[00:00:00] Host Create clip what gets really interesting, and this is something most scientists don't even know about yet. His Level three The deep layer of aging There's actually a DNA clock that tells our bodies how old we are. I could take your blood and read it, and I could tell you roughly when

[00:00:17] Host Create clip you're gonna die. Everyone hope you enjoyed this episode brought to you by our sponsors at Peak T. Everyone welcome to hell theory. Today's guest is David Sinclair. He's an acclaimed Harvard professor who's doing some of the world's most ground breaking work on human longevity. He was named by Time magazine as one of the most influential people on the planet and his new book, Lifespan. The Revolutionary Science of Why We Age and Why We Don't Have To is set to permanently shift how we think about the inevitability of aging and possibly even death. That is exactly where I want to start. So this is my favorite topic. I want to live forever. I make no bones about it. I know that right now, though, I'm on a collision course with death. So you have a really interesting theory about what makes this age that if I'm not mistaken. You call the information theory of aging. So what exactly is the information theory of aging, and how do we take advantage of it?

[00:01:18] Host Create clip So aging actually has been worked on for about 5000 years or more. And just in the last 20 years we've come up with a set of hallmarks of aging. There about eight of them. And I think many of your viewers will know that there's telomere attrition. The ends of chromosomes get shorter. Mighty Condrey, the power packs. We're running out of energy as we get older. There's a list, a long laundry list. And most of the people in my field have said, OK, we've we've figured out aging. We've got this list we put in a nice part pie chart and that's it. But what I'm saying is that why does all that stuff happen? It's not enough just to take off what happens. You have to understand. Is there a upstream cause of all of that? And so in my book and in scientific papers, we are now putting out for the scientific community to read as well. What we think is going on is that our bodies are losing essential information as we get older. That drives many, if not all, of those hallmarks that we know exist.

[00:02:15] Host Create clip So what, in what way is the epi genome involved in this? How are we losing the information? Give people a quick little diatribe about the difference between genetics, which I think they get, and then the epi genome and epi genetics and how that plays out? Yeah,

[00:02:30] Host Create clip yeah, for sure. It's not that complicated. There's really just two main types of information in our body that we get from our parents. The first is genetic. We'll know about DNA in the four letters a. T. C. G. It's a long molecule and sell, and it's a string of letters that's digital. That's like the music that's on on a DVD, those things we used to use to store movies. But there's another level of information that above that in cells, which is the reader of the information that's called the Epi genomes. And that really is different because it's analog information in the same way that records and cassette tapes they sucked. They were terrible at storing information, but the problem is we have an analog version of information the Epi genome, which controls which genes in the string of DNA are turned on and off. But

[00:03:20] Host Create clip why are you considering that analog? I don't think I understand how it actually works. Like I can imagine DNA sequences as just sort of repeating the A T c G code. But what is analog about the EPA? Gina. This reading about in your book is the first time that I began to imagine in a different way.

[00:03:41] Host Create clip Well, it's very clear that if you just have four letters that's digital, so we understand that. But the EPA genome is the structure of how the DNA is organized. So Dina isn't just flailing around like a string. It's actually packaged up around proteins We call his stones, and it's like if you spill your hose in the garden, you loop it around and then you can put those loops into bigger structures. Then you get a chromosome, which you can see any high school student could see under a microscope. That's that Crow Metin structure, as we call it, is the EPA genome. And so when when the hoses loop tightly and spooled up, that's stopping genes from being read so genes are off when they're compacted, but also if the cell needs to read certain genes and no cell needs to read the nerve cell genes and the liver cell needs to read specifically the liver cell genes. And so they opened those ones up, and now the Selkin to get access and read those that's an analog system because it it's varying all the time. It changes when you wake up what you eat. So

[00:04:36] Host Create clip it is literally the amount that the DNA is unspooled and the place in which it is unspooled so that it can be read

[00:04:46] Host Create clip right. And that's what determines the cells, function and identity, which we know when we're born. We're 26 billion cells. Each one of those cells knows what it is and what it has to be. 80 years later, it and its descendants and over time, what I'm saying his aging has caused because cells lose their packaging and then eventually cells lose their identity. Disease answered ensues, cells check out, they become zombie like on denounced, in essence, rests in essence, and then our organs fail and we die. But until recently, we had no idea why that was happening.

[00:05:19] Host Create clip And so why is it happening?

[00:05:22] Host Create clip Well, so the packaging is the really important part because much like the software runs the code, the EPA genome controls which genes are on and off. And if you stress the system, and by that I mean biological stress. And the biggest stress you can cause to a cell is to break its chromosome because it's gonna die if that if it doesn't fix it or worse for the body, you get a tumor. So the cell has to hunker down, stop dividing, arrest just about everything is doing and then try to repair the broken Dina. But in doing so, it has to do two things. First of all, it has to take proteins from somewhere else that doing good job keeping the cell from functioning, making sure the cells functioning correctly. Those proteins are used by the cell to repair the DNA that's broken. But also what's happening at the break is that that's all opening up a cz well, because you remember if you if you break a DNA and it spooled up, you can't fix it. You can't glue it back together unless you unpack it.

[00:06:15] Host Create clip Stick it back together, and then you gotta repack it. So this movement of proteins and the unpacking repacking of the DNA, I believe, leads to cells losing that original youthful what we call a gene expression pattern of how the genes are turned on enough and nerve cells. As they get older, they lose their ability to stay. Nerve cells and liver cells lose their identity as liver cells.

