure yeah really wonderful well our constitute. Our constitution was written on hemp paper. I'm one hundred percent sure that along with a lot of other stats sykora out there but you know cannabis is a beautiful plant. It should be legal <hes> if federally and so should c._b._d. Oil federally that he'll so many people and by the way we have an unconditional it system in our body that needs fed by cannabinoid which you can get in some other plants but i just don't understand why so so many people still to this day leave themselves uneducated about this subject and believe that you know that marijuana's from the devil <hes> or some crazy stuff like that. It's it just seems so <hes> ignorant to me. It really does what part of why i'm so thankful to be invited on your show. I wrote my article <hes> <hes> and it was published in the well-being journal journal everett and for them for over twenty years so kudos to scott minors. Yes <hes> people just don't know what what they don't know. You only pay attention to what you're being right through media for example yeah and you won't get the whole story and you'll get whatever you know. Unfortunately pharmaceutical companies have way too much power. We see it <hes> with the opioid loyd crisis. We see it all over the place. We see it with vaccines. I mean i could go on and on and it's just an the case in point your daughter they were going to prescribe of her depression drugs which by the way after two months would be very difficult for her to get off of and would do all kinds of damage to her brain antibody. I'm sure you're familiar with dr kelly brogan. Who's been on the show. Multiple times is a new york times bestselling author. I highly recommend her book as well for <hes> getting to the root of a a lot of issues that we're discussing on the air today such a pleasure donna thank you so much. I hope you'll come back. I love you. Thank you for all your work. You're doing <music>. You're welcome thank you so much. Donald sage and i encourage everyone out there that perhaps a child that perhaps is suffering from some of the same things that her daughter ashley check out the realm of caring. It's the r._m._c. dot u._s. Will be right back. You're listening to one life radio. One life radio is brought to you by our sponsors. Great companies like sun warrior plant based protein used the code. Oh l. are for twenty percent off crazy water. The only mineral water bottled in texas in vibrant medica makers of tariff laura a novel broad spectrum trim symbiotic formulated with a combination of spore form probiotics and advance food based ancient probiotics paleo magazine the wellbeing journal the international society of sports nutrition be sure to go to thorn research dispensary on our website for twenty percent off and free shipping. Thank you for listening learning to one life radio. You wanna come back to one life radio. This is bernadette with diamond gray. A adriana santos v mendoza and jill lane joe lane is a pro athlete health and nutrition coach and founder fuelling champions a three step sports performance indepth leading nutrition program bill to maximize the potential of student athletes and the parents that support them you can find her on instagram at team fuelling champions or her website repealing champions dot org today. We're talking about a lot of stuff. We're mixing it up. We're gonna really have a big big. Show great segue from what we were just talking about though because we were talking about things that helped the brain absolutely people think the brain is just you know the object. That's <hes> contained in our school but not connected it to the rest of our body. Medicine unfortunately still treats it that way but we forget that out of the base of our brain is this long tail of you will our spinal cord goes all the way down are back and then at our but all these little tentacles go out down our legs our brain literally as everywhere yeah take care of our whole body to take care of our brain well. That's why him works. Works have absolutely it does and <hes> and we haven't ended cannabinoid system just like we have a digestive system a nervous central nervous system a lot of different systems gums and it needs fed properly and it's always great to have you in studio joe lane. She's been on the show since the very beginning. Almost i think week to <hes> signed her up. We've been talking ever since but <hes> she's incredible. She as i said she's a pro athlete health and nutrition coach founder fuelling champions today. We're finishing up what we talked about about a couple of weeks ago. <hes> the what effect does calorie restriction have on the brain. So what does it what what would what did we not get to. We'll just as quick recap for those that are tuning in today for the first time what is calorie restriction. Even mean is the first thing to define so clerk restriction in the scientific literature usually means that you reduce the amount of food you're eating per day by around half and so if you eat around half of what you're eating or you know for some people's between five and eight hundred calories or less per day you are kind of in the realm of clark restriction now when you do that a variety of over a period of time so usually it's a day or two or longer a bunch of things start to get triggered in the body that for most people are really beneficial so when it comes to the brain something really cool that gets triggered. Are these fancy molecules. They're often in called longevity. <hes> proteins called sir to ins. We asked her to remember yeah. Okay so so tunes really are the kind of things in our body body that keep us useful and the cool thing about it is that fasting potentially happened. <hes> triggered to start to windsor certain actually nutrients sediment research to mimic caloric restriction because because let's face it none of us can eat less than half of what we eat every day for an extended period of time and there are some religious groups that do that the monks i mean there's there's people groups groups very small that do it but there's a lot of research happening just like honestly like canvas right now into the medical benefits of monitored caloric restriction or certain variations of fasting so the brain really benefits if done appropriately yeah it's fascinating all the science is so fascinating you said said something about a supplement and i know that i'm curious. I know people listening are curious. What supplements a supplement helps with longevity well the one that's there's two that have been shown to mimic the the effects of caloric restriction one israel take that yeah. I drink lots of red wine right. I know that was coming but here's the thing and the cool thing his though i mean they've shown in in in an article that we're kind of jumping off this conversation from they've shown that people who take virtual around two hundred milligrams a day have some of those are due to an and cognitive benefits that caloric restriction provides but the thing that catches people up over time and this really goes back to even the discussion we were just having around concussion cussin' as there's another molecule in the body called n. a. d. and when we have a lot of repair that has to happen in the body especially in the brain. Our body can run short on n._a._s._d. Exercise can help produce more n._a._s._d. But my favorite thing that helps produce it is something called nicotinamide riboside or rivera show. Ah there's a product called reservoir cell which i think you and i both a wet swells barrasso sell. It's a combat swell. That's tricky trekkie. It's a combination of reservoir trial and nicotinamide riboside in so you can do a better job with what you eat. Maybe come back a little bit on your calories. Exercise good good sleep manage stress and take reservoir sal and get your ser- to and a little bit of love so that age more gracefully so it was very sal is the one that thorne makes yes okay so i take that and then i take a guy a one to <hes> and but that route what's it called roy what the rodeo known pinot midas something the one you just talk to my right beside there. You go that that stuff okay. That's okay is that it will have. I guess thorns doing it is legit there was a there was a group of to harvard doctors that you know <hes> unveiled this new supplement and they were asking huge money for it and i just thought some of the claims that they made were a little exaggerated. You know you. I mean nicotinamide. Riboside has been shown in humans after ingestion to raise any d levels proven and human clinical patties. There's actually back to concussion as we were talking about. A couple of concussion stabbed studies happening actually between thornton the mayo clinic right now on football players in concussion using nicotinamide nicotinamide riboside so it's been heavily researched. There's other research. I think johns hopkins with nicotine riboside an sulfurophane broccoli sprout extract on some other the facts and so yes. You need to get the right dose. You need you know you may need to get it from a specific source. There's other things we're learning about it but <hes> when it comes to taking care of your brain you basically just want to you. Don't want to <hes> age quick. When it comes to the brain you want your brain to be not inflamed. Which is what happens in concussion. It's super inflame flame. I want it to get rusty. Which is what happens. When you eat a lot of sugar and a lot of toxic fats yeah and you wanted to have good circulation and so what about what about ah co q. ten and also <hes> omega omega three yeah so cookie tends really interesting. It's like the spark plug in your car. It's kind of analogous to that in our cells. How's it helps ourselves. Create energy <hes> when it comes to the brain the only thing that's been heavily researched with in high really high doses parkinson's. It's better for the horror yeah and it's mandatory for people who take statin drugs plus medications. If you're listening you're on a stanton your husband or wife on stanton and you're not taking co q. Ten you must take coq ten but that's it reduces co q. ten which over time actually damages the heart muscle which is crazy because that's what you're you're taking it to be healthier and that's yeah dr johnnie boden. One of your favorite on the planet speaks a lot about that really important for heart health more for heart health but again. Everything's connected acted so take care of your heart. You take care of your brain. <hes> well fish oil. You mentioned fishwives fish oil fish oil and actually c._b._d. Go hand in hand and in fact doc c._d.'s kind of like the fish oil for the but the body you actually have to have enough omega in the body to make <hes> your own dodge and okinawa they they work very closely together and sew supplementing with omegas helps again just with healthy inflammatory levels again. No one wants an inflamed brain now. No one wants any you know. Inflammation is meant for acute repair in the body yeah yeah yeah they don't think about the brain like you said at the beginning of the segment they don't think about the brain being inflamed seemed like the body but they're connected and there's no two ways about it. I think if you have a loved one or you yourself are suffering suffering from anything that has to do with brain health weather. Whether it's mood all the way to something like concussion or structural you have to think of the brain as an organ not says it's like a stereo thing like the actual school structure of the brain is it inflamed hasn't been damaged. You know as the circulation to the brain good. I think you have to rule out. All of those things is it. Being well-fed should consider sitter ketogenic diet. You know maybe it needs more key tones. Maybe need to bring your blood sugar down that should be like the first line of defense for brain health and then you can get into the rest of the suffer at least at minimum doom together well. We're gonna talk all about it. We've got a lot more coming up with jill lane. We're also going to be talking about seven foods for a healthy brain and a couple of food preservation tips. I love of these and it's so important because it will save you money so stay tuned everyone. You're listening to one life radio. One one life radio is brought to you by our sponsors. Great companies like sun warrior plant based protein use the code are for twenty percent off crazy water. The only mineral water bottled in texas environ medica makers of tariff flora a novel broad spectrum symbiotic formulated with a combination of spore bore form probiotics and advanced food based ancient prebiotics paleo magazine the wellbeing journal the international society of sports nutrition. They sure to go to thorn research dispensary on our website for twenty percent off and free shipping. Thank you for listening to one life. Radio loves listening it to this song lately. I love and morris. He was pretty hot back in the day. You know four times too do but you know what he's like short short short from england. I can't get over his chest hair photo. Oh no. I didn't see that one could you miss berra gene's looking looking fly. Whatever but <hes> welcome back to one life radio everyone i wanna let you know that you can go to our website one life radio dot com to download and listen to our podcast or subscribe to our newsletter and i think we're gonna put <hes> actually the story of <hes> of a yes yes. We're gonna put it'll be. It'll be a cool story about thank you jill lane russia. Oh my gosh you know you can listen to this podcast to on apple podcast google podcast android stitcher and spotify or you can go to our iheartmedia not i are we only you can go to iheartmedia dot com to listen live or download the free iheartradio app and listen to us from anywhere in the world and a big shout out to our sponsors great companies that help help bring all of this great programming. You companies like sun warrior environ medica crazy water paleo magazine the wellbeing journal and thorn research <hes> as as well as the international society of sports nutrition. We have a dispensary on our website at one life radio dot com forward slash thorn t. h. O. r. n. e. check it out to get twenty percent it off all their products and free shipping is well. I wanted to make a special mention about enviro matica. They're one of our new sponsors and they have this magnetic klay bath. <hes> and it's really amazing so so i'm gonna. I'm gonna just read this from from my little thing that i have here. It's free of additives and synergistically combined with agency salt assault. There klay bath provides a uniquely potent professional grade klay bath formula that you can use in comfort and convenience of your own home but the most important thing is that <hes> it can pull out years of toxins out of the bout body that have accumulated with just one magnetic klay bath so i've ordered domino report back back on it can't wait to try it and of course tara flora. There probiotic is one of the best on the market. If you suffer with not being regular i guarantee see i can give you my personal guarantee that every other day of you take one it is an amazing product and it really does boost your immune system so check it out and environmental dot com and of course son warrior warrior <hes> they've been with us for a very long time as a premier all natural raw superfood company dedicated to providing the best vegan plant based protein powders and supplements go to sun warrior dot com and check out all the products. They have some amazing ones in fact they have a new c._d. Oil coming out. I cannot wait and they have a kito vegan meal replacement drink. That's coming out so and it's plant based so it's it's just amazing and so i want to correct something about that. I said earlier about the constitution being written on hemp paper paper. Will i was wrong or so. They say i'm not sure maybe they're lying but here you go but i want you to know this but so i read the history. This is not history dot com. This is really fascinating is as you can imagine it was an important product and the new world as the american colonies. We're being established. It was so important in fact that in sixteen nineteen virginia passed a law requiring hemp to be grown on every farm in every colony amazing right and at the time it says that the crop was also considered a proper form of currency