Episode 110 : Tommy Wood talks about nourishing developing brains and the importance of metabolic health

Automatic TRANSCRIPT

Welcome to stem talk. Stem 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 on Carnegie and joining me to introduce today's podcast as man behind the curtain Dr Ken Ford, Agency's Director and chairman of the Double Secret Slice and committee that selects all the guests who appear on stem talk. Hi, Don. Great to be here. Our guest today is making a repeat appearance on stem talk Dr. Tommy, would a UK trained physician who is now a research assistant professor of pediatrics in the University of Washington's division of neonatologist he was our guest on episodes forty-seven in forty when we did a two part interview with Tommy. So back in February Tommy a very popular talk Jim sees lecture series about the components of building and preserving brain health across our lifespan, and so the double secret session committee thought it would be a great idea to have him back on the show and his lecture Tommy touched on ways that we can maximize health developing brains things we need to consider if we suffer from an acute brain injury and also how to maintain a robust brain for decades as we age, and once again, our conversation Tommy was so long and wide ranging that we have against split his interview into two parts. So in today's. Episode we'll be talking about the importance of metabolic health especially as a way to protect ourselves from covid nineteen we touch on Thomas work at developing accessible methods to track human health and longevity, and also his research as an assistant professor of pediatrics at the University of Washington where he studies ways to increase the resilience of developing brains. In part two of our interview, we talked to Tommy about his continuing research into lifestyle approaches aimed at improving health span N. lifespan, as well as physical performance. We also have a fascinating discussion about the physiological and metabolic responses to brain injury and their long-term effects on. Brain health. So. If you listen to our earlier interviews a Tommy, you might remember that he received an undergraduate degree in biochemistry from the University of Cambridge before obtaining a medical degree from the University of Oxford. After working as a doctor in central London, he moved to Norway for his PhD work and then to the University of Washington as opposed sock alongside academic training Thomas Coach. Athletes. In. A. Multitude of sports anywhere from weekend warriors to Olympia NHS world champions his outgoing president for the Physicians for Ancestral Health Society a director of the British Society of lifestyle medicine and sits on the Scientific Advisory Board of hints that performance which includes developing performance optimization strategies for Formula One drivers, and as if this isn't enough Tommy to do he's also visiting research scientists here at. So. As you can see, we covered a lot of ground with Tommy. But before we get to part one of our interview, 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. As, always, the double secret session committee has been continually and carefully reviewing I tunes Google, stitcher and other podcasts APPs for the wittiest MS lavishly praised filled reviews to read on stem dog as always if you hear your review, read on sometimes just contact us at stem talk at IHS dot us to claim your officials them talk t shirt today are win review was posted by someone who goes by the moniker win Sir Four. The review is titled Brain Candy for Science Junkies. The review reads. I i. Ran Across stem talk when I was checking to see what was up with Dr Peter Attiyah, I ran across the very first podcast by stem talk I immediately subscribed and took a deep dive into the archives a WHO's who of names I could not wait to hear I was suddenly lost to my wife for several days is I binge listened to many if not most of the episodes while doing yard work, this kept me from being accused of antisocial by wife. In made my property look better than ever for those who complained dawn in Ken, our scripting to me it shows preparation and for that I'm grateful. Well, thank you so much for Windsor for anytime we can help them what their spouse family or friends were definitely more than glad to help and you have given our listeners another reason to tune to some talk it can not only improve your brain, but also your yard so I'll have to take that into consideration as well. So that was a great review wasn't again yes it was and we really appreciate all of these wonderful reviews and now unto our interview with Dr Tommy would. Stems. Stem time talk stem talk. Hi Welcome to stem talk I'm your host on Carnegie's and joining us today is Tommy. Would Tommy welcome back to stem talk. All right. Thanks be back and also joining us is Ken. Ford. Hello. Don. Hello Tommy Welcome back. So Tommy since covid nineteen is at the top of everyone's mind right now. I'd like to start by asking you about. That you a colleague recently wrote an innate you point out that is becoming increasingly clear that underlying conditions associated with sub optimal metabolic health appear to be associated with poor outcomes in patients with covid nineteen, and considering the nature of these underlying conditions that include obesity and hypertension. You argue that lifestyle based purchase to protecting ourselves from covid nineteen are to be one of our best tools in addressing this ongoing pandemic as well as in future pandemics. So can you give our listeners a summary of the key points that you made in that article which is Great. Article by the way show. Thank you. This is a an editorial I wrote for a new journal called lifestyle medicine with a friend of mine and colleague Government Johansen. He's an Er physician in Iceland and he has an increasing interest and expertise in Imia metabolism. So the sort of intersection between metabolic health and immune function, and if you look at pretty much any data source that's currently available this suggestion that those with beastie metabolic disease, those conditions that you mentioned, they have a worse outcome in impatience with Covid, nineteen and if you look at previous, let's. It's been less widely publicized, but you see the same thing for various strains of flu h one n, one swine flu, as well as previous saws and Moore's should occur viruses sort of preceded sauce Kevi ends. In people who have disease as well as with aging you see this change in how the immune system function. So you have don regulation of the adaptive immune system changes in t cells. Cell populations decrease and you also get a relative increase in the activation of the innate immune system, and what happens seems to happen is that you get a slow initial response to an infection amounts of proper response to clear it. But then later you get a much larger sort of compensatory response to the virus. And this may be part of the sites kind storm that we hear about, which often happens as a second phase of the disease, and so this happens in disease and those a group who have significant expertise in bottled to age also a paper or is currently pre print talking about Kobe nineteen as an emergent disease of aging and changes kind of converge in metabolic disease, an aging, and so in this paper or or editorial we we make the argument that if you want to prepare for future pandemics, obviously, we're thinking about a vaccine development testing through having a pipeline to respond to whatever the the future pandemic going to be an some. People think it's most likely to be a strain of flu rather than a corona virus on top of that, you need to try an improve the metabolic health of your population. If you want to maximally reduce the morbidity and mortality, we talked about lifestyle medicine. That's kind of the current best accepted term that covers the idea that sleep stress and movement and social connection all those a key to health lobby about Las Islas on the podcast, and we certainly not the first people to say this. This is this is definitely become more and more publicized that these metabolic diseases are associated with whereas outcomes and found interesting because it's been some pushback by. Other people who say that it's targeting or discrimination against those I would pull health but but that's certainly not the goal and when this comes out, the be an accompanying editorial by the editor in chief who says, the messages is actually quite pulsing I believe that's the case. There are a huge number of tools and strategies many of which we'll talk about today I believe you can use to improve your metabolic health and I think is really important to be agnostic to those tools because so many people have different things that they want to do or the they might want to change improve the health and as many things they can do. To, do that and one problem with lifestyle medicine is in the US. Particularly it's associated with the American College of Law Madison, which is very dogmatic awards plant based Diet So so we make the argument that they're actually a wide range dot was it always comes down to thoughts rewards, but we argue that there are multiple different ways to skin this cat and we should be to that and have all those options open. However to make this, happen I, think we need a better combination of digital health tools and better education and implementation healthcare system. So at will require some some kind of significant investment process to sort of get these ideas. and. The help to the people who need it. As part of this future pandemic preparedness as we called it. Makes Perfect Sense. So Tommy when we interviewed you a few years ago, you'd just become a senior fellow at the University of Washington and we're in the process of moving permanently to the US and when we asked what brought you to the states you said in the