[00:06:38] Host Create clip All right, so I do proteins the way that you're talking about them sound like little creatures. I think of them because of my background, like powder like just sort of inert molecules, which clearly judging by the way you're talking about them, they're not. I've seen them animated before as having, like, articulate herbal shapes and they actually move. Is that accurate?

[00:06:59] Host Create clip That's essentially it. It's It's super exciting when you realize that proteins aren't just blobs or powders in the cell there. Actually, little little machines like Pac Man that go around and they can change the function of other things that can package the DNA, and what they do is they create chemical reactions that normally would take a 1,000,000,000 years to happen. This is what an enzyme does. That accelerates reactions. And so we've got about 20,000 different types of enzymes in the body on they do different things. But what we've discovered over the last 20 years, it's There are certain types of enzymes that help package the DNA and help with the dean a repair these with ones that doing the Ping Pong game, and without those we're screwed. We basically will will age more rapidly. Conversely, what's really exciting is we discovered that you can make them more active to make sure that DNA is packaged correctly and the repair is very efficient. And there are ways you can do that. Exercise dieting, being hungry. They allow these enzymes that control our body and make us healthier. They make those enzymes much more active. So instead of a Pac man doing this, you exercise you diet, take him, take a molecule that we work on, and we'll go around and fix everything much more efficiently and keep your younger for longer. We think,

[00:08:15] Host Create clip Why do you use the Pacman analogy, which makes me think it's eating something? Is that what's happening? Is it eating cells that have a level of sin, essence or Is it more Bob the Builder? And it's going around tearing Something's apart, putting some things back together. Yeah,

[00:08:29] Host Create clip it's it's more like Bob the Builder, but I think a good example for at least the enzymes that we work on. Cold, sir, to ones that protect the body. They're like a little tiny pair of scissors. They chip up clip off chemicals called Siegel's, and in doing so when they clip off Theus eagles off those packaging proteins, the Deena gets more compact, and that's called gene silencing. And over time, as we get older and through this dean, a damage process, the sort to ones get inactive. That distracted by DNA repair and the packaging of that DNA that hose spooling starts to loosen on. Now, genes that have no business being on in the brain come on. And partly I believe that's why we have these diseases of the brain.

[00:09:14] Host Create clip That's so interesting. Um, okay, so one I want to know from a lifestyle perspective, what are we doing that speeding that up and then to what can we do from a lifestyle perspective to begin slowing that down and reversing it?

[00:09:30] Host Create clip Well, so I've been studying thes enzymes. The sir to INS we have seven in our bodies have been studying them for about 25 years, and what we've learned is that they respond to the sailor environment. There's a chemical that they require for gas. Think of them as the fuel called n a D. And there's another molecule that is like the accelerator on the enzymes. Ah, that makes him going even faster. And that's one of them's called resveratrol, which we discovered years ago from red wine. And together they actually do really great things on these enzymes and make them keep the body younger. At least for 25 years we've been studying mostly animals and even little fungi yeast cells. And what we've learned from those studies is that these are largely involved in responding to when organisms are under threat of survival. So how do you make the body feel like it's under threat? Adversity eso won is run a lot, or at least become out of breath. You know, a few times a week your body will say, Old man we had were to outpace one of those sabre tooth cats again. Gotta go to build up a body on the other is to be hungry either a couple of times a week or every day. You know, skip a meal or two, and then your body will turn on these certain ones make more of that fuel in a D for the enzymes. And we think that's what's in part responsible for the health benefits of those lifestyle choices.

[00:10:52] Host Create clip All right, One thing, though, that you talk about that I found really interesting is this notion of what may be good for you when you're young. May come back to bite you in the ass when you're older. So it's like the whole notion of for me sees that a little bit of bad is actually extraordinarily good, which is exactly what you're describing. Now get out of breath through all this stuff. And so when the information started pouring out that the only thing across every known living organism that extends life span is to eat less What you talk about your own book, it feels like you're saying to do it. For that reason, just don't put as much stress on the system. But now I hear you saying, you know what you actually want to do is stress. The system won't that stress. I just ran from a lion. A fucking starving. Won't that begin to stack up and become problematic? Well, actually, if

[00:11:39] Host Create clip you step on a snail, it's gonna die. So there's there's certain amounts of stress that you don't want to do. But what you want to do is get the body to fear adversity and the future, but not enough to cause lasting damage or the unspooling of the DNA that will lead to disease and eventually death. So you don't want to overdo it. You want to be a little bit puffed. I want to be a little bit hungry. But of course, starvation malnutrition is not gonna make you live longer. So it's a fine line. And what we've learned from many animal studies and increasing numbers of clinical trials in humans is that you want a pulse. It let the body recover, not constant. We usedto make animals go hungry all their lives, and it worked. But it actually works better if you let them recover, and I think that's that's the secret.