in virginia as well as pennsylvania and maryland what would would it be like if marijuana leaves became currency in today's world. I have a feeling in some places it is. I think it might be maybe in colorado but anyway. I just wanted to correct myself myself <hes> because that's important right to own it. If you say something that you i i guess it's urban legend or so they say but how do we know that washington isn't lying and you coming coming up. It's a cover up. We need to help cover the sample concerts. We got into it. It's so good to have. Jill always makes me silly she he does <hes>. She's been on the show for a very long time. I'm clearly very relaxed there on the air <hes> she is pro athlete health nutrition coach and founder fuelling champions ends which is a three-set sports performance in athletic nutrition program built to maximize the potential of student athletes and the parents that support them. You can find her on instagram at team. Fuelling champions or website fuelling champions dot org always a pleasure today. Joe lane is talking about seven foods for a healthy brain and we're going to give a couple of food preservation tips. If we have time so you go girl quick list <hes> because i think these are all really easily to access tasty and we're gonna talk about how to make sure they don't spoil because i think we talk a lot about you know how country this kind of what happens all of us. Let's just face crop to crop. We have time for this but i feel like the varies have been so crappy this year as far as how long they last like they go so quick by something and it's like moldy the next day so raspberries doing that right now yeah so first thing on the list is berry's aries because they have all that fiber and those those inoccent like molecules called polyphenyls unlike we were talking about in in the segment before we don't want an inflamed brain so the polyphenols can help with that so berries from a preservation standpoint one. You know you have to eat them right away. That's just the juice raspberry bernie but then i you know i got hit the back end and all weekend. So what do i do. How can how can i because i hate wasting the berries and the money so if you're worried and you don't think your kids'll minal take berries in a day or two but you don't think you're gonna eat them in a day or two. I suggest actually taking him out of the box in langham flat out on a piece of <hes> paper towel l. so that absorbs the moisture because what happens is they get because they're touching each other so closely in there especially if you wash your fruits and vegetables beforehand you need to spread them out air dry them and and then lay them. We don't have room in my frigerator for stuff like that. So me happens is that because i don't want to throw stuff away if i see they're starting to get soft and they're about to turn just put the whole box in my freezer and later. I put them in a smoothie. I'll put them in my kids. Gluten free pancakes this morning. We had raspberries in them yesterday. They had blueberries and so you don't waist 'em they get used for something else. So that's the first thing it'd be reminded of stuff like this. Yeah just pop the whole box in your freezer and then you can put them in a smoothie another day. You know it doesn't matter the solid and so the next thing is fast. We talked about fish oil. <hes> i think everybody knows right. That fish is good for you. The omega threes in them cold water fish especially like salmon and halibut and sardines <hes> have a great amount of omega threes omega threes and the right ratio six our body are anti inflammatory and again then we don't want an inflamed brain or heart or any of the above you have to beware though a farm farm raised fish because really is pretty gross. Yeah non-farm raise fish wore something that's sustainably caught. I'm into that now so i will only buy sustainably caught like sardines because you don't these people fishing stuff out there and they're killing dolphins and all sorts of other just to get their going to send to you. My dad loves sardines. You love your sardis. Love him anchovies too. Yeah i do but those aren't things you can eat all the time. They're so assaulted like i'll take him on a salad any day. The we yeah tumor we talk about the curcumin lloyd's in there. I prefer just to supplement with because most people aren't cooking with tumor. Everyday leafy leafy greens eggs. I think the biggest thing is pastored eggs because the choline which is in the yolk do not eat only eight whites yolk. You need a coaling. There's actually a big epidemic in in vegans having low choline right now because i heard about that you need for your brain. It's super important so we're halfway through the dark chocolate dark chocolate to dark chocolate leafy greens eggs. Make your produce out of the plastic bag and store it out of the bag so doesn't go rotten and if you don't use the bag don't even put it back to begin with there. You go and throw in the freezer if you can't get to them. Save the money and the fruit so absolutely always great jill lane. Thank you so much. What a fun show. Thank you. Thank you everyone one for listening. I hope you enjoyed it. You know what you get one body. You get one mind and you got one life. Get out there today and have some fun.

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You're Being Royally F*cked by Irresistibly Convenient Invisible Radiation [EMF*D Book Review]

Limitless Mindset

1:28:11 hr | 8 months ago

You're Being Royally F*cked by Irresistibly Convenient Invisible Radiation [EMF*D Book Review]

"This is Jonathan with limitless mindset. And this is my deep dive book review of E. M. F. by Dr Joseph McCulloch in this book view. I'm going to explain how and why you're being royally fucked by ear. Resistible convenient invisible radiation. Excuse my French there so you are definitely going to want to check out this book review. Check out the article that is linked below. Wherever you are listening to this podcast in that article. I have links and references to all of the science that I'm going to discuss here. I link out to all of the preventative measures that you're going to want to consider and in this article. I've also got a lot of cool diagrams and graphics that visualize all of what. I'M GOING TO BE DISCUSSING HERE. So perhaps you've had some discussions and Debates ABOUT EMS WI FI and five G. With friends and family. This article with its visuals is going to give you some ammunition to bring to bear in those debates. So let's get into it. You've probably heard before that the ems from smartphones Wifi and blazing fast five G. Networks are dangerous to your health. You've also probably heard that this is just a crazy conspiracy theory. And that all this wireless radiation is fine. Em eft thoroughly breaks down the real science on this controversial issue. It's the latest title from Dr McCullough. Who is a titan in the health freedom movement which is what? I'm all about first of all I want to address the quote unquote skeptics. I so there might be some skeptics out there that are saying to them selves. Wait a minute Jonathan. Cell phones causing brain cancer. Hasn't this notion been thoroughly debunked along with Chem trails? The Flat Earth Movement I to Scientific Authority on these kinds of batters. I believe in science if it was really bad for us if there was really a problem with the F. send all the Wifi in the five G. If this stuff was really bad for us there would be credentialed scientists on the nightly news letting US know warning us. Well if you're a skeptic with those sorts of sentiments first of all I just like to thank you for even considering the arguments against ems and five G. too many people out there who think of themselves as skeptical in rational just mindlessly except what their television tells them to convince them to buy a product. And I WANNA make a couple of important points here first of all if you're a respect her of science you should definitely read this book because it's full of science. It's a very thorough documentation of the significant body of science that underlies the threat to our health. Second in last year an experienced scientists