Sa-, quote a girl. Well, we know that you ended up marrying that girl who turned out to be Elizabeth Nance. Who is Clare boothe lose a assistant professor of? Chemical Engineering at Washington, and we interviewed her on episodes of one of some talk love that stem talking of you as well. In addition to you guys getting married you've also written papers together. So is it safe to say that the two of you get along really well because a lot of time together from professional to personal Yeah. Yeah we we do. Absolutely. We get along very well as hopefully expect. So yes since since master. Bad if new woods didn't get along. Together. Yeah. It would be bad. So so luckily, none of that but this is since those lost on stem told we got married we've published if you pay together submitted several grounds together so I can safely say she's my most important collaborator and pretty much every area of life I love that. So congratulations to you guys as well. You know are a research assistant professor of pediatrics at the University of Washington in the division of neonatologist, your focuses on ways to increase the resilience of developing brains really interesting important, and you also look at ways to treat neonatal brain injuries. Can you give us a quick overview of your work and then we'll talk about some things more detail. Yeah, absolutely. So the majority of my academic work has focused on investigating how Nina the brain response to injury, and then waste treat those injuries and most of this, I do and models and one strength of the neonatal brain injury field that I really like is there was a wide range of complementary animal models, which we can then use to find a treatment or examined process across all species before we try and translate it to humans I think that's lacking from from other areas of Jewish science like we talked about last time most of. My work is focused on developing ferret models of brain injury, and now we have successfully developed a wide range of reproducible models that really depend on my life period or the type of injury that won't study. So he can premature birth we can look at brain injuries at full-term. So Paranoia succeed problems during childbirth all we can look at pediatric adolescent traumatic brain injury and as I spend more time working in these areas, what's become really interesting to me is how these things by interacts over time. So what happens if you're born prematurely and get? On a football field twenty years later or does your early life brain injury ulcer susceptibility to two things that might you might be exposed to later in life like your diet or if you're an athlete and you get a concussion, does that change you'll? See to another injury later or if you're exposed to HYPOC, Sierra shoot you then more or less susceptible and these kind of questions I really hope to dig into the next few years. Fantastic Tommy and so when you give talks, you'll often start by giving a disclaimer which says, many of my best ideas are stolen. Like so when you're looking for ideas, what are some of the best places that you like to visit? Yeah. Yeah that's true. I think of when I spoke. Recently accidentally said that most of my idea is a song which. Is True. There's a slip at the time. I try not to actually steal and with much give credit to the people who inspire them in a hope unusually successful at that. But I'm I'm really lucky to have a rich network of friends and colleagues the approach problems in different ways. So the first thing I do is trying to make sure that I learned from each of them as much as I can i. will try read quite broadly because you never really know where inspiration is gonNA come from. But at same time, it's also important to realize that whatever bright idea you think you had has probably been hot by several people before you You know as they say this, there's nothing new under the sun and I think that's just a of life. This is one reason I. Really. Enjoyed delving into the literature from several decades ago I think there's a huge amount of impulsive physiology she work that was done in the fifties, sixties and seventies, and the love is really signed to see a revival now but we think is new ideas but she people were looking at a long time ago I do like to use social media as a tool just to kind. Of follow interesting research because that sort of it's more likely to pop up quickly there but I think it's also important not to fall into an echo chamber of all the people who you agree with on a certain topic. So I try to embody or of the words of Dudley Field Malone who supposedly said, I have never learned anything from any person who agreed with me. and. I don't think that's true all the time but there is a huge amount you can gain just by following people who have different ideas to you downside then is that you have to sift through a lot of stuff that you really disagree with and then not try and mount an emotional response to it but overall I think there's this benefit for that like a lot. So when we interviewed Elizabeth, she said she can't stand to look at your computer because you have so many windows open at one time I have to. Say I'm guilty of that as well. So I feel better knowing that Tommy she said that you're constantly reading paper after paper after paper, and then it makes her dizzy look at your computer screen with all the tabs of windows. So can you talk a little bit about your research methods and how you go about collecting material because in this day and age we know this overabundance of information that are way just being able to sort through everything is tough. So be great to hear how you do that. Yeah absolutely and I learned. Jury my PhD to not. Make myself feel like I have to stay up to date on every topic. Because that way lies just complete insanity. But there is some method to the madness, the disease. So I'll keep tabs and website pages and pages organized by topic in grouped into a process. which anyone time is probably multiple papers, grant proposals to the kind of like groups together. But it definitely looks a little overwhelming to begin with and I did actually have a friend and colleague recently joked must keep my tabs and processes open. It ought to create some additional cognitive load because otherwise I would just be too productive. So that's what does that that. Might be happening. So Salva Israel's to casting, which is a fancy word for random. But. One interesting thing. I've noticed about myself over time is that of changed the way the I sort of engaged my brain to remember things. So if you're a student as an undergraduate sort of had to remember all these, all these facts are you have to be able to regurgitate them in an exam but now I focused less on remembering facts and I remember where the information is. So if I just have a small snippet of an author or title of a paper or something contents, and then I need to go back and get information as much easier for me to find it so I find myself remembering where things rather than what things Make sense and indeed, and that seems to be Remembering where things are seemed free? The current trend is people's heads are essentially empty. Your current research interests, as we've started to discuss, include the physiological and metabolic responses to brain injury in their long-term effects on brain health. In addition to this, you are also working to develop usually accessible methods to track human health performance and longevity three topics of great interest here, and you know it's that's quite a wide range of interests and we'll talk about some of them in today's discussion but out could give us sort of the hundred thousand foot impression of this. Absolutely. This is one of the best parts of my current job, which is that I can essentially work on anything that I find interesting and some point is speaking to come relevant to. All the other things that I do or at least I've seen that happen again and again. So I'm also fortunate that some of my previous work with athletes and those trying to optimize health and performance led me some of my current consulting work, which is where those aspects of tracking health and longevity in an affordable manner scale a happening. So kind of separate to my former Democ work but certainly, quite relevant because when you look at things at the forefront of longevity aging research this could be tracking methods. Oh interventions actually they often become relevant to treating you the needs, neonatal brain or other brain injuries. So I've certainly seen that with keystones and. You know all these other factors that we've started to see become sort of cool in in the anti-ageing space while on the face of it certainly seems like collect a variety of unconnected interests I do think that doing each one me a scientist in the other ones the downside is that this often causes raised eyebrows informal academic circles where you know your junior faculty and you're supposed to only cultivate one area of expertise and if you. Publishing multiple areas they think that that means that you don't know what you're doing, what you want to do or who you are as a scientist but I'm very lucky that the people I work with particularly my division chief at the University of Washington. They have also have very broad range of interests and they see the importance of drawing on multiple fields and I think we're starting to see the benefit in our research in the lab. That's fantastic and so it's kind of going on that theme as a neonatal neuroscientists he work mainly with newborn babies with brain injuries, but you also work with football players and Formula One, race car drivers and work with people with Alzheimer's disease. So those people who specialize in brain research is we've been talking about will pick an area near Natal or timers to focus on you however seemed to be more interested in looking at the brain from cradle to grave in across a wide spectrum of different individuals in different professions and actions. So why is that? So the the simplest ulcers because I find all these things interesting I want to do all of them. But but in reality. I think there's a huge risk in silencing research based on a single diagnosis of disease, and that's particularly true in neuroscience and we look at the treatment of neurological disease a hole. There hasn't been a significant step forward in disease treatment essentially for decades. The last truly innovative thing that came to the clinic was the tripped on drugs for Migraines in the nineties. So between thirty years since we've had true improvement in our treating neurological disease and we're still left with nothing for. Multiple. Sclerosis Alzheimer's disease most other neurological conditions and as analytical techniques improve and the complexity of the information we have increases is very east to just assume that I'll theory or model of a single disease is the right one but we just need more data in order to understand it and I think this is the approach. This brilliant essay that I often rob refer back to written by Uras ethnic in cancer in two thousand and two as called Kepala. Just fix a radio. And he describes in hilarious detail, what it would look like if biologists took the current approach to understand disease and applied it to fixing old broken radio so For instance, this section wet several groups of researchers look inside the radio and they see that transistors, resistors and Pastas, different colors. So they spend their entire career seeing where the changing the color of a resistor affects the way that the radio performs which obviously complete nonsense but this is what I think. We're doing a lot of. With their fiddling with the color of resistors, and then wondering why we can't get the radio to work was colors do mean something. They do mean something but the internal workings don't change. So instead I kind of justify my my broad range of of interests because I think if you're looking at multiple mechanisms of brain injury across the lifespan, you're forced to look for commonalities and themes that give you an overall picture of the system and what the system requires both in health and disease rather than becoming hyper focused on a single mechanism. So I think even more of this to try and find meaningful ounces for those I with neurological disorders, and that's how I kind of tied together all those different periods of life in in different types of injuries to try and find some kind of some kind of commonalities makes sense to me. In the talks you give you often bring up maslow's hierarchy of needs as a way to sort of explain to people what a brain needs. Can you go into that just quickly for our listeners? Yes, I think that's a way that we can best connect or create a framework A brain might need in order to to sort of have long term long some. Health and there were multiple different ways you know theories to do that. But I I use maslow's hierarchy of knees because it was developed to give a you know an overview of the broad range of things. The humans might need for long longtime health sir, Abraham as low as an American professor of psychology and in Nineteen fifty-three published this paper called a theory of human. Motivation, which included this hierarchy of needs which must be will display pyramid. Now I at the bottom, you have physiological needs. So that's food water warmth rest and safety needs. Then you have psychological needs that's blowing this love self esteem and self fulfillment needs of the top, which is things like purpose and achievement and creativity, and it'll be able to debate as to whether. This is really you know the the final framework or whether these things change a time and that really matters because he just sort of gives us an idea to to put together things that might be important. So I've changed it from a pyramid from to a three legged stool for the brain of the things that the brain needs long term health. So those things. That's like and substrates and building blocks like oxygen and glucose security system protection from injury treatment for injury, and then protection against any kind of noxious exposures and then connection, and that's kind of broad, but it can be both between cells, but then also to the external world and having some kind of stimulation to bring all these things together. So as a stool, the idea is that each leg is potentially equally important, and if you're missing one leg, it's a lot harder. To maintain balance on just the other two legs. So I have no idea where this is the best model but I think it's a nice place to start to explain what is a brain needs for optimal long term health spent tastic and Tommy said that you find recent brain age studies to be particularly fascinating because they are just now beginning to show how fetal and neonatal exposures affect adult aging. So can you give us a summary on what these studies are showing us? Yes. This is a relatively new field because rony just now able to start looking at comprehensive data from neonates and how that's associated with outcomes in adults. For instance, the first premature infants who had significantly improved survival they were born in the seventies and then they were more improvements in care in the eighties and nineties with things like fatten and benefit elation. So these these people are only now in their fourth fifty. So only starting to see some of the some of. The signal that but in general people are born prematurely seemed to be an increased risk for almost every chronic western disease. So heart disease type two diabetes, obesity chronic kidney disease, and we don't really know about cognitive decline of dementia Nina exposures such as maternal infection, which could be at your tract infection or the flu while you're in you throw while while your mother's pregnant these are associated with an increased risk of a number of neuropsychiatric disorders like autism and depression. and. When You look at this in terms of aging, we have some data on people who are in Yusra during the Dutch famine during the German occupation in World War. Two. And those people seem to have older looking brains relative to people who are the same chronological age but weren't exposed to that while they were in the womb and there are some small studies show that people who are in their twenties and thirties now and they were born prematurely they show more rapid brain aging and shorter telomeres compels people who weren't born prematurely and and tell them on a great measure of aging but this sort of everything. Seems says look like it's going that direction that if you're born me if you have some of these exposures in the wound than you age more rapidly later in life, we don't know yet whether this is a permanent EPA genetic effect occurs very early on or whether it creates it increases too busy to later things like the environment or lifestyle that then may precipitate faster aging at the same time. If you expose these things in the women you're born prematurely, can we intervene early and then change whether this happens over time and that's something I hopes of myself and my colleagues will help to figure out. The Thomas step back for just a second and talk about what goes into growing a brain, and we know that when we were born brain takes up about seventy five percent of our metabolic rate. So maybe a good place to start is describing the energy needs of our brains wimmer especially in the developing brain. As species, we take a very significant risks to have the brains that we have an and I know you've had Stephen Canadian on the focused previously talked talked about some of this human brain is incredibly complex and very metabolic creek demanding. But at the same time when you bowl and your brain is essentially useless, you ought just like this complete anonymous lump that means that you have to rely on essentially everything from your from your parents whilst this brain develops and that takes a huge amount of time and energy in. The brain. We have to have a very significant energy fuel it which is why humans are essentially the only primate, the half fat babies. This is basically our buffer to make sure there's always energy available to supply the brain. While you know people often talk about glucose being an essential energy source for the brain in reality that stores that be turned into key tons, and then Keaton's also give a very significant proportion of of of the brain's metropolit- needs. Instead the last year he published a paper. About the potential use of exotic key towns for neonatal neuro protection, which starts at the idea of Keaton's being essential for the newborn brain you've been talking about can you talk about the rule of Keaton's and brain development specifically yet S-. So as I'm sure, most of the listeners know that the use of genyk diets exhausts sends a brain. Injury is a very promising active field of research that even you guys are actively involved in if you look at the unites of brain physiology, the developing brain. Will basically take up as many as you'll give it and by motor equivalents at least sixty percent more than than glucose and this relationship is pretty linear. So basically take as much as it can get. That's because in the fetus, and then also after birth and there are two mechanisms that ensure ongoing ketone production in the DNA so that the've your cells in the milk ducts, the mother's breast tissue they actively synthesize medium. Chain. triglycerides from glucose in the blood and those creased into the milk. So after being fed even though that comes with a significant amount of carbohydrate in the breast milk, they have MC tease those will be continuously being abetted in tetons alternatively between feedings or. Part of the reason why we have fat babies because breast milk doesn't