[00:12:20] Host Create clip Then let's really dive into that. So I'm guessing you're talking about where animals were denied. Something like 20 to 30% of their caloric intake for very long periods of time is extending their life by what, like 30%? Um, so super interesting. But you're saying that if their caloric intake over a long period of time is roughly the same oven animal that's just allowed to eat until it's satiated, that if it's done in a pulse pattern of hunger and almost over feed, they actually have the same benefits as the animal that has a chronic deficit calories. All right,

[00:12:54] Host Create clip well, let's be clear. Nobody knows what the perfect diet is. So even when it comes to fasting, it's all largely based on rodent studies. So what I can tell you about the rodent studies, which I'm very familiar with, is that if you take a rodent and reduce its calories by 25% for its whole life, it will live longer 30%. But it'll be really miserable and aggressive, and that's true for us as well. I've tried calorie restriction for about a week, and I gave up. I was pretty angry, but what we discovered, my colleagues discovered, is that if you it's not just what you wait. It's when you eat. That's important. And what's being found is that if long as you have that period of hunger, um, in a mouse city can feed them every other day, then they can gorge themselves much as they want. And they do. They eat about 90% of what a mouse having free access to food would eat. Um, but they they have the same longevity benefit as a mouse that's always been hungry. And if that's true, what that means is for us is that we can enjoy life as long as we have that period of hunger once a day or maybe twice a week, and I believe the only reason we age.

[00:14:03] Host Create clip Um, you know, we could live for 1000 years. Otherwise, the only reason we age is that our repair systems become complacent. You mentioned that What? What is beneficial for you when you're young? Come back to bite you when you're old. What we think is that these repair systems are very good when we're young, so the idea is it's called antagonistic Play a trophy, and I think it's right, and that is that we evolved to stay healthy and alive and fit toe where 40 and then the forces of natural selection declined after that. Because we've essentially bread, we've often had Children, but we don't need to stick around beyond that. And building a body that will last 1000 years is pointless at that, you know, so most species only live as long as they need to to reproduce and then a little bit more. If you're a mouse that could die within two years, then he build a body that last two years. If you're a whale that has no predators, you can live for a couple of 100 years. That makes more sense.

[00:14:59] Host Create clip Why?

[00:15:00] Host Create clip Why does the Whale live for a couple 100 years? Like I would say, it's pretty safe to say. Certainly at some point our past we became a pretty clear apex predator. It's not that things couldn't take us out, but I mean by and large, obviously looking at how far we've come, they didn't so why would we only live to 40? Is that whales continue to breed and be useful in that sense?

[00:15:22] Host Create clip So that's really super interesting, and very few people talk about this. The reason is that we were not at the apex of the food chain until recently, but in a world where we typically would die from starvation or from war. A lot of men didn't make it to 40. Because of that, we were at the middle of the food chain. Only now we we actually we barely have a chance of dying before 70 or 80. Unless we're unlucky, give us another five million years of evolution. We could evolve 200 year less spends. That's what should happen if evolution continues. A whale has bean at the apex for about 30 million years and David being allowed to evolve those long life spans. We are just like them. We share most of their genes, their warm blooded. They produce milk, they're conscious. They basically us in the sea. So anyone who says we've reached our maximum limit doesn't know what they're talking about.

[00:16:16] Host Create clip Talk to me about this notion of resetting the biological clock. How do we do that? What's the mechanism? And so obviously going hungry? Occasionally exercise is gonna help. But I know that you have a regiment that I'll lovingly call a regiment of drugs were precursors. The things that we can take. What can we do to reset that biological

[00:16:37] Host Create clip clock? Well, there are different levels to resetting aging. There are three levels that we know of. The first is pretty easy to reset or t manipulate. These air the proteins that turn genes on and off very quickly. We call them transcription factors, and they they basically read a gene and make a protein. That's what they do. That's level one that's easy. Go a little bit hungry. That'll change. Level two is a little bit harder. The level two is not just changing which genes are quickly turned on enough, but actually silencing genes for a long time. And this is where my enzymes that we work on this, or to one's coming to play. Let's go back to the Pac Man. They clip off a Siegel's off these packing proteins. You spool up the hose, and it became becomes locked in that that gene gets silenced for a long time. So to do that you can exercise. You can diet, but you also I think you need a little bit of help is, well, what gets really interesting. And this is something most scientists don't even know about yet. His level three. The deep layer of aging.

[00:17:41] Host Create clip There's actually a DNA clock that tells our bodies how old we are. I could take your blood and read it, and I could tell you roughly when you're going to

[00:17:50] Host Create clip die. What we could do that. What are you looking for? We're looking for

[00:17:54] Host Create clip chemical groups that get added and subtracted to our DNA. The long string. So you get chemical modifications in predictable ways as you get older, starting from conception. So even in the womb, even as a kid, even as a teenager, your aging based on this clock that goes up linearly and where you fit on that line, it's very accurate. That tells you your biological age.

[00:18:16] Host Create clip But how do you know when the person's gonna die? Is that just basically go straight lines? Is the actuarial tables over the human average human life span is 86 is that we mean or is there could you see something specific in my line that would say, Fool, you're headed for 68. Sorry. No, it's

[00:18:35] Host Create clip not. Not specific, but what it based on is machine learning based on thousands of people's code of mutilation on the genome and comparing that to their health and their date of death.

[00:18:46] Host Create clip Fuck, that's so interesting. So if you were to take my blood right now, what would you look for exactly?

[00:18:51] Host Create clip We would read the meth elation that Kemp these chemicals hydrogen oxygen bound to the DNA chemically physically bound. And those accumulate as you get older in very predictable ways. In fact, they're so predictable that we can use the same clock to measure the A dog's age and humans age.

[00:19:09] Host Create clip Whoa! All based on methylation, right? Okay. What causes methylation?

[00:19:15] Host Create clip Well, there are two classes of enzymes. The ones that add the metal chemicals and those that subtract it.