yourself evaluate contentious issues vaccines climate change etc. I with critical thinking about human nature and economic incentives and then look at the science. I'm actually going to repeat that because it's a real important point unless you're an experienced scientist yourself evaluate contentious issues. I with critical thinking about human nature and economic incentives. And then look at the science. Here's why science is corruptible. Scientists are more like politicians. Then they are like priests. You'RE GONNA to check out the podcast that I also did of the book. Rigor mortis where I explain this a bit more in depth and I do link to that podcast in the article and this is because of the perverse incentives that of the of the system that many of them have to operate in. You shouldn't place UNQUESTIONING FAITH IN SCIENTISTS. You can read scientific papers on pubmed but understand that. There is a huge massive nose to signal noise verse signal issue in science the federal funding of science to the tune of thirty billion dollars in the United States alone. Turn Science into a very political game. Unfortunately a lot of science is tantamount to a propaganda article published in Pravda. The Soviet Union's state run newspaper. You'll need to be very adroit. With science to differentiate between real science and propaganda masquerading as science. You'll need to read long boring studies and pick out potential heirs in their statistical analyses. And this all assumes that the scientists publishing paper aren't simply lying and fabricating. Their data thirdly industry funding of science is also problematic because corporations fund science to make money not for the public good. You may not be able to scrutinize all the myriad data and evidence supporting scientific claim but you are capable of asking Cabo Bono asking who benefits here if there are big. Greedy corporations funding science that will result in then millions or billions of dollars. You should be very suspicious of that science if there is science done by scientists who don't stand to gain much that's a lot more credible on almost any contentious science issue you can ask which side is going to profit. A vast fortune from winning this debate and which side seems to just be more consumed more more concerned with human wellbeing and then fourth final point here. A lot of naive people think if something is really bad for us then they would just tell us about it on the nightly news or naive people think that a simple google search or a wikipedia article will reveal the truth again. You have to think about the massive economic incentives. The mainstream media makes billions in advertising revenue from big telecom as do Google and the rest of big tech. Wikipedia is a little more independent but they enjoy a very privileged position with their articles appearing in the most authoritative position in Google searches. So we appear is not going to allow articles critical of big telecom to achieve prominence. If you're still skeptical of the danger of ems consider that quote. The most consistent voice of reason has come from the scientific community in two thousand fifteen one hundred and ninety. Umf scientists from thirty nine countries issued the International EMF scientists appeal to the United Nations calling for the WHO to adopt more protective exposure guidelines for non ionizing electromagnetic fields imas in the face of increasing exposure from many sources. And that's from page seventy nine of the book. Here's why smartphones are the new the new packs of cigarettes. The book begins with an apt comparison between smartphones and cigarettes crew. Although the tobacco industry managed to escape liability and major regulation for more than four decades. Eventually its stranglehold on. The American public came to an end. It's seems that the wireless industry has carefully studied the strategies. The tobacco companies used to deny the health risks associated with their products for more than fifty years. Sadly smoking and cell phones have more in common than their popularity. They also share the fact that they are each and enormous threat to individual and public health. The danger of cellphones doesn't come from the cell phones themselves but from their electromagnetic fields otherwise known as ems. These ems have demonstrable negative physiological effects. But very few people fully grasp this we have been lulled into a false sense of security by an that is going to great lengths to keep us in the dark just like in the early days of smoking and this. I found amazing the trillion fold. That's right trillion fold with t increase in ems crew. The truth is we are exposed to one billion more. Ems Now than we were just one hundred years ago in case you were wondering a billion billion is ten with eighteen zeros. Wow that's a lot. Your body was never designed to be exposed to these levels of it takes thousands and thousands of years for evolution to do its work and for humans to adapt to changing environments. One Hundred Years in evolutionary terms is not even a tiny fraction of the time required to adapt to this type of exponential. Change the US. It is perfectly reasonable to suspect that there will be some health consequences from persistent exposure to this level of radiation. Here's why EMF's are dangerous. And I've got a real cool diagram to go with this quote. The broad strokes of how ems do damage is that they release excess calcium into your cells which then initiates a cascade of molecular events that ultimately result in an increase in free radicals these highly reactive molecules. Then proceed to travel and do damage to your cell membranes. Proteins might have Andrea and stem cells. And not only your Mitochondria but also your nuclear DNA part of the reason why. Emf's are so dangerous. Is that like xrays. They are invisible silent and odorless in less U. R. E. M. F. Hyper sensitive. You won't see feel or hear your ems exposures. It's e- it's very easy to convince people that pollution sharks or even falling coconuts are dangerous because we see them whereas emf radiation is invisible out of sight out of mind right. Encourage your EMF brainwashed friends and family to go. Watch the excellent. Hbo Series The recent series that they did on Chernobyl to remind them that invisible radiation can and does kill. Let's talk about. Emf's verse Mental Health. Mental health is at an all time low while ems at all time high. Do you think that's a coincidence? Crew another vital part of your body that has a high density of vg C. C.'s. And thus a significant vulnerability to ems is your brain but exposure to electromagnetic fields can affect your brain in other ways that are far more common including mental health challenges which have become pervasive and epidemic such as anxiety depression hostility and difficulty concentrating. A two thousand eleven study found that high mobile phone use among adolescents led to increases in Stress Sleep disturbance and depression even US government reports validate the link between ems exposure and mental performance and health. Three government reports have listed multiple neuro psychiatric effects. Let's talk about EMS and infectious bacteria? It appears that cell phone and Wi fi signals could play a role in certain types of area in the case of this study E. Coli and Listeria became resistant to antibiotic treatment. Let's talk about. Ems and autism a number of researchers have found EMF's are quite capable of contributing to autism spectrum disorder to Martin. Paul who's work elucidated the molecular mechanism of how EMF's damage. You suggests that the dramatic rise in autism rates is probably caused by EMF exposure and that would make sense back in the day when we had almost no EMF's when the ems were you know a trillion fold less than what they are now. Autism was almost nonexistent. Ems and leaky gut similar to how ems degrade your blood brain barrier. They also weaken the integrity of another important barrier. Your intestine ems weakened the tight junctions between the cells that line your intestinal tract creating a condition known as leaky gut. Ems verse infertility. In fact at least six. Meta analysis that evaluated more than two hundred separate studies have determined that cell phone radiation is indeed significantly harmful to sperm if the reduction in fertility rates is a result of EMS EMMA. Emf exposure continues to increase as it very well could with the introduction of the five. G. Experiment Ems could serve as a potent existential threat to very existence of our species. Not only will we have an impaired ability to reproduce but the children conceived at this time will face the very real vastly unknown risk of the outlined in this chapter as well as autism. Ems and heavy metals. The research of Dr Yaldo. Schalke Amirah a prolific medical researcher and educator and member of the Alumni Council of the College of Physicians and Surgeons of Columbia University. Shows that the more. Your system is contaminated with heavy metals. Due to things like having silver amalgam fillings eating contaminated fish living downstream from coal burning power plants and so forth the more your body becomes a virtual antenna that concentrates radiation making it far more destructive toxic heavy metals and. Emf's are a match made in hell. You'll want to check out the review. I also did a podcast of the book food. Forensics by Mike Adams and in that podcast I break down the steps that really all of us should take two to key late ourselves to detox heavy metals especially more relevant as we just exposed to more and more of the EMS and finally I want to mention ems and honeybee colony collapse. You've probably heard of this. There was a excellent documentary film. That a lot of us saw about it and I will in fact link to that documentary in this article so you can go and check it out again. Ems are believe to have a major role in colony collapse disorder the widespread collapse of bee colonies around the world. You may find it. Damn near impossible to convince people that their seductively convenient smartphones. Wi Fi and five g. are hurting their health. But they'll find it a whole lot more plausible that all this radiation is hurting the fragile little B.'s. That we rely on for much of our food. And so you can ask them. Should we Zeno side the honeybees with global five g? Because you want faster. Internet or more can we maybe let the honeybees survive and you can wait the extra three minutes that it takes to download a movie next. Let's talk about why. Ems Equal DNA damage and got another cool diagram to illustrate this quote. I is ING. Radiation can also cause DNA damage. This is an undisputed fact. And explains why anytime you have ever gotten an x Ray. Which is a form of ionizing radiation? You have likely been given a protective lead apron to cover your torso and shield your organs. Organs from exposure one of the most concerning aspects of this process is win the ising radiation passes through the nucleus of your cells. Where most of your DNA is stored. It has enough energy to directly. Break some of the Ku Vaillant bonds in your DNA. This is the way that I anais nizing. Radiation Causes Genetic damage which can lead to cell death or cancer. Non ionizing radiation from your wireless devices. Actually Creates Carboni. Ill free radicals instead of the hydroxyethyl radicals that I and nizing radiation gives rise to that 'cause virtually identical damage to your nuclear DNA cell membranes. Proteins mytalk Andrea and stem cells. And this point kind of gets to the crux of some of the debate. That goes on around this issue where people will say. Well you know the cellphones. The five g. The WIFI all. That stuff is fine because it's non ionizing. It's no problem. Oh and in fact the non ionizing itself does 'cause the free radicals that can do a lot of damage the German EMF researcher friends. Abby Cofer used a cornet assay which is a very sensitive test for DNA damage in a two thousand eight study. He found that very low intensity umf exposure at a one point eight gigahertz produced large numbers of DNA breaks. It actually produced more DNA damage than one thousand six hundred chest xrays. Wow that's amazing. I think I've had maybe one or two chest xrays in my entire life so so phones cause cancer a breakdown why a division of the World Health Organization began a tenure. Thirty MILLION DOLLAR. Thirteen country interphone study that looked specifically at the effects of the radiation emitted by cell phones and its potential role in the development of brain cancer. When the interphone study results were finally released years behind schedule? They appeared inconclusive. They found no overall increased risk of brain tumors for cell phone users. Something that most of the mainstream press latched onto win reporting the findings however the Study Group did acknowledge that heavy users quote unquote heavy users of cell. Phones had an approximately eighty percent increase risk of Glioma a life threatening and often fatal brain tumor after ten years of cell phone use and what was the definition of a heavy cell phone user. It was two hours per month. So you have to ask yourself. Do you use your cellphone for more or less than two hours per month. Well that really kind of changes. The conclusion that we can reach as a result of this thirty million dollar ten year. Study doesn't okay. They found that tumors were most likely to form. In the area of the brain closest to where the cellphone rests. While on a call and that risks of developing malignant brain tumors spite in association with three risk factors and. That's the number of years of total use total number of of use and age at first use and then a two thousand sixteen Meta analysis of forty two studies that included more than thirteen thousand women with cases of breast cancer found that exposure to e. l. f. e. EMS is associated with breast cancer especially in the United States the first step to mitigating this risk. That we can all take is to use headphones or the speakerphone function on our cell phones for calls over a few minutes long instead of just holding the phone up to your ear. I think about in the past. I would make a lot of phone calls while I was driving around in my car and I would do the thing where I would. Just put my. I would just jostle my phone in between my ear and my shoulder I would just hold by shoulder kind of up to my ear and I would have my phone just kind of tucked in there while I was talking to people and and driving and I was at increased risk for not only brain cancer but also a horrific car accident. I'm sure so. Just get in the habit of using headphones of plugging in those little headphones into your phone. And then doing your phone calls that way. And since I've been reading this book I have effectively trained by wife to do this to she used to carry on these long phone calls for hours and hours and hours talking to her friends just holding her phone up to her head but she has switched over to using the earphones instead and. I am very happy about that. It's something we can all do. Next let's talk about. Emf overdose symptoms the two most common telltale signs that you're getting blasted with too much. Emf radiation are. Tonight is and problems sleeping. The book explains Interestingly Humming or ringing in the ears is one of the most common symptoms of those who are impaired by or suffer with emf hyper sensitivity. Ears appear to be highly susceptible to the influence of ems and thus they can be early indicators of EMF damage sort of the canary in the coal mine. One of the most common symptoms reported by people who are experiencing a new. Emf exposure is insomnia. So if you're a person suffering with chronic insomnia chronic bad sleep you really want to think a bit about your Wi fi. You want to think a bit about your smartphone and all those emf's that you are bathed in and the issue with the tonight. Which I'm getting the impression that essentially the tonight is is kind of you. Hearing the EMS and tonight this is really not pleasant and this makes me think of dogs. A lot of people have dogs that we love and our dogs live with us in our houses and dogs. Of course have very very sensitive hearing so if a lot of people out there are experiencing tendinitis as a result of EMS. You can just imagine all the dogs and pets that are out there that are suffering that have no idea why there is this ubiquitous annoying ringing right so you know have a little bit of compassion on our furry friends out there. Let's talk about smartphones versus working memory. You don't even need to be interacting with your phone for it to negatively impact your ability to focus a two thousand seventeen study published in the Journal for the Association of Consumer Research found. That students performed worse on tests of memory and attention win their smartphones. Were near them. Even though the phones were set to silent then if their phones were outside the room the researchers theorized that the more dependent you are on your smartphone. The more working memory it takes up even when you're not directly interacting with it and of course working memory is a really big deal you want as much working memory as possible. All of your problem solving abilities rely fundamentally on your working memory on your executive function which just having your smartphone sitting on the table having your smartphone around you time it's hitting that it sounds like and the best way to enhance your working. Memory is to train it with the dual and back brain game. There's some really good evidence for this that I breakdown in a video that I did about dual and back which I do link to in this article. So you're going to want to go check that out next. Let's look at the five G. question quote five G. Will Ya will require new technologies to transmit and receive signals. This means we are about to experience and explosion in antennas and all the signals from all of these additional antennas and base stations will be layered on top of the emf swamp that we are already swimming in the difference between four G and five. G is the equivalent of the difference between a mountain stream of emf exposure and a vast ocean of it. The book explains the real motivation behind the five G. Rollout quote then. What's the real purpose of five g? This massive build out of small cell wireless infrastructure is to enable telecom companies to beam their signals into homes and apartments without having to install a cable. It's that simple. Maintaining the cabled Internet infrastructure is a lot of work. Think about your encounters with cable. Guys you call your telecom company and they send a grumpy guy out to your house that installs or fixes your cables with five G. The telecom companies get to fire almost all of those guys and just beam the Internet into our homes. It's going to beep slightly more convenient for us and massively profitable for them. Crew Five G. will produce twelve point four trillion in global economic output by the year. Twenty thirty five and produce as many as twenty two million jobs although I would contend that it's going to cost probably a lot of jobs in the long term probably much much more jobs on balance once five G. is up and running. It is predicted to produce two hundred fifty billion dollars annually by twenty twenty five just four providing the service Dr McCullough conclude at its route five G. is about uttering in a new era of computer assisted living as well as what's already been touted as the fourth industrial revolution as every part of manufacturing will be impacted by the adoption of smart technologies. And this is just so stupid in my view during a time of falling global. Iq Why how people while the human population on whole collectively is getting stupider. And I explain this in my really thorough book review and podcast that is linked to of the book at Our wit's end and this is a really well researched well written book. That explains why we are essentially living in an era of idiosyncrasy. If you remember that movie that great comedy movie where the Human Race becomes really stupid because of all the things that are going on right now so in this in this book. I explain that in this. It's so stupid to have a fourth industrial revolution which is killing all all of these jobs that people with say a one hundred or ninety. I Q can do. It's so stupid to have a fourth industrial revolution. Which is GONNA kill all those jobs and create less jobs that only people that have say a one twenty I q can. Do you know while during this period while while we are kind of going into a dark age of decreasing IQ. The elites are pushing madly towards massive technological unemployment. It's a recipe for global civilizational disaster and I delve into that further in that book review so do check it out quote as FCC Chairman Agit Pie said in a September two thousand eighteen press conference to announce the FCC's five G. Fast Plan again. These people WANNA go fast with this. He said we cannot let. Today's red tape strangle the five. G. Future and Dr Martin. Paul said putting in tens of millions of five G. Antenna without a single biological test of safety has to be about the stupidest idea that anyone has ever had in the history of the world. Some places and countries are not on board with big telecoms plan for five G. Global Domination Unsurprisingly Switzerland and Russia to countries. That aren't perfect but it seems actually give a damn about their citizens they are the ones rejecting five jeep next. Let's talk about institutional betrayal. The story of how we got to this point is a story of catastrophic betrayal on behalf of science academia and government regulators from the book. Us Senator Richard Blumenthal of Connecticut said the stark fact is the health hazards are unknown and unstudied and that is a sign of neglect and disregard on the part of the Federal Communications Commission. That seems unacceptable. Were kind of flying blind here. As far as health and safety is concerned take two thousand eighteen for example when at and T. spent eighteen million variety and spent twelve million. Nc Ta spent thirteen million and C. T. I. A. Spent nine million consider. This is only one your. That's in two thousand eighteen alone. Overall the communications `electronic sector is one of Washington's super heavyweight lobbyists. The wireless industry has spun a Web. That embraces Congress- Congressional Oversight Committees and Washington Social Life. The network ties the public sector to the private through a friction revolving door really no door at all. Typically government agencies rely on the research community to produce findings that they then merely evaluate to determine regulatory action and guess who is funding much of the research that determines product safety regulations. That's right the industry's who manufacture the products so the regulating agencies are of course captured? Let's talk about science as marketing by paying scientists directly to perform studies. The industry could hand select researchers who were already biased towards believing that cigarettes were safe so this is going back in time a bit by doing so. Tobacco companies also created conflicts of interest as even impartial researchers can be influenced by the desire to keep their funders happy yet. We know that when it company funds research into its own products it creates a powerful conflict of interest that distorts findings in favor of whomever financed the study throughout the late. Nineteen Ninety S and early two thousands. The industry gave Carlo. This was a lobbyist twenty seven million dollars in funds to pay for research evaluating the health risks of ems and hundreds of conflicted studies were produced during that time. Ironically over the course of this initiative Carlo became disillusioned in twenty seventeen. He admitted in a paper that quote the industry strategy has been to fund low risk studies that assure a positive result than use them to convince the media and the public that cell phones have been proven to be safe even though the actual science proved nothing of the sort. So Carlo grew a conscience apparently I wonder if he found religion or did an Iowa Oscar trip. I wonder what it was that convinced him to Give up the big box and speak a little bit of truth. Bet there's an interesting story there. Hey maybe I could get him on a podcast interview if If perhaps his self driving car has not driven him into a guardrail at ninety miles. An hour tragically tragically. Carlo should take out a large insurance policy. I imagine okay back to the