necessarily appear immediately or there's GonNa be some time in between those fatty acids are going to be released from the adipose tissue and they're going to be ten key signs and newborn babies and two significant false ketosis essentially in a couple of hours. So in other words, newborns prime freaky tests. Yeah. Exactly. Which is why I'm very interested in key signs in Europe protective agent the baby's brain injury because if any brain is ready to take advantage of the neuro protective effects of keystones. DNA Brian make sense kitone bodies play a major role in the central nervous system during my nation not only sources of energy but also as sources of carbon for lipid bio synthesis, can you talk a little bit about the significance of this and try to tie this together for the listener when I was first looking at Keaton's Phoenix your protection this particular fights With something that was new to me, and actually probably the most fascinating thing that I found an even back in the seventies Hans Krebs who I can whose work. Let's quote as often as possible to can his group described the that Kitaen up taking the developing brain was at least on par with glucose like like I mentioned and they suggested that they provide. At, least fifty percent of the metabolic energy demands of the nie-nieto grain. This has since been revised down to about ten to thirty percent because some slightly later work showed that keystones preferentially used as synthetic Prekaz mainly for the reduction of saturated fats and cholesterol, and so if you want to grow a large brain, you need to make a lot of saturated fat. and. Cholesterol and keystones the main Prekaz for that. So if you think about anything that's not water in the brain about seventy percent of those fats and a significant proportion of that cholesterol more than ninety five percent of which has to be synthesized locally, and similarly about fifty percent of the facts there are saturated. Those also synthesize locally. So if you look at. Rats who are very similar to humans in this respect if you give them Keaton's those keys will preferentially be used as building blocks synthetic precursors to build the brain and then glucose will get used for metabolism. So you're thinking about keystones both in terms at Feldman, and in terms of brain injury is one of the potentially most important aspects. Because if you have an injured brain, you have to repair the area of damage and you're gonNA need new building blocks and everything that we see from the developing brain is the we preferentially use Keaton's to make those building blocks in them. We can use that to repair and Genera that that's the idea. In, addition to key tones, unsaturated fats also play a major role in brain development. Can you elaborate on this a little bit? So when again you're looking at the things that accumulate in the brain as you grow unsaturated fats are a crucial component, and so these are generally split into two subtypes polyunsaturated fatty acids. You might think of the mega threes, Mexico's, and then monounsaturated fats, and basically all the way during development, and then can continuing for years off to buff. There's an a linear increase in these unsaturated fats in the brain. So the most important ones being Dha should a long chain, fatty acid, a racket onic acid along chain of mega six, and then oleic acid, which is a monounsaturated fat and the timing is slightly staggered. So Dha is maybe more important towards the end of pregnancy and then. It becomes slightly more important after birth, but unlike the saturated fats and cholesterol, which is synthesized locally in the brain, most of these need to come from an external source. So they're gonNA come from from the mother from the Placenta during pregnancy or they're gonNA come from the Diet with smoke later on in general, these are GonNa come from animal foods although it is possible to synthesize some of these from short chain mega sixes in the mega mega three with Fahd's. Jeans. But this is a huge potential for diet to them. Play a role in terms of how available these all. So tell me what about what the mother eats. The maternal diet also plays an important role in infant development as Reno, and you've spent a lot of time studying the work of the late Sheila and s who was a tireless researcher and proponent of the nutritional needs of babies, children, and also expectant mothers. So what are your key takeaways from her research? Sheila in a pretty much single handedly pioneered the early research into polyunsaturated fats in the infant brain development including the effects of maternal and the composition of the breast milk. She was originally English. But spent most of her career at the University of British Columbia what I particularly enjoy about how work is the fact that she spanned everything from basic work and cell culture too small and large animal models and human clinical trials, and there's very few people have the skills and the interest to really translate all the way from the most basic research all the way to actually improving outcomes in humans and. Give a little respect for that, and she did a lot of work showing the maternal diet directly affects the fats in the breast milk. So particular when fast makeup significant proportion of the Diet then the composition of the breast milk in terms of fat content pretty closely follows what's in the Diet and about third comes from the recent diet. So what was maybe the day or the day before and two thirds come from adipose tissue, which again is usually stored fat you've previously eaten. So plays a huge role. There I'm one of the main takeaways from. Work for me is the critical importance of Dha. Again, this long chain mega three, fatty acid. She showed that it makes up about ten percent of the fats and infant brain and in insert neuronal sign ups is the right weather. The neurons are talking to each other and makes up almost a third of of of of the fight in the in the in the membrane, and then very importantly and something that's becoming I think increasingly important because of the the western Diet she did a lot of early work showing the dots she little Eric Acid, which is An Omega six I said can compete for Dha for uptake pretty much. Any Salva particularly into the developing brain something that I think we probably need to be more aware of, yeah. You mentioned little lake acid, which is a polyunsaturated Omega six acid. That is one of two essential fatty acids for humans. Since the early sixties, the amount of linoleic acid and Americans has increased dramatically is also increasingly women's breast. Milk is that a problem I think it is a problem and potentially large one that the average Americans consumes about six to fourteen percent of their calories from. Lynn. Lake acid and as a result like you said, the linear casted adipose tissue and in the breast milk has quadrupled roughly since the sixties and if you look at the amount that we're eating on average, you compare that to say the mass. Hunter gatherers have a relatively high fat diet. They get maybe up to two percent of their calories. And when we look at the available studies on Lynn, Lake has being essential. Some people say about two percent of calories necessary but it's probably as low as a no point, five percent and the confusing part of this is the phrase essential because it means something very specific nutrition. It means that ECON-, synthesize it yourself and you have to get it from food, but it doesn't necessarily need the mean that you need a significant amount of it for health. So for instance, if you want to study how essential a certain, a mega six fatty so I didn't let. You remove all the other mega six fats from the Diet, and then you add a little bit to see what can reverse symptoms is usually skin symptoms that you see either in rodents or humans the much like the other essential facet, which is Alpha Lynn. Lana cast is a shorter chain, a mega three, these two mainly actors precursors for the more important longer chain fat. So Alpha Becoming EPA DHA or has it becoming rocket on cassette? So I would argue the most of the function of little egg acid in the Diet as an essential component needs to be a precursor for longer chain record on a castle which we can synthesize. So even if linoleic acid is essential biochemical sense, we probably need even less if we can your racket on a cast which you would get if you. Have a small amount of animal foods in the Diet and even then we probably eating several times ten twenty times more than we would be guessing in traditional diets and over time has become a problem again like a sort of loo terrariums because it competes with Dha for uptake in pretty much every tissue the buddy and Dha is pretty much an essential component of O'Brien's and particularly on almost Andrea. Stem talk is an educational service of the Florida Institute for Human and machine cognition a not for profit research lab pioneering groundbreaking technologies aimed at leveraging and extending human cognition perception, look emotion, and resilience. In the lecture you gave that item see you talked about how many people may be suffering from a deluge of processed oils that have become really a staple in the modern diet and I find a lot of confusion on this. In fact, we've received an email questions about this for the ask me anything episode we did maybe I don't know three or four months ago. So when it comes to process oils, what do you see as the primary issue and what's your advice on this matter? Of really understand why people get confused about this and it always seems to come back to ldl cholesterol heart disease. We've been told for decades that replacing saturated fats with plant oils like canola, sunflower, soybean oil reduces ldl cholesterol, and therefore this reduced risk of heart disease. So why is true that these oils can reduce ldl cholesterol if you're play saturated fats with them and there is some epidemiological data suggesting that this is associated with reduced Odyssey's risk. The randomized control trials don't really agree with an either they showed no effects or potential for worse outcomes in those consuming. More of these oil. So the Sydney Diet Heart study is a good example where they replaced animal unsaturated fats with high linoleic acid, content, safflower oil, and Safflower Margerine, and that seems that she increased mortality and increase Odyssey's rights. So in the first instance, I, think there's been a conflation between proximal outcomes and long-term one but I would argue that it's probably mortality and disease risks that people care about more. But in reality, there's so much more to this scenario than just cholesterol and heart disease I do think one of the problems particularly when other people are maybe trying. To refute the claims that these vegetables bad for our health is the very loose terminology being used. So so people will say that plant oils are pro inflammatory been reality. That's not necessarily true. If you feed people soybean oil they, they're not gonNA have this big sort of increase in inflammation that you can measure. There's no like big increase in copd or these other things like you would get if you had an infection however when these fats accumulate and ourselves of a time, they can interfere with normal inflammatory processes because they compete with other fats for normal production of. Normal signaling molecules particularly, those they're anti inflammatory, and again that comes by competing with EPA and Dha the longer chain of a mega three, and again set a couple of times in Nina's O'Brien injury linley acid increases or competes with Dha for uptake into the brain, and then that increases the susceptibility, the brain to injury. So we've done that in in Nina's rat models, you feed them with the Dia-, highland, lake acid, the DHA in the brain decreases, which she also showed in pigs, and then if you into that brain, you get an increased injury similarly if you have A. Highland leg acid again, this in the lab rats and then you make route hypoglycemic or diabetic. The combination of the two is much worse than just either one alone. And this is sort of looking at a damage to the heart. So just in the short term, you probably can't see any negative effects but in the setting of any kind of inflammation injury, then it seems to to really worse than the outcome and I think this is important because the average person is consuming a lot of these and is also on the spectrum towards prediabetes Diabetes Metabolic Syndrome, which is incredibly Common. So I think this is really relevant over the lifetime, but it is really complex topic and some people have tried to boil it down to the mega sixty three ratio but that's also a bit of an over simplification because Salmon Mega sixes are essential health before we talked about that a record on cast it in the brain is incredibly important. So I understand why people are confused but I think that my Advice is fairly simple and it's just you cook your own food the the majority of these in terms of exposures come from restaurant and processed foods. That's where most of these oils go and you heard about during covid nineteen is few people go to restaurants. There's been a crisis in in soybean oil because the restaurants just not using it anymore because people don't use at home. So if you're at home. You can cook things in some olive oil avocado oil coconut oil these going to be better in terms of their content of these of these mega six fats. If you're a scout avoid fried things, particularly deep fried things and I don't think you need to worry about this a huge amount. You know if you have control over the majority of your food and is cooked at home than most of this problem disappears. So Tommy Dakota Heck Snook asset or DHA is a type of a mega three fat and since our bodies can only make a small amount of Dha to consume it directly from food or as a supplement, and there have been studies that have shown women who consumed six hundred, eight, hundred milligrams of Dha daily during pregnancy reduce their risk of early preterm birth. So that raises a question. So what about low Dha? An expectant mother does that raise her risk of having a preterm birth that does seem to be the case A. Particularly in women are high risk free birth, and that's the that's the setting that we see these trials being done. This process is regulated to a degree. So there have been some nice studies again, gather looking at the consumption and content of these fats in the mother, and then then how much gets transported over to the fetus, a rocket on, it seems to be always actively concentrated. So there's the level is always higher in the fetus in the mother bots Dha is more tightly regulated. So if your mother with a lower, Dha. A tribe has no a seafood intake. Then the the percents of works hard to try and increase relative DHA transport in into the fetus. BOTs. A coastal dwelling group and you eat more seafood than than actually you get less relative transport across Oh. So the placetas working really hard to make sure that the right amount of these fascinating getting over to the baby but I think there is a point where his where it's GonNa be it could be too low. There could be some some negative effects and again part of this is I believe is the premature birth is often associated with some kind of inflammatory process. So that could be either in the mother or in the Placenta. And Dha and some of the metabolize it Dha very important for resolving information. So if you're at risk and you don't have enough precursors all because you'll low and they're all being transported over to the fetus so gets enough Dha. Then that may contribute to ongoing found what you processes in the mother, which then precipitates appreciate both. And Reducing preterm birth is critically important because depending on how prematurely a child is born they have about thirty to fifty percent chance of dying or having a severe disability. So what recommendations do you have for expectant mothers in terms of reducing premature birth? In reality, this is quite a tricky question to answer because it's impossible to know whether you're going to have a preterm birth around ninety percent of births in the US Goto full-term, which technically is more than thirty six weeks but this does leave nearly ten percent being born pre Tom and the rate has been increasing recently from Sarah the mid nine percents to I think it was nine point nine, three percent loss chats and the mall. pre-term. You are the greater your risk of later death or disability the current events around twenty two weeks, which which is basically like fifty percent of the way through. But we particularly worry about extremely preterm infants which of those full twenty, eight weeks and they. Will have a fifty percent risk of death dispute as he later in life, there are a number of risk factors that potentially modifiable. So being overweight or obese or underweight smoking alcohol illicit drug use infections like I talked about. So this could be sexually transmitted infections, urinary tract infections and infections. So certainly, there's benefits treating infections when they come up will being up to date on your. Vaccinations if you need to be stress is a big factor which may or may not be modifiable depending on where it comes from. There are some other things that also very important that are going to be non-modifiable. So ethnicity is important, native American and African American women are more likely to have pre Simba's and does this very sort of new and fascinating area of research going into. Why that might be and there are some thoughts behind this continuing EPA genetic signature of the stress that these people have experienced as PA the histories in the US and that is possible changes. The inflammatory states isn't changes the increased risk of Kemba. Then age con change for being under eighteen or over thirty five increases, your risk socioeconomic status and lack of social support also play. A role with road again, be through stress or lack of access to healthcare says, it's really hard to say what somebody should try and change to reduce their risk of of course you know if if you have the ability to change those factors to make sure that your just as healthy as possible before you get pregnant or early in pregnancy than your risk will be much lower. So let's transition talking about preserving brain health at you're talking agency. You got your biggest laughed when you quote something that can once said, which is humans have roughly since the advent of agriculture become dumber weaker and more frail. So why is that well? I think the simple answer is that we've used our big and intelligent brains to engineer rule the difficulty out of our lives. I think it's almost ironic that the processes of evolution and the environmental stresses the official G is she built to expect has created. This fabulous brain is then able to remove those stresses such that it negatively impacts our health and cognition, and that's what I think we're seeing. So, if we are in D. becoming dumber weaker, what do you think we can do about that? So I think this brings us back to the things that you might say physiology expects you know the things that a brain needs to be healthy and a supportive environment is important. So die and sleep but I also think you you need to stop bringing in these stresses that we've been exposed to through our volition and now essentially gone. So frequent moving physical exertion called heat stress and significant. Stimulus. So most adults suggests on autopilot all day work at home, and you know if you think about sort of novel stimulated to the brain and the body, those really seemed to be lacking and that's where I think we can start to talk to intervene and bring those back in. Yes I agree I gave a talk recently, and in the question answer period I suggested that that it would be good to strive to become better animals than to recognize that we are animals and a small percentage of the audience was a gas. Hearing that they had anything whatsoever to do with animals. I think it's right along the lines of what what you've just discussed. Yeah. We just have to accept acknowledge who we are and where we came from it, and then try to build some of that back in. Indeed as you've pointed out in your lectures each of us is issued a single mach one brain the last Last a whole lifetime you know our modern lifestyle probably is in helping us much in this regard. So the question that I think many folks have is, how do we prevent the brain from declining over time prevent th-they declined and also even slow the decline if the declined turns out to be inevitable. I think some decline is always going to be inevitable I don't think we're a stage where we can significantly impact the maximum longevity of human by. Bernie make sure the brain functions as well as possible for the majority of that time, and this is where I bring up that legged stool again and I'm mostly agnostic to how people do it because there are many ways to approach the problem but again, I think in summary. You need the materials, good vascular supply to the brain. So you oversee needs to do all the things to keep. You'll and thalium happy and keep your blood vessels functioning properly, and then you know getting the right supplies nutrients building blocks from the Diet safety against things that can negatively affect brain hill. So sleep is incredibly important. Avoiding certain environments toxins like water quality may play a role at pollution. Sunny seems to be associated with with an increased risk of age related, cognitive decline and. Then, you know like we're talking about stimulus in connection. So regular cognitive workload is important. I, think we lose that particular to the end of our working lives and then into retirement and then social connections. So you know having strong social ties having friendships having those interactions. Humans are those are in credit, and if you maintain all those things and work harder to build them in than I, think is a huge amount of robustness in the system to to maintain function and health of the brain. Dave. asprey will be sad to hear that you think he won't live to one, hundred, sixty I really don't think he'll live to be one, hundred and sixty he might make ninety. Ninety would be just fine for most. Exactly, yeah, and if your brain keeps functioning so ninety I think that's a real good win. You've got that. So the amyloid Beta precursor protein is a membrane protein that normally plays in the central role in neural growth and repair, and later in life however, emily baited can become corrupted and destroy nerve cells, and this is what leads the loss of thought and memory and people with Alzheimer's disease. Can you give us an overview of emily precursor protein and as many functions in the brain? The. AMYLOID PRECURSOR PROTEIN AP is is quite fascinating because we know that it's incredibly important but but people might also say we don't know exactly all the things that it does, but it certainly involved in neuronal plasticity. So like the formation in connection, of Synopsis, between Ron's the transport of certain elements particularly on also the response to neurotrophic hormones and in dementia even though we see aggregates of beats amyloid, which is a cleavage product, a APP, less of the precursor protein seems. To be being produced. So that's that's part of the hull pathological processes that you know less of this is is being produced, but more of is being cleaved accusing potentially. So so having a normal system of production clearance of AP is incredibly important as well. ASSANGE downstream products, but this appears to get disrupted him cognitive decline but also has for some reason become like the one thing that we focus on when I think there's a lot of other stuff that's also gonna be important. Merck Pfizer Lilly and other pharmaceutical companies have spent billions as Carl Sagan says, billions and billions of dollars on drug trials aimed at targeting Beta amyloid. They've all failed essentially Why do you think that is I think that's because most Sims play beats. amyloid isn't a significant causal factor in Alzheimer's disease. Also, what we should more accurately call age related cognitive decline at age related dementia because we'll Alzheimer originally described is probably a case of early onset familial dementia with a mutation of something like the President Jean and beat amyloid is certainly associated in that process but that's not the same as the late onset diminishes that seem to be increasing disproportionately to. Increase in lifespan and which some people have said will cost a trillion dollars by twenty fifty and bankrupt Medicare. So I think we need to think about them separately and thinking about late onset cognitive decline. All Age relates Dementias, which is what most people are going to be concerned about. If you look at both road in human studies, the amounts of Bee's amyloid accumulates in the brain is not associated with either the rate of progression, all the amount of cognitive decline, and then if Utah get removal amyloid to say use a Monaco non-sporty, which many of these companies have tried, it doesn't improve outcome and even if you see less speech amyloid in the brain. Off You've given the drug, it hasn't improved cognitive function. So instead, age related dementia has all the hallmarks in my mind of neuronal metabolic dysfunction and I know that you had Francisco Gonzales a as a as guest previously, and he describes the vascular theory of outside disease where a chronic. Of. Blood flow results in down regulation of metabolic processes because of the lack of supply and then you get reduced production of things like sidestream smoke size complex four in the electron transport chain, and ultimately this results in methodology impoundment and Euronews dysfunction and death. And personally I think my view pretty much overlaps entirely with his. But if I use my three legged stool I, think that any one of those directions can potentially result in this problem and most of this is also supported by work that goes into Dr Gonzales says model. So you can elicit cognitive decline in rodents by juicing chronic reductions in vascular supply or you can do by poisoning the minds. Say with low levels of cyanide all you can do it by removing other rodents from the cage or removing what we call environmental enrichment. If you bring toxins if you remove necessarily materials or if you remove stimulation and connection, all of those can result in cognitive decline. So that's in my mind essentially any of the three legs of the stool that you can remove experimentally all you the each of those also happens in humans but other than some kind of side processes very little of it has to do with beats amyloid. Now, that no you and your wife Elizabeth wrote a recent paper where you argue that Beta amyloid as an epiphenomenon of neuronal stress. Can you talk about that paper and how you arrived? Yet this was a paper. The it was invited to review the general. AP L. Bioengineering, and eventually we sort of collaborated together on and it's cold. A disease directed engineering physiology driven treatment interventions in urological disorders, and if he thought the Tyson was long you should really take a look at the full manuscript because it's pretty epic but but we basically. Through the paper, go over all the main pathological processes associated with both acute and chronic neurological diseases and why we need a better understanding of the broader physiology and environment both inside and outside the body to create better therapies. I. Think. That's where we're missing some of the potential things that we can do and we use beats amyloid in Alzheimer's disease as an example of mistaking correlation causality, which I she happens quite frequently neuroscience and we we just presented the evidence. That I just talked about and what we do know the beats amyloid itself can be damaging. So maybe early onset Alzheimer's or if you have very large quantities and you can construct that genetically in mouse than it does seem to cause a feed with effective girono damage. But in most people, we talk about it being an EPA phenomenon because it's just it's just happening during these other neuronal stresses which are occurring which then a property whatever actually leading to decline. Well, let's now talk about the most common Ronald stressors. You've mentioned a few of them, but this is a good point to review them. These can range from inflammation to sleep deprivation and others. Can you give us a rundown of the list of stressors that you think people should pay attention to? The, the great question and I think that the big ticket items are going to be related to metabolic toxic stresses, injuries, and infections, and with all of these, we see evidence of abnormal protein accumulation in different ratios and different amounts in different places. But you know that includes bees amyloid. So these kinds of stresses you might think of hyperglycemia, insulin, resistance, heavy metals, or other toxins. So Ibm, Aa became this this talks in which you can get from sun algae that that people thought was going to be the root cause of outside disease and it just seems to be one process by which. That, this can happen and we might see something similar in traumatic brain injury or chronic traumatic encephalopathy. Repetitive concussions particularly associated say with with sports or in the military there have also been some studies suggesting that certain infections like herpes simplex viruses or pseudomonas ginger