PNC, Conrad Howitt, Nicotinamide discussed on The Peter Attia Drive


He put nicotinamide on yeast, and we could measure the so to activity by the color, and if sorta was marked if they ten read and he walked into my office, one of his first experiments. We worked on to. And and he said they'd somethings. We had we didn't get activation. We got into Bishen. So the yeast gone Rydin. I said Kevin doesn't matter. What happens is expected that even better that led to a paper that said that vitamin B three high doses. Inhibitory of tunes now the labs around the world use nicotinamide as an inhibitor for certain I wouldn't recommend taking really high doses of nicotinamide. Why is that few answers by chemical answer is that a an volt pocket in this or two and structure that measures nicotinamide levels. And it's a feedback. Loops nicotinamide is to get nerdy is the product of the reaction. It takes a D cleaves it. Oh, I got. So just the negative feedback. Nave seeing too much be three and saying I have too much of my output slowdown on a doubt. Exactly. So we struggled with that. We couldn't get any going to sell to big in with mammalian cells difficult us, we were looking at ways to make more energy in the cell. That was our original. Thesis before is virtual was on the radar, and we would turning on and discovering the genes that made in dean yeast, and we clone some of the genes in that way. And there was one particular one that was called peon is called PNC one, and it had been studying the context of tobacco Lhasa's, and what we found was that when we Clark restricted e cells, this was one of the most highly up regulated genes in yeast cell, which was very unusual people had discovered this before in their own lab. But they will wondering what the heck is this a AD, synthesis? Parkway got to do with calorie stricture and got to do with stress, but we knew exactly what was happening. This is a stress response that was turning on eighty production and activating so tunes. So we had a offense nature paper actually on that two thousand two I think doesn't three and we found the PNC one could mimic collection and raise AD availability. And if we knocked out the PNC one, gene e so. Didn't live longer than calorie restricted them. And what's really interesting about that? I think is that PNC one doesn't just get turned on by Clark stricken, it's turned on by heat, low amino acids, salt high salt, and so this is a gene that senses the environment and turned on the to exactly what I was explaining earlier about those early lifeforms on the planet sent their environment. And through an in other ways, they can turn on these parkways defense. So where did you go from PNC one to receive neutral? Well, we we teamed up with company at the time they'll called by them all and they will making reagents for H essays, this kind of thing and Conrad Howitt's was a scientist there, and he had invented wasn't even available yet an essay force or to an activity in vitro. I forget why he reached out to me. But he said, hey, maybe I wrote to him. But what happened? He sent me some kits to test and they worked and it looked great. What was the gold? Pandered prior to these kids. Oh, gosh amid mix to an activity required western blotting, which is detecting Gilberto. It was horribly hard still is and this is a very quick way to look for molecules what Conrad did was to take that essay and looked through his collection of molecules BiMAL. They had libraries of these things and to the first molecules that were that were discovered by him to change activities sort one humans at one were couple of plant molecules now he found plenty of inhibitors. That was that was inhibiting wasn't the hard part. Exactly. But he called me up. And he said David this is a something's weird. We've got these molecules that seem to activate enzyme, and that that's great. That's what we need and goes, well, I don't know if it's real what you know..

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