[00:19:20] Host Create clip Okay, how do I take a boat load of ones that subtracted? Ah, that's what we're working

[00:19:25] Host Create clip on Now he's the key Level two aging reset, which we can do by some of the things that I'm doing in my life. Probably you are, too, those on permanent changes. You can't just do that and expect that Take take one treatment and you go on living for another 10 years. Okay, because level two isn't as permanent. It's somewhat permanent than level one but level three is truly permanent. It you could reset yourself 10 years and then go back and then wait another 10 years and potentially reset the clock again if you know how to do that. And we're just starting to figure out how to do that.

[00:20:02] Host Create clip Okay, so level one diet exercise. Cool. Got it. Level two, uh, met Foreman. You taking that foreman? Right? Okay, so I've talked about this on the show before, but explain what is meant, Foreman. Why's it prescribed diabetics? And now, why is a seemingly rash of non diabetic people taking it?

[00:20:21] Host Create clip Yeah. So there are three main pathways that regulate aging and animals, and probably in ourselves. There were the sir to ones that I've talked about a lot today there's one called m tour which responds to how much amino acids are. How many amino acids in your body? It will hunker down and protect the body. The fewer amino acids it has access to. Okay. Okay, then the third is called a M. P. K. And this is the energy sensor. When your body has low levels of energy, it will allow the body to hunker down and protect itself. from diseases. But why am P? K is worth mentioning is this is one of the targets, as we call it off the drug metformin met Foreman will activate this M P K pathway and make the body think that it's hungry when often it's not. And also keep your blood sugar levels Maur steady.

[00:21:12] Host Create clip Why would I hungry at a cellular level? Or I actually experienced hunger

[00:21:17] Host Create clip at a circle level. Okay, But it also has an interesting side. Effect is for a lot of people, myself included. It's a bit harsh on the stomach, so it also reduces my appetite. But what's great about Met Foreman is that it's being in millions of people for a few decades, so we know the side effects the role. Caitlin

[00:21:34] Host Create clip Sorry, really fast. So Met Foreman is creating at a cellular level the sense that I'm hungry and you're saying that from a warm eases perspective of a little bit of bad, it's like stressing this system, and that's why we think it works.

[00:21:47] Host Create clip It is it's exactly doing that, and so that it actually helps the body respond in a way to boost the energy supply. So one thing it does. That's that's undeniable. Is it? Boost the level, the numbers of mitochondria. It

[00:22:00] Host Create clip actually creates additional mitochondria, so your cells are getting more efficient or more able to generate energy

[00:22:07] Host Create clip right over the long run. But in the short run, what it does is it actually poisons part of mitochondria. So it's It's a little bit of poison that leads to benefits down the line. What part is poisoned? It's called complex one so that there are protons that are in one part of the area, the mitochondria in a membrane region and the cell builds up. Protons becomes really acidic in that region, but they sell wants to release them. So what they do is they put little pores in between the membranes so they can leak from the high concentrated zone to the low concentration in the middle. And as they passed through that poor, it spins the poor around, and that's spinning physical. Spinning off that protein will generate chemical energy called a teepee.

[00:22:56] Host Create clip That's how 80 piece created without a

[00:22:58] Host Create clip teepee with dead in about 10 seconds.

[00:23:00] Host Create clip Yeah, Okay, that's crazy. Interesting. Uh, and you're saying sorry to go back to the poison. The poison is elevating those levels, which is causing Maur to go actually

[00:23:10] Host Create clip decreasing 80 peach in the short run. So the cell says, Man, I haven't got enough chemical energy in a teepee,

[00:23:16] Host Create clip so that's what forces it to create. More mitochondria, right? So that's the poisoning part. It is. So the increased number of mitochondria is in response to these light poisoning.

[00:23:26] Host Create clip Exactly. But they're two other important points, the cells in our body. Also, I think that they need to become more sensitive to insulin, which keeps out glucose and sugar levels more steady. Okay, Yeah, that's key, because that's what helps the diabetes type two diabetics recover and, you know, prevents the disease from getting worse. Yes, the second is that it's just being discovered in humans that if you take Met Foreman a lot of it and exercise, it can blunt the effects of exercise on building mitochondria. What we think is going on is that you don't want to always have metformin in your system, or your body won't have a chance to recover from that slight poison. I'm not gonna prescribe anything. I'm not a doctor, but we think it's best better to take met foreman on days that you're not exercising and recovering and posted against you got Matt Foreman. Exercise meant Foreman exits. All

[00:24:17] Host Create clip right, I know you're not prescribing anything, but, uh, how many days are you taking it? How many days you're not? How often are you exercising? How often do you not,

[00:24:28] Host Create clip Um, actually spent a lot of my thirties and forties not exercising at all. It's crazy, right? Someone like me. But I've become better at it now that I'm you know, I was approaching 50 now and 50 s o. I spend about four hours in the gym on the weekend with my son Benjamin.

[00:24:44] Host Create clip Do like, two hours a day,

[00:24:45] Host Create clip no, four hours straight. But it's not all exercise. Okay, so it's an hour with my trainer, Shawn, who does mostly combination of weights and stretching. Um, some free weights, some machines. Then it's another hour on my own with my son. We do some treadmill, some more stretching and essentially just muck around and doing stuff that it's fun for him. And then we also then we d'oh some some yoga downstairs in the gym, a little bit of relaxation, but the best fun part that I really love is at the end. We do a sooner hot tub. Colbert s on a hot tub cold bath for about an hour, and I feel fantastic. Often

[00:25:26] Host Create clip talked to me about that. So in your book, you go into cold exposures. Did you move the Boston? It sucked coming from Australia and you bundled up. And now you wish you hadn't, Um Why cold exposure is cold and hot, both necessary. What's the?

[00:25:39] Host Create clip Well, there are a few reasons. One is the high level view is that anything that stresses your body puts it into a state of shock is good in the long run. But a little bit of perceived adversity being a little bit too hot, little bit too cold. And especially the Grady in between those two, Which is why we jump from one to the other. The next point is that I've looked at the literature and at first, when I was prompted by my publisher to look into this scientifically, they said, you know, what about this cryotherapy? What do you think? And a couple of years ago, I had no idea that this was real. It sounded like bullshit to me. but I looked into it. And there there are two important things. One is cryotherapy, or cold exposure will build up what's called brown fat. We didn't know brown fat existed in humans until about five years ago. Typically, it's across your back in and all the reasons you can see with a pet skin. But otherwise it's pretty invisible. Just looks like fat but brown fats particularly healthy because it it has a lot of mitochondria. And we think it also secretes little proteins that tell the rest of the body to be healthy.

[00:26:40] Host Create clip In what way to be healthy? We're not sure yet. We're not sure interesting, but men, I want the answer, that question.

[00:26:47] Host Create clip But it certainly revs up your metabolism and will burn energy if you're looking to stay lean. Having a bit of brown fat is is all good. So my friend Ray Cronus and I have written on this and Andrew Bremer it. And at the N. H. We call it the Metabolic winter Hypothesis and essentially it, saying that you know, lifestyles these days were always warm. I'm wearing this jacket. We sleep with the covers on we turn up the heat. We never get exposed to cold unless we force ourselves to. And we think that that's possibly largely responsible. If not, you know, maybe partly. Perhaps largely responsible for the DYP. Diabetic problem we have what's okay. So if if you're cold at night, you're gonna burn a lot more energy. Staying warm? Yes. Turn on your brown fat. Now, that's gonna keep people lean. If we bundle up and and we eat the kind of diets that we see in the supermarket, that's gonna be doubly bad for our bodies. Yeah, where? Warm. We're not losing energy. And we're eating a lot more.

[00:27:46] Host Create clip Yeah. This is this stuff. It's so interesting. Okay, so what's your advice? Whatever you're about to tell me. No, I'm going to do it. So, like, uh, how frequently do I want to be doing it? Is it every day? What's that look like?

[00:28:01] Host Create clip Well, what I do is because I'm busy and I don't have a sauna or a cold tub at home. I subject myself to this stuff for about an hour on Sundays on What I do is I spend about 15 minutes at 100 and 50 degrees Fahrenheit. Well, that's reasonably intense, but you get used to it. Then we go into the steam room. Um, we were sitting there chatting. It's great temperatures lower in the steam room because humidity is saturated in the roofs dripping on you hot water, but that that I don't know if the steam helps. But I suddenly love the feeling of being in there. And my skin starts to be healthier because, of course, it's cleaning itself out. And then the final thing I do is hot tub, pretty hot, hot water. And then and then I go and dunk below the water a couple of times in water that's less than four degrees Celsius. So that's so cold that it takes your breath away. Yeah, yeah, that's great.

[00:29:00] Host Create clip Interesting. Was there anything else on Level three that we should know about?

[00:29:04] Host Create clip Yes. So work that we've done recently, just in the last year is finding ways to tweak the cells and the tissues of mice, at least to reset the clock. We've been working for 10 years, as I said, accelerating the clock, we can drive that hand of the clock for words. No, we we cut the DNA of the animal. Let it heal. And in doing so, we distract those proteins from where they come from somewhere disturbing this survival circuit so much that we disrupt the spooling of the DNA. And what we got was an old mouse by every account based on histology, which is looking the tissues based on their physiology. They got grey, they got arthritis, they got heart disease even. And when we look at the molecular clock that methylation clock, they were 50% older

[00:29:53] Host Create clip community. They had Maur like clumps everywhere. Those method groups were added to the DNA. Right. Okay,

[00:30:01] Host Create clip so we had given them heart disease and Alzheimer's or dementia. We've given them all these diseases, but by measuring the clock, what we had actually done is give them aging. But that was the first step that took 10 years. The last year we've been asking, How'd you get the hands to go backwards? That's a lot harder, but we were fortunate that the 2012 Nobel Prize was one for the ability to reverse that clock in cells. It's called was the prize awarded to Shinya Yamanaka, a Japanese fellow very smart guy, and he found at least four genes that when you put into, say, skin soles of an adult, if you gave your skin cells, I could go back to 11 basically clone you. I could take yourselves, make a stem cell pool and I could grow you into a new little liver or new little kidney. That's all easy. Not easy, but it's doing well. It's doable. What that tells us is that those for Yemen are cute. Jeans can reset age if I can take someone who's in like you, who's in the early forties and make a new you as we've done now for many species are dogs, cats, sheep, monkeys, those animals. We can reset the clock 100% and those animals actually live a normal lifespan. That tells us that the instructions to be young are still in the cell somewhere, as though there's a backup hard drive that tells the EPA genome. Those spools had to go back to be young again and get those methyl groups back to being young again. Not up here but back there. But don't strip him off too far to be a stem cell.

[00:31:32] Host Create clip Well, basically, turn you into the world's giant tumor.

[00:31:37] Host Create clip Uh, okay, so one. Why did I become a tumor? Because the tumor is a cell that doesn't know to stop. So what is it that you're breaking in that process that that makes it so, um dysfunctional? Yeah.

[00:31:49] Host Create clip So in terms of the clock, let's just start with that Shinya Yamanaka round the clock so far back, it went back to zero back to midnight that we do not want to do because the cells lose their identity. And that's the last thing we want to do. We don't want to go back to us

[00:32:03] Host Create clip because it's dangerous to have a pleurisy potent stem cell in the wrong place in the body. Of course it'll grow. It won't stop growing. But why doesn't why? Why does it become a tumor? Why doesn't become a liver or along like I would get the problem of having a liver developing my brain. But I'm just saying, like, Why does it become a tumor cell instead of an actual functioning liver?

[00:32:22] Host Create clip Well, so when you go back far enough and it loses its identity, it will just multiply into a mess without cellular identity.

[00:32:33] Host Create clip So there's something else going on that stops it from figuring itself out.

[00:32:36] Host Create clip Right? So in the lab, if we take a pluripotent stem cells and we want to make a liver cell or a neuron a nerve cell, we give it a bunch of chemical signals in what we call the niche. When one of these cells lands in a niche around those old cells, they'll use that stem cell to rebuild tissue. But imagine if we could reset the clock, not all the way back to a stem cell, but just partial. Reset the clock so so that you could go back to being 20 again. That's what we're able to do in some tissues in the mouse right now. You

[00:33:05] Host Create clip do it on mass when its cell by cell DNA strand by D n a strand like How the hell do you get this to take effect through a whole joint? Little in the whole body? Yeah,

[00:33:17] Host Create clip right now, the way we do it is we inject a virus called in a V, and this virus will target certain tissues and deliver the genes to most of the cells in that tissue, for example, we are treating aging of the eye in my so we can take an old mouse. We deliver a virus theeighty into the IEDs and tiny little prick. It's the same virus that that's used to correct genetic deficiencies in the eye. Right now. FDA approved drugs. So this isn't science fiction. This is out there in the world right now. We give it, give it to the old Nice. We give them an answer about it. And nobody called Dr Cycling. Okay? Same thing you might take if you got Lyme disease. And that turns on these reprogramming factors. We don't use all four of the factors os km nickeled because one of them causes cancer. The M we leave off the m, we put o s and K into the I turn it on, leave it for a few weeks. Measure what happens to the eye. And those mice can see again like they were young.

[00:34:20] Host Create clip So we've tested three different types of damaged damage to the eye. The 1st 1 we did was a Hail Mary, so that a lab near ours across the road works on rejuvenating the spine and the optic nerve just raysy. Yeah, because we know as soon as you're a couple of months old, you're not going to re grow a spine. It's one of the first part of the body that age is in vain. But jellyfish can regrow. Excell levels can regrow an arm. We lose that ability when were very, very young. So the question was, if we turn the clock back a lot without os que genes, will those nerve cells be young enough to regrow back to the brain if we damage them? And that was the experiment. They pinched the back of the optic nerve so that the nerves were defective and they started to die back towards the brain, caused the mice, lost their vision. We then turned on our reprogramming factors. We now see that the nerves yet young again wind the clock back and they re grow back to the brain.

[00:35:15] Host Create clip We could give ourselves the healing ability that we only had when we were embryos. And you start to think about what could this lead to if we can do this safely? Of course, safe is the important word across the body. Imagine, one day you could have every cell in your body able to be rejuvenated like that. You cut yourself, you break a bone you lose your your mind, you have a dementia. You take a course of doxycycline for a few weeks and stop. Switch it off again. And you, you, you heal if you turn it on at high levels. There's a lab in Spain that has shown that you can get small tumors in some animals in the kidney, so we've been very careful to not just blast the cell with these factors. Permanently, we've tie traded what we say brought the levels down to very low levels and switch it off when we don't need it. But we have given mice this virus throughout the body. We injected into a vein and we turn it on. We've left it on now, expecting the mice to die a year later, that perfectly fine. So it appears to be safe. But of course, there's a lot more work to do. I'm a scientist and I'm developing drugs. I have to be very aware of the dangers.

[00:36:20] Host Create clip Please, nobody go out and try this at home at all until we know more. But the ISA good testing zone because it's protected, and if there's a problem, it's, you know it's shielded from the rest of the body. It won't go too far. But everything we know now is that it seems to be very safe, at least in the eye.

[00:36:37] Host Create clip Wow, this is crazy. So that is Is there an element of getting better improvement, human performance or anything that you can tease us

[00:36:46] Host Create clip with? Well, we've actually published results that in mice if you give them a nen 80 booster molecule that will turn on these Pacman enzymes called sirtuins those mice, when they're old, can now run 50% further. In fact, some of our old mice rent so far that the treadmill stop because my son not supposed to run more than three kilometres, We

[00:37:08] Host Create clip haven't talked about any d yet. Tell me what any D is what the precursor is howto I supplement for It

[00:37:15] Host Create clip s oh, there are a few on the market. I don't endorse Oh, sell anything just by the way. Even if you see me on line, that's not me. So that said there are There's one called NR which is Stan which stands for nicotine in my driver side, which is a very early precursor to making an A D in the body. There's an intermediate from that cold. Any men not to be confused with Eminem's Please don't do that. That's not healthy. And then the cell turns enemy into N a D. And you can take all three, actually, or each one of those three and raised in 80 levels in animals. And now we're doing myself and many others are doing human studies. And we've seen that in our and in my case, and a man does raise the energy levels off older people and young people are like up to levels that we think you could really achieve. Even with being a marathon runner.

[00:38:09] Host Create clip That's crazy. So just tow. Bring this home for people. Talk to me about your dad and his end of one experimentation with N m N.

[00:38:17] Host Create clip Yeah, so my father has been on the same regimen is me resveratrol for over a decade, the red one molecule. He's been on metformin longer than me because he had. He was a borderline diabetic, type two diabetic. Ah, and he's also on Enemy. And now, and he seems to be doing great. He's now 80. When he was in the seventies, he was slowing down his. He was starting to say the same things twice. You know, typical 70 year old he's doing right now. He's 80. He's got a new lease on life. He started a new career down in Sydney. He's high king of the world right now. He's traveling around America, driving his elderly friend around. His friend, unfortunately ended up going to the hospital the last few days. So my father is taking care of his friends, who he's seeing on the decline on. And he's if anything, improving every year.

[00:39:05] Host Create clip I'd love to hear more about resveratrol, which is something that I've completely written off. Until I started researching you, it seemed for a red hot minute, like it was really and then it seemed toe completely die. And I know that you got sort of caught in the middle of some of this stuff. So where has all this forget, like what pop culture thinks of it? Like, what's the reality of Yes,

[00:39:27] Host Create clip or resveratrol was a proof of concept molecule back in 2003 the first of its kind that could mimic Clark restriction, make mice healthy on a high fat western diet, and it was it was a great proof of something that we were trying to figure out, and it led to drugs that went into humans. That looks really promising. Um, I got embroiled in a scientific and a corporate war soaking in the case of files are they put out a scientific paper that said, essentially everything that David has said is wrong. Okay, And then that was a great headline. Harvard scientists started companies is wrong. Okay. And, you know, and then I spent about a week in bed saying, Fuck the world, You know, why am I doing this? Why am I working so hard for society if they don't care? But I worked my way out of bed. I thought, Let's dig deep and see if they're writing or if we're right. And so, for another three years, we really worked hard in my lab at Harvard to test whether we were right. So the question was, with this Pac man, that spools the Dina, Does resveratrol work on it, or is it working on something else? And that to scientists is really important, because if it's not working on this, all the drugs that were trying to work on this are probably working, um, the wrong way that we thought to cut a long story short what we found and published in the journal Science, which is one of the top you can do.

[00:40:48] Host Create clip Um, and I say that because it's validated. Science is that we showed that resveratrol does binder the Pac Man, and it is responsible for this. And we now have new information that we haven't published. But I'll tell your audience about it. We've made a mouse that is resistant to activation of the Pac Man. We can tweak the enzyme just in one amino acid in their protein out of about 1000 that blocks this movement activation. It's normally chewing like this. What if we had resveratrol toe a normal mouse? It'll do that to our mutant mouse. It's this which is better with the rapid munching, rapid munching is better. Okay, as the rapid was, we think was responsible for the health benefits and the longevity.

[00:41:30] Host Create clip So what you're showing is by slowing it down, you cause real problems and thusly. If you have resveratrol in there and get it munching really fast that you've done something

[00:41:38] Host Create clip positive, right and our mutant mouse should be resistant to the benefits of resveratrol if we're right. But if FISA is right, then resveratrol should still provide benefits. Even though this enzyme is working on some some other way. Got it. So the mouse that could not be sped up. The mutant mouse does not live longer when given resveratrol on its high fat diet. Interesting. So that will be the punctuation mark. The F you were right. But interestingly, the world has moved on. Right? Well, I'm left to clean up the pieces,

[00:42:09] Host Create clip right? Yes. So And when you say the world has moved on, you're talking about people like me who just assumed that it was garbage and that it's not riel. OK, so you've said that the only supplement you take his vitamin D. Um, so how are you getting resveratrol in the system? Is it a drug? You have to have a prescribed.

[00:42:27] Host Create clip Well, I'm taking this virtual I have.

[00:42:29] Host Create clip And what we call that a supplement. So and it's commercially available.

[00:42:34] Host Create clip It is. If it's a legitimate cellar and it's 98 plus percent pure that it seems to be similar to what I take

[00:42:42] Host Create clip and ballpark. How much do you take?

[00:42:44] Host Create clip I take a teaspoon into my yogurt. That's probably close to a gram

[00:42:48] Host Create clip every day, every day. Yeah. Okay. Uh, resveratrol. Roughly a gram. Are you taking Mmm. Or is N m n? Or is that just your dad? Ah, both of us. Okay. And then, um, met Foreman, right? Those three. Anything else?

[00:43:03] Host Create clip Those The main things that I think are helpful. And I've been monitoring my blood by chemistry. So and

[00:43:09] Host Create clip he said you took an M arrive. You're hurt, right? Which I love. Uh, what are things that we should be testing assume for a second? I'm I'm willing to go all the way. Do any crazy test enough what I'm doing. It's working. Um, what would you recommend?