virus associated with amyloid aggregates. Although I will say that Herbie's simplex virus staters recently come under scrutiny, but it sort of just fits into the model. It doesn't have to explain all of of all of the dementia that we were seeing if you kinda fit together. So associated with these things, there is a parallel theory that suggests that amyloid is. Accumulated actively as a response to these insoles because it has oxygen metal collecting or antimicrobial properties, we talked about is very important Farai miles of important because it can try and target this insult, the this come up which which may be infectious or something else. So a such a don't think this huge about evidence to support this theory about it would make sense of this, some kind of response to a noxious stimulus and all of these things seem to result in some accumulation of amyloid visas. So anything's possibility and as you try and let bill this big picture of causes of of age related. Dimensions I think it seems very likely that this broad range of things can cause issues and the amyloid visas essentially just being produced kind of side product and they may get to a point where you have so much that it becomes problematic on its own, but it certainly doesn't seem to be important if you're trying to to intervene or prevent these things happening early on in the process, this is probably a good time to talk about the microbial which are known as immune system of the brain. Can you give us a little rundown on their importance and explaining exactly what they do in their general sense? Thing. Is Worth me starting by saying I'm far from an expert on market glare because there since you their own complete weld of complexity and research that just gets deeper and more complex almost by the day. So as a neuroscientists, my training is led me to be a neuron centric. So so I may just rely on the mike clear dummies definition, but they're essentially the the resident immune cells of the brain like you said, and they come from a similar lineage to macrophages elsewhere in the body that people may have had of the very important in the response to infection or other injury, but they also have sort of A. Static prices like they're involved in in pruning sign ups is in your strengthening and weakening your connections as we as we learn new things will change you know other external factors and Michael Lia are increasingly being targeted often neurological injury because they can have both pro inflammatory and anti inflammatory phenotype. Soon, there the several that fit into those categories, but seems to be some evidence that. Pro Inflammatory Michael. Not Adequately switched off or you know switched phenotype back to a more resting or anti inflammatory phenotype. They can then contribute to ongoing injury. So that's why Michael here becoming sort of a big arena and Europe protection field as as people try to figure out how involved and then maybe whether we can talk therapy. So, Tommy I'd like to back up a little bit and talk about how inflammation is associated with almost all neurological disorders. Can you talk about that and also the role of fatty acids and inflammatory signaling in the brain? So pretty much every chronic disease. You know not just those in the brain that seems to be this element of chronic inflammation and when you're thinking about how these prices thought, and then how their resolved this is where facets become very important and you know a normal inflammatory process you know in response to something is should absolutely happen. We often think about inflammation being a bad thing. But in reality, it's not you just need to be able to switch it off when the you've done the healing switching off his part of the healing process and if you think about. Signals in the immune system as of this sort of inflammatory signaling to be very broad group save your cytokines. which are proteins, and then you have your lipid mediators, things like Prostaglandins, leukotrienes, and these The latter are produced from the mega six, three fatty acids that we were talking about earlier. So the initial immune response is logically coordinated by some prosecutions leukotrienes created from rocket on a cast, long chain mega six, and that's part of coordinating the response but eventually, you need to switch over to a class which we might call it Michael also somehow dampen down the inflammation as we resolve it, and this requires lipid mediators from the mega three fatty acids, EPA Dha. And a lot of this has gotten attention recently from the work of Charles Sahan and specialized pro resolving mediators. SPM's they call them in I. Know You had David May on the poku previously talking about this and when your in the process of trying to resolve this inflammation. Then again, EPA DHA becoming poor precursors full these resolve INS or protections marines, which which were involved in in kind of you know the the the final resolution and healing process going back briefly to. Little acid. What's interesting is that it competes with the same enzymes that used to create these mediators and instead create something called oxidized Linda Lancaster metabolite. So Oxfam's and these seem to be increased in a certain disorders such as Alzheimer's disease and they as well as competing for the those the same enzymes they can stimulate this initiation of chronic inflammation rather than letting the body heal and resolve the information by using some of those are the mediators, defoe a threes. So timing I suspect some listeners are wondering what's the difference between acute inflammation, chronic inflammation and chronic inflammation determine that's thrown around a lot these days. So can you explain the difference between the two? Yeah absolutely it it can be difficult to kind of conceptualize chronic inflammation because it's not necessarily something that you can actively see when people think about acute inflammation you're thinking about the cardinal signs of inflammation which learned in medical school, which ruble Callo Dodo and Chuma, which is flattened for redness swelling pain and heat. So those are the things you might see. If you sprain your ankle, all breaking arm or something that's the acute inflammatory process, chronic inflammation. It's usually happening like deepen a tissue somewhere and can go on for months and years, and you might be able to measure something in the blood like you know, maybe people have heard of a p level or something of that, and that sort of a lowest level might indicate some kind of chronic ongoing flosse process. But in reality, it seems to be driven at the tissue level like the immune system in that tissue, not resolving and continuously sort of propagating. It is that's going on, but sometimes it's very hard to spot, and then that's just because it's the sort of this very low sort of indolent issue in the brain is almost impossible to easily measure a. then you'll see the same thing in the fat tissue if you're a beast or in in other tissues in sort of heart disease and types of diabetes. So these things a very, very common, but it's not this very obvious thing competitive what you might see an Aq-. Information. One you lab has been looking into is how modulating micro glee can reduce oxidative stress. Can you tell us about that research and I just have to say my probably my favorite cells so I'm looking forward to this answer. Well. So so again, I'll I'll repeat I'm not an expert and probably leave that to to people like you and Elizabeth and. I essentially kind of fell into this area and largely because of collaboration with Elizabeth and some other colleagues including one who has significant. Expertise Gwen Garden who you know that UNC Chapel Hill Dawn. And in some of the work that we've been doing, we've been looking mainly at the drug as my sin in the. Antibiotic. Career people have heard of his e pack and it's very interesting because it causes a fingertip switch likely it seems to turn them for these pro inflammatory Markley back to these more anti inflammatory market here, and in the lab we have again in collaboration with with Elizabeth, we have developed a slice culture model. So we take brain slices from from the Ferret and those include all the different structures of the brain and we. Can then do a model of stroke in in cell culture, but allows us to much more easily look at things like career, and so if you do this injury model, Goule Oxygen Glucose deprivation, which is essentially like removing the materials that that that you need for health and this is something similar to a stroke. In this kind of cell culture medium you see increased injury like like he would if if you had a stroke or. something similar like the Nina branches you talk about. The Michael Potter is they become activated and if you put. It into the medium you then see less mockery lactation and reduced oxidative stress, and similarly, you can give to mice into neonatal rats off to a neonatal stroke type injury, and they seem to have a reduced by of injury and both like the brain we have they have less loss of of brain tissue and they have improved neuro behavioral outcomes they a functionally much more intact than they would be if they weren't treated with it, and so we're now trying to translate as. To Law models, particularly the Ferret. So again, looking at both priests brain injury and term brain injury where both of these things will be relevant and. Is. Probably one of the more promising therapies that we might use India NATO brain injury We think a lot of it happens through its actions on my clear but we also know that it's it's safe in pregnancy and Indiana already FDA approved. So that kind of makes it closer to being a translated to humans. The problem however is the micro Leah Have Long Memories. So that raises the question of how you reduce micro Galil activation. This is a fascinating area I and I think that some of it might underpin those things that we talked about earlier in terms of infants being born prematurely or exposed inflammation in the womb, and maybe some EPA genetic effects that are happening and a low of that might be creating memory, and my quickly then results in them being either more sensible won't more pro inflammatory throughout the rest of life something similar might be happening in macrophages elsewhere in the body, and for instance, if you look at Ala Premature Brain Mullin. The. Ferret. And then take those brains several weeks later. So the equivalent of say a child of a few years old then then you take the mic clear out of those brains and you look at what genes expressing, they look very different from control clear. So they're expressing more genes associated with inflammation and fewer genes associated with more of an anti inflammatory phenotype. So there's a lot that we can dig into that but the those market definitely look different and again, this is several weeks and years developmentally further down the line. There was a fascinating study looking at. Margaret. Activated in the brains of people, months or years after its romantic brain injury, they used a single photon emission computed tomography or scan and a tricycle. Nine five, which basically has a high affinity for activated or pro inflammatory multiplayer, and in those patients, they saw increased Leo activation in the Alamo, which is basically the relay station for sensory and motor information to the CORTEX and this activation persisted for up to sixteen years after the injury and the degree of activation was associated with cognitive processing speed in those people. So this suggests the even several years after injury he still have this ongoing chronic inflammation in certain areas of the brain, and that is actively affecting cognition, and so this this is again, polly makes a very interesting potential target as for what we can do about that. Like I said, this is probably a question for. Elizabethan and dawn as we develop better techniques to deliver therapies to the brain. But I do think that reducing the number of other detrimental things we expose our brains to will be beneficial. So making sure we have the raw materials to create a pro inflammatory response we talked about the fatty acids maintaining insulin sensitivity, super important I think those things will help. But we certainly also have a lot more to learn. To Tommy just searching the subject a little bit but still thinking about oxidative stress and McClellan. We, recently interviewed Francisco Gonzalez Liam. As you mentioned earlier about his research methylene blue as a narrow protecting this episode. One is seven on stem talk and since that interview you and I have been discussing the possibility of looking at methylene blue to protect against hypoxia induced cognitive decline and individuals working altitude is a big area of research here at agency and I know that we're both excited about this upcoming study. So what are your thoughts? Not? We've been digging into this a little bit on the potential. Meddling blue in the setting of acute brain stress or injury, not just hypoxia but just in general yeah I think that methylene blue is is an incredibly interesting potential intervention and both acutely and people want to try and maintain cognitive function in high poxy but also maybe after keep brain injuries as well and there are some people who Stein set to look at that same method blue is a synthetic dye. But at low doses, it's essentially an auto accident so it can provide a free supply of electrons. into the country activity accumulates in areas of the brain the mathematically. So essentially going to go to where you want it to go and. It's GonNa continue to provide electrons even in the face of maybe some kind of decrease in material. So so if you think about oxygen during hypoc Zia blood flow to the brain tends to increase but glucose uptake in the use of oxygen. Relatively, I'm can decrease in this can be mitigated by giving small doses of methylene blue and and most of that's been done in rodent studies. But A, you can basically increase the efficiency of extraction of Auction and you can increase glucose uptake. You can maintain metabolic rate under hypoxia if you have methylene blue onboard and then if you if you look a acute human studies, you give methylene blue and look at the functional MRI is. An hour or so later you see increased connectivity in in the active areas of the brain and improved short term memory performance, and the the idea would then be the in those people who are going to be exposed to high pokes here you can give methylene blue and that's going to help them maintain function activity in a crucial areas of the brain that they need for decision making or whatever it is that going to do. So I think it's you know there's there's a lot of potential there, and if you get the dose and timing right I think is an exciting way to potentially ensure people maintain cognitive function with they're when they're under stresses like I. I. Agree I have to say as you're talking Ken, stuck his tongue out, which is coated in blue. He's actively testing. So I'm often and. That is true. And so many ways. So it's increasingly widely appreciated that maintaining insulin sensitivity is critically important as we go through life but here in the united. States and really and. It's it's not just that I'd states if you WanNa see a good example of this visit the Middle East like the UAE, for example, in most of the world rarely we're not doing a good job of maintaining insulin sensitivity. I've seen it reported that about eighty percent of Americans have some kind of metabolic disease. Can you help our listeners stand why this is such a major health issue and why we should be concerned about it. It's. A major health issue because those processes are associated with pretty much every chronic western disease that they might be the listeners might be trying to prevent or stave offer as long as possible including cognitive decline and the the numbers that you quote come I believe come from a fairly recent paper by Araujo Atoll cooled prevalence of Ottawa metabolic health in American adults, and they looked at seven years of Hans as about nine thousand people and using some of the premises of Metabolic Syndrome. So waist circumference, blood pressure, blood, glucose, triglycerides, Inacio cholesterol they tried to see who had optimal levels of those things and they estimated that eighty seven point eight percent did not or had sub optimal metabolic health. And she argue that it's it's going to be less than that. Always going to be more than that with more health because they're cuss also blood glucose and Chagas rights were one hundred and one hundred and fifty milligrams per decilitre respectively, which if you're looking at sort of later health outcomes, you probably say optimal is closer to less than ninety glucose in less than a hundred photographer is. So what you're left with is that basically a very tiny proportion of American adults are in good metabolic health, I mean no. From elsewhere, that's more than forty percent of US adults have at least one chronic health condition and more than fifty percent have some kind of long-term prescription medication assume reality the average American again, don't want to just bag on. America. It's definitely in seed in multiple other countries lived. These sort of West is lifestyles on average where we're sick and that includes some communist bollock disease or instances, and what comes with that will things like heart disease and dementia, which which people are trying to to avoid. Yeah I always hate that term Westernized. It's sort of a like healthy whole grains. It's It's like built into the discussion but his vacuous. So if you go to India, for example, you really not westernized but they have these problems in spades or Italy, which is the cradle of Western civilization they're doing much better I they're eating the Mediterranean. kind of this is the whole other point. Back. You was term. Up Equally, you're also the I guess the reason why? It's so easy uses because as soon as I say westernized and you know then you know what I mean even if it the the west, an aspect You mean back. Modern. Modern. skin-tight. Stem. Stepped up. So I have to say I see what Tommy's white Elizabeth means when she says the Tommy's always researching the scope of his interest and expertise. It's just absolutely amazing. How many people do we know that work with newborns with neonatal brain injuries as well as Formula One race car drivers that's pretty widespread, avid St Thomas the only person that I know just one of those who'd be enough to be the only person you know. Yes Yes, Don the range of Tommy's research is indeed impressive and I was particularly interested in what he had to say about the physiological and metabolic responses to brain injury in their long term effects on brain health. If you haven't listened to our two part interview with Dr Franciscans Ali's Lima which also dealt with brain energy and brain health in particularly brain energy metabolism. I. Think you'd find it very interesting. Highly recommend looking up episodes one. Oh, five and one. Oh, six listening to Francisco in Tommy back to back. We'll give you a great perspective on. Three or four fascinating aspects of brain health definitely agree can, and if you enjoy this interview as much as I did we invite you to visit the some talk web page where you can find the show notes for this and other episodes at stem talk dot us. This is renee signing off for now and this is Ken, Ford, saying goodbye until we meet 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 items to rate the podcast and perhaps even writer 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 the guests we interview.

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