book. One way industry funded studies of ems are problematic from the outset is that they use simulated emf exposures instead of real cell phones. Which is just crazy right. You would think they would use the real cell phones. They do this under the justification of seeking to control variables. But the reality is that a simulated cellphone is far safer than a real cellphone. Ultimately by making science fair game in the Battle of public relations. The tobacco industry set a destructive precedent. That would affect future debates on subjects such as food global warming pharmaceuticals and yes. Ems This a grievous institutional betrayal of the public has a cost to all of us that is not discussed in the book. And I would term. This cost the death of consensus reality to have a functional society or civilization. There needs to be some shared values and beliefs so almost everybody in the society or the civilization has to believe for example that they have to believe in God. They have to believe that stealing is wrong or that. Almost everybody has to believe that human life has value just a few examples and you know in a decent functional society people that were really far outside of the shared values and shared beliefs. Well they would end up being kind of ostracized or they would perhaps even end up in jail without a lot of shared beliefs. It just becomes impossible for a society to work things get tribal and brutal without consensus reality. My God told me in a dream last night that I can kidnap your daughter and make her my six slave. What are you going to do about it these types This is the type of tribalism. This is the type of superstitious irrationality that arises when a society a country civilization loses the consensus. Reality it's really not good and I will quote from my article. That goes a little bit deeper philosophically into this. The article was entitled doubt. The devil doubt everything in the past fifty years or so. We've seen a great secularization of the intelligentsia of society increasingly those heading. The most prestigious of institutions are non-practising or non religious. I've been very religious and very secular in mind life and it does change. Your mindset out contend that secular institutions are much more susceptible to corruption. Because as a secular person there's no real downside to corruption and cheating as long as you get away with it. Secular institutions will inevitably devolve into a Darwinian ends justifies the means struggle for resources power and prestige genuinely religious. People have a very different kind of motivation. They seriously believe they will face judgement in the afterlife for their misdeeds in this life sure there's plenty of religious people that have done bad things but if you've known as many religious people as I have and an equal amount of secular people. You know that there's a big difference in trustworthiness religious people believe either metaphorically or literally that the devil is at their door knocking. They are fearful and importantly avoid. Didn't of temptation that will lead them to greater sin. Unprecedented numbers of people. Now believe in the flat earth or that we never went to the moon. You'll want to see my podcast where I comment on that. For example and unprecedented number of people now believe these sorts of things because bad science and corrupt institutions have broken. The public trust too many times because they want to make a buck. Humpty dumpty cannot be put back together again we're now reaching the point where significant swaths of the population especially in America. Just don't believe and would actually oppose perhaps violently the official line coming out of the government or scientific authorities. This is an untenable state of things. The elites in science and government should look themselves in the mirror and take responsibility for breaking consensus reality but they probably can't even see their own reflections moving on a breakdown the EMF protection life hacks. So there's a lot of bad news up to this point but there's some good news which is that. There are a few ways to mitigate and manage the toxicity of ems. I'm not asking you to repent from your sinful smartphone usage or US swear to never use Wifi again in less you go resettle in the absolute middle of nowhere and live as a disconnected hermit. It wouldn't help that much because we are surrounded by other people using smartphones and most of the buildings where we spend our lives are flush with Wifi so my wife once told me Jonathan. You know you shouldn't eat before bedtime and I sort of shrugged it off because for years. I've been doing a little snack king before time. Nothing egregiously unhealthy usually some organic crackers with tasty PESTO OR SESAME. Tahini and I've always had a very lean physique. It didn't seem to result in me gaining much weight. I do regular intermittent fasting. I don't eat anything until I have a late lunch in the afternoon so I figured that the snacking was fine. I thought that don't eat before. Bedtime was one of these over simplified health. Tips like salt is bad for you. That came out of the crappy mainstream nutrition science of the Eighty S and ninety S. Well it turns out that my wife was right. She's a smart lady. She has some real good instincts. Emf explains why it's especially good advice to refrain from eating four two four three to four hours before bed. Give it three to four hours. Here's why fortunately our bodies have a system to repair damaged DNA and it is called the poly. Adp BRIBE's Paulie Mariss or pop would just call park from now on and without the park system you would have died of cancer by now because it goes in repairs your DNA. That is getting damaged all the time by all sorts of things when ems or radiation from a leaky old microwave. Hit Your DNA. It's the park system that comes along and repairs it and got a cool diagram of this in the article but importantly park needs fuel to do its thing and that would be the NASD P. H. Molecule. Which is downstream of the well known entity plus molecule. The book explains if you eat a large meal close to your bedtime. There is simply no way for your body to burn those calories as energy so it must store the calories by creating fat. This process consumes enormous amounts of any DP with your any peach levels. Lowered this way. You will be unable to keep your antioxidants optimally recharge while you sleep. As a result you will have four more oxidative damage from the free radicals that kid be neutralized do too low any Ph levels than if you had eaten those calories earlier in the day so eating before bad costs any Ph that could be used to repair DNA damage but your metabolism is first in line to use the NASD PH. Evolution didn't predict that we would have wireless Bluetooth smart watches and Alexa devices so often there's not enough gas left in the tank for Perp to repair our DNA. Nightly if you righteously bang your wife like I do she. She deserves it for all these good little health tips that she gives me or if you are doing something else that. Burns a lot of calories right before sleep. It might be okay to indulge in some late night king but if you're just going to lounge around and watch TV as most people do your body has to put those calories into storage converting them into fat costing any D. P. H. A little fat isn't going to kill you or make you fat as it didn't with me but if you're concerned with em talk and you don't want to give up the convenience of all those marvelous wireless gadgets. It's smart to give up late night snacking. Eat a filling dinner at like eight. Pm and then go to bed at midnight next life is to turn off your Wifi at night. The next impact. Full Life Hack. That doesn't require any. Sacrifice is turning off your Wi fi router at night especially if your Wi router is in your bedroom you are being irradiated by it all night as you sleep. And that's the one time of the day that you definitely don't need Internet access if you sleep for about eight hours at night and turn off your Wi fi you cut down your emf irradiation from the y five by thirty three percent more if you turn off your Wi fi a little before bed as I do. I recommend an Internet fast for at least an hour before bed during your Internet fast. You want to do some things that are just a little bit lower stimulation so that you can get. Your nervous system turned down just a bit more so that you can get some really great quality sleep so for that hour. You're going to want to do things like reading or meditation or having a conversation or righteously banging your wife. The book explains how this helps function minimizing. Your emf exposure can radically increase your any D plus levels because when you're exposed to ems and your DNA strands. Rake Park uses between one hundred fifty to two hundred molecules of N. Eighty plus in an effort to repair that damage. You'll also probably notice that you sleep better with your Wifi off. As insomnia is one of the most. Common Effects of EMF irradiation the life hack for this is to connect a power outlet timer to your Wifi that Jus- cuts it off at eleven pm. Or whenever and you could install an APP that automatically puts your phone in airplane mode at the same time. I don't have one of these so I just switch off the power router connected to my Wifi router and my laptop win. I'm done working in the evening so by all means in the evening. Turn off your Wifi and turn on your wife fee. I do next. Let's talk about supplementing. Any plus the next crucial bio hack for fortifying your biology against ems is to your park system. Extra fuel supplement a bio available source of energy. Plus which your body converts into much-needed NAACP H from the book. Emf exposure can cause your cells to become anyplace pleaded. Pope is ordinarily the largest consumer of entity plus in your body and if you have a large m. f. exposure you can radically reduce your energy plus levels and win your cells become any plus depleted it also impacts your mind cadre by lowering an any Coenzyme called N. A. D. H. Which is necessary for your Mitochondria to produce a t. p. and another consequence of park sucking up most of your entity plus is that it depletes the supply for other vital longevity protein called. Sir Tunes that require any D plus to function. If Park is consuming. Most of your eighty plus your cer- tunes will not have enough any plus to run and your aging will be accelerated dramatically so not only does your DNA repair system get screwed by EMS. Your Sir two wins the light switches of the genomes due to unless you want to give up technology you need extra eighty plus in your system supplementing. Any deplace itself must be done via injection at a special clinic which runs about six hundred dollars but fortunately several precursor supplements are well studied affordable and safe first of all vitamin B. Three also called. Niacin is a deep supplement but many steps removed from the any plus molecule. You get less any D plus bang for your buck from Niacin and it causes a skin. Flush which many dislike according to the book though as little as twenty five milligrams daily is an effective preventative. Measure and the non time released. Niacin is better. Secondly nicotinamide riboside is two steps removed from any D- plus it's well studied and demonstrated to boost anyplace in clinical trials. And then thirdly an am an this is nicotinamide mono nuclear tied. This stuff is one step removed from an eighty plus so it's more bioavailable and activates the ser- to insert three while and are the nicotinamide. Riboside does not is pricier. But I think the best option at the NASD plus supplementation gas station and the N. R. And the men are mentioned in the book itself. I'm going to do some experimentation with the vitamin B. Three with the NIACIN. Want to see if the twenty five milligrams that Dr Merckel talks about of niacin produces that unpleasant skin flush if a smaller amount doesn't have that effect then I think it's actually a pretty good option especially for people that just can't afford an as it is definitely pricier and vitamin B. Three Slash Niacin has the advantage of being available almost everywhere even here in Bulgaria. I have seen Niacin at a number of pharmacies whereas is pretty tricky to get my hands on in in in lots of places if you live in the United States if you live in a quote unquote first World Western country. You'll probably be able to pick off. Pick it up off Amazon with no problem but other places as Niacin might be a better option in the article. I do link to the best source of that. I have identified with something like an men because it is pricier. You Really WanNa make sure that you're getting the real thing you really. WanNa make sure that you're getting pure an an and I have identified a source that does proper spectroscopy testing quality assurance testing for the purity of their an amend and importantly it is done at an accredited American laboratory. If you're GONNA spending this kind of money on supplements you really want to demand a CEO. A that is done by an accredited American laboratory to make sure that you're getting the real thing. Moving on a mention supplementing molecular hydrogen and this is a supplement that has a powerful antioxidant effect counteracting. The reactive oxygen species that are overproduced as a result of EMS doctrine. Mccullough speaks very highly of it. The next supplement worth mentioning something that we're already well acquainted with magnesium. There is one more supplement strategy to address. Emf damage that can be effective to block. Excessive calcium channel activation magnesium can help with this magnesium is the fourth most abundant mineral in your body after calcium potassium and sodium. It activates more than six hundred enzymes and ease important. Cofactor four the activation of a wide range of transporters and enzymes and something else that eager to try is blood flow restriction training exercise. Dr McCulloch describes it. If you fail to exercise regularly as you age and grow old not only will your entity plus levels drop. But you're nicotinamide precursor levels will rise high levels of nicotinamide in turn will inhibit the ser- to in longevity proteins. So you should engage in some type of daily exercise and sleep consider blood flow restriction training that he describes a little more blood flow restriction training that allows the use of low weight and high repetitions to produce incredible metabolic benefits including NAM PT Activation. It is my absolute favorite way to increase N. eighty plus not only. Will it increase any diplomas? But it will also prevent treat circuit or age-related muscle loss. And Osteo Perot Service and I link to a more in-depth video that Dr McCulloch did on his own youtube channel about it. The blood flow restriction training. Seems like a real smart idea that the sapient bio hacker will want to just make a regular part of their life next life. Hack you WanNa keep some distance from your phone quote if you have a cell phone signal even if you aren't using your phone at that moment or don't even have a cell phone. You are being exposed to radiation when you begin using the phone and hold it close to your body you are being exposed even more so make a bit of an effort to keep your smartphone if it's not in airplane mode to keep it on the other side of your desk or if you're sitting at a table eating and you're not using your phone try to keep your phone on the other side of the table. A tablet tip unlike computers. These devices tablets are often held just inches from users face where the radiation exposure is exponentially higher than win. It's an arm's length away as with a desktop or laptop computer. Now I turn off the Wifi Bluetooth on my ipad while I'm using it most content like kindle books that you want to read on your tablet tablet you can download and then consumed with the Wifi off. And there's probably some of you out there that read my articles on medium so it might actually justify paying for the medium a premium service. I think it's maybe fifty dollars a year or something like that. Go in pay for that service because then you can download my articles. I don't know why you would wanna read anyone else's articles on medium. You can download my articles to your device and then just switch off your Wifi and enjoy those at your leisure. Emf free. When I watch v