[00:43:23] Host Create clip Well, I avoid X rays and CT scans unless I have to. Sure. Right. If your doctor says go for it, please don't refuse that. But otherwise, don't do it for fun. Don't do it because you're curious, because those CT scans will break your DNA and we break the mouse's DNA. It's it's aged. Goes up by 50% So whoa, Right. So avoid Dina breaks as much as possible. What I do is I take a blood test from a company called Inside Tracker, which in full disclosure, right I invested in years ago, and they look at about 30 parameters in your blood and give you feedback. It's Dr Supervise, so it's it's legit and it's based on a lot of science. And that at least gives you some feedback about your body about what's actually happening. If you change your lifestyle or you take a supplement or even a new drug, for that matter, so you gotta have you gotta be monitoring cause you don't you don't want to fly blind. You don't know if for you you're doing harm or doing good.

[00:44:17] Host Create clip So do do a blood test. At least go to your doctor and have a blood test for for a good goodness sake, you could have your genome sequenced or do something that looks at the variance in your genome for relatively little cost A thing. It's $99 Now I gave a test of that kind to my whole family as Christmas present, and what we've learned is that some of our members let members not let members. Family members have variants that predict longevity. Some don't Some have mutations in the genome that are a little bit scary. Um, down the line, you could get your DNA methylation age determined the true. What's called the Horvath clock? Some people measure the telomere lengths. Um, just

[00:45:00] Host Create clip did you a biopsy to do that, Or can you do it from blood?

[00:45:02] Host Create clip What? Blood test is fine? Yeah.

[00:45:04] Host Create clip So interesting. All right. Where can people learn more about you?

[00:45:09] Host Create clip Ah, well, so that the main site is life span book dot com. That's where you can sign up for the newsletter and bye. Copy the book. If you're interested,

[00:45:18] Host Create clip I highly encourage it.

[00:45:19] Host Create clip Thanks. I'm also now on social media. So have a Twitter account. I tried to talk about the science about new findings about things that I've just learned and stuff like this that they might want to tune into. My Twitter account is David A. Sinclair, and I have instagram where I send out some, you know, little fun to do is not to do this kind of thing. And that's David Sinclair PhD. OK, what's

[00:45:43] Host Create clip the impact that you wanna have on the world?

[00:45:45] Host Create clip Well, that's easy. Since I was four years old, I've wanted to figure out why we die so fast. And you know, in my view, I think it's cruel to have a sentiment being that knows it's gonna die in such a short time frame. 80 years is nothing. It goes by in a blink of an eye. Even 1000 years will go by in a blink. It's only 20 times what I've lived, so I want to be able to leave a mark on the planet. I'm hoping to have moved the needle somewhat on the course of human history. I think we've come further than I thought we would in my whole lifetime, and I've still got a few years left to try and make what I'm talking about come true. I

[00:46:19] Host Create clip certainly hope so. If you were gonna have people make one change that would have the biggest impact on their health, what change would you have them make?

[00:46:26] Host Create clip Well, so having read tens of thousands of papers and done this final 30 years and talk to people and I know what's on the cutting edge, the simplest thing you could do that would have the biggest bang for the buck is be a little bit hungry, donate, but that's not to say beat Mel, not nourished. Don't don't starve yourself, right. There are a lot of teenage teenage girls, a particularly who don't need enough. So I'm not saying that at all. You've gotta have a minimum nutrition, but for those of us myself included, who likes to eat those of us who don't mind a bit of dessert try to skip a meal. I skipped breakfast. Besides that bit of yogurt. Often I'm too busy to eat a little lunch at dinner. I eat a normal meal. I don't gorge myself because that'll trigger all these defensive pathways that will rebuild the body. Or at least keep it pristine until we have such things as the Level three reversal which we're now working on.

[00:47:18] Host Create clip That's amazing. Thank you so much for being a pleasure. Incredible. Guys, read the book. Dive in. If you're like me and you wanna live forever, I'm telling you, this guy is at the tip of a very exciting spear. So check him out. If you haven't already be sure to subscribe until next time, my friends be legendary. Take care, man. That was fucking awesome, Everyone, You all know how much what you eat and drink matters literally. What you consume affects you on a cellular level and dramatically influences your overall health. T has been shown to naturally boost energy levels and provide immune system and gut health support. And given what Lisa has been through, I can tell you firsthand that focusing on your gut health is critical. He can also contribute to mental performance and may even help of longevity. You had me at hello with mental performance and longevity. Petey makes some of the most convenient, easy to use. Healthy tea's on the market Pts are made from organic high quality leaves and ingredients from around the world and pique tease deliver 12 times Maur antioxidants than any other T Pts are also triple toxin screen for heavy metals, pesticides and toxic molds. And my team here swears by PT they love this stuff. The guy behind the camera is literally fist pumping right now because he drinks too much of this stuff. Petey packets are super convenient. They dissolve and hot or cold water and air perfect for traveling or the office, or when you just have to grab something on the go. And right now you get 17% off their teas, plus free shipping by going to peak t dot life forward slash impact again, that's peaked. T dot life slash impact and Peak is spelled P I Q. U E. Go there now to get this special discount and check out the description below, or just click the link and get your peak T today. Check it out, guys. Enjoy and be legendary. Take care.

[00:49:21] Host Create clip Thank you guys so much for watching and being a part of this community. If you haven't already be sure to subscribe, you're gonna get weekly videos on building a growth mindset, cultivating grit and unlocking your full potential.