“Age Reversal Is Coming.” Inside The First Human Trials - Dr David Sinclair - #1141

the first ever podcast episode that I recorded in America was with you. In 2019, Harvard Medical School, in your office with what looked like the illustration of a snail on the whiteboard. And it was filmed on two iPhones, one of which I'd had to borrow from a friend and a single white USB microphone. And that was over 70 years ago. Yeah, I know. Remember it well when you were 12, right? I was 12, yeah, correct. Yeah, it was very clear. And from those days that you were going to be a big success, a smart, driven, came prepared. And look, this is beautiful now. Full circle. Yeah, I didn't realize Starbucks Venti has way more caffeine in than the British equivalent. And it took my fucking face off. I was obviously trying to think about the Yamann Archefactors and how important NAD and Resveratrol in Yogurt is, meanwhile, my whole body was vibrating. But you know, you've done maybe more than almost anyone to make the biology of reversing aging a part of mainstream conversation. So I want to talk about kind of everything that's happened since we first sat down. The Yamann Archefactors, what's happening with NAD and Resveratrol, news discoveries, before we get into that, though, what discoveries have excited you most since 2019? Gee, a lot. I'm very lucky to have a lab where there's up to 40 people running around making discoveries. I go back there to recharge. It's like the Willy Wonka. You've been there. So you know what it's like, it's unparalleled. I wish everyone could come visit. The highlights would be, so in 2020, we published on the cover of Nature magazine that we could reverse aging safely in an animal for the first time, a mouse. We could, it's blindness. That was pretty big. Cover of nature, it's what most scientists dream of in their lifetime. So that was pretty big high. Since then, it's been rewarding to see that it's been repeated, not just by other labs, but in different animals, monkeys. It's been working in different tissues, so it's not just the eye anymore, where we first tested it. It's pretty much working in every part of the animal's body. And then the big thing is we've now gone into people. So there are people getting their, hopefully, their age reversed in their eye to cure their blindness or at least improve their vision at the very least. Why start in the eye? Yeah, good question. This is a gene therapy. So we're introducing genes that are very powerful. They're called Yamannarchaefactors. You mentioned them. But we use a subset of them that don't cause any trouble. If you just use what Professor Yamannarchae used, it's not going to be very healthy. It's actually quite dangerous. So we use a subset of those and we deliver them with a little virus-like particle. And the safest way to deliver a virus-like particle into a human is to go into a space that's enclosed. It's not going to spread. And the eye is where it's most being tested. And so we did it for safety reasons, not because it would work better in the eye. In fact, I told my student at the time, one check, that he was crazy to try to cure blindness. Why not do something easier like the liver? But he said, you know, the eye is probably the best place to start for safety reasons. And he was right. I remember that though. That was, we were talking about that in 2019 when I was in your lab. What has, there's been this recent release that came out last month. What's that? Why is that so special? Though one about that we've gone into humans. Well, I think most people thought the aging field was a lot further behind. Age reversal, you see online, oh, we've done this in human cells. We've done it in a mouse. But suddenly, there are people now getting what could be the world's first true age reversal drug. So for us, it was old news. We'd been doing this and expecting it for a while. In fact, we made the discovery back in 2016, 2017. So it's for us, it wasn't so, so amazing. But for the world, I think it was a shock to hear that people are actually getting this potentially age reversal drug for the first time. What would be the issue that somebody has in their eye, which would be reversed? What's the, the sort of patient that this would face? So this is the, the thing that makes me super excited is that every piece of it, or type of damage and disease that's, that's been tested in animals, not just mice, but larger animals, it's work to improve the vision of either a disease or damage. So for instance, if you pinch the nerve, you laser it, or you give a mouse glaucoma, pressuring the eye, we can treat that effectively. And nothing reverses blindness currently, except for this treatment in animals, even. And so that's what's exciting, even macular degeneration glaucoma, the two leading causes of blindness in the world. Both of them are really, really easily treated by this new mechanism. We call the drug ER100, which is epigenetic reversal 100. But yeah, pretty much any disease or injury could theoretically be fixed treated by this technology. Any, theoretically any disease or injury could be treated by this? Well, in the eye, but even beyond that, the liver, murder neuron, so ALS, the brain has been reversed in aging. Memory comes back. Even joints, there was a Chinese study that came out recently, looked very good. They used our technology to rebuild bone and cartilage in, in osteoarthritis. And so, you know, I don't know anything else that just rebuilds body parts like this. Can you explain how it works to a simpleton? Not you, but I don't think anybody listening is a simpleton, but it's actually quite simple that the good news. We take three genes that are normally turned on early in life. And these three genes make factors that turn on a cascade of events that the cell uses to reboot itself. The simple way to think of it is that I hypothesize that the body has software that gets corrupted as we get older. So an old person still has information there. It's just that it's been corrupted the software. We call that the epigenome. It's separate from the genome, which is the DNA. The epigenome sits on top of that and controls the DNA. So in my book lifespan, it's a little dated now, but you might remember I chose a CD as the analogy. The epigenome is the reader of the music and the DNA is the music itself. An aging is a scratch CD. So for those listeners and viewers who don't really know what a CD is, they're really cool things we could put 20 songs on. But a better analogy now would be your phone has software. A really old phone is slow. It can be corrupted, can get overused. And so we can reboot that. And we found that these three genes that we put in, which we call OS and K for short, these Yamunaka genes, trigger a program that embryos normally use to reset their age. Or something very similar to that program. Something you might not know, most people don't know this, is that when we're fertilized, and we've all been fertilized, we wouldn't exist. And then we need to reset this epigenome. The software needs a reset to go back to being young again. And that happens. No way. It's a fact. It's shocking, but true. Young, very young embryos are old, and then they get reset. So the software is really, it's not software. It's the way the DNA is folded in the cell. And every cell has to compact the DNA because it's six feet long, has to fit into a microscopic little ball. And how that's compacted depends on what kind of cell you're going to get. So if you want to make a nerve cell, you compact different genes. And when you compact them, they switch off. But you need to read nerves that make nerve cells so you open those up. And this bundling and opening of DNA is what the epigenome does. And my theory, called the information theory of aging, said that this pattern, pattern of bundle loop, which is different for every cell type gets corrupted, gets eroded during aging. And that literally is aging. And we tested this and published it in 2023. And we created a mouse where we could disrupt those loops and bundles. And the mouse's cells lost their function, they lost their identity, the nerve cells forgot how to be nerve cells. And the mouse literally got old. We could speed up that process by corrupting that software, the epigenetic software. And then when we did that, which took us 13 years, we started working on reversing that process, which is how we get to here. People see aging as a certainty, but you call it a disease. Is it truly a disease, or is that just a useful metaphor? Well, it's just a word really. So we can call aging whatever we want. But I prefer to think of aging as a disease. Because otherwise, we're not really treating it. Most doctors don't think of old age as something that is preventable or treatable. Even though now we believe we understand that it is very treatable, or at least slowable. So I think it's a useful way to look at aging as something that we should address, even starting early in life to try to slow it down at least. We all need to stick around for longer because the technology that's coming is incredible. And I proposed this in my book, and even put it on the back cover. And it was a lot of people were telling me that that's crazy. Don't say that, David. It's going to be scandalous. People are going to not take you seriously as a scientist. But I'm glad Matt, my co-author at MATLA Plant, convinced me we should go for it. Actually, That was his main role, besides writing, was to say, "David, just do it because don't worry what your colleagues will say because some of them can be pretty brutal." We put it in there and it's seemingly been embraced by a lot of people and now you hear it quite often. What's the technology that's coming? If that's what we've done so far, what do the next few years have in store for us? Well, there's a fork in the road, I don't know when it's coming, but it's similar to the singularity with AI or AGI. When we show, and it's a matter of when, not if, that aging is reversible in humans, because it works in all these other animals, it'll work in us where basically just slightly more intelligent monkeys and it works fine in the monkeys. That's going to be a turning point, I believe, for humanity. There'll be a lot of people who say, "All right, now let's get on board. Let's invest. Let's blow this out of the water." There's already a lot of billions of dollars put into this, but it's going to be big like AI when that happens. These technologies, let's say it works in the eye and now we can treat perhaps cure most types of blindness. Then we're already doing this, I can't talk about too much, but we're already looking at other tissues, the liver, for example, and maybe there's joints and hearing that we can also repair, ultimately where this is going, obviously, is whole body reset. We can do this in mice, easily, in my lab now, and others have done this, and they've gone-- Every cell in a single organism. We don't have the technology with the viruses and the genes to reset every cell, and that's a limitation of getting the genes into every cell we can't do that. We can basically, at best, get it into half of the cells, but still a lot of them. We've taken a path that's a little different now, you know, I was saying we've been doing this for a while, and the world doesn't really know what we're up to in my lab. I can reveal that over the last five years we've made breakthroughs in turning it into a pill, that's the next big thing that'll come out of my lab is revealing that we can give a mouse, an old mouse, something orally, so they don't show on the pill. We give it down their throat for three days a week for a month, and we see that they are rejuvenated in many ways, including not just their memory, but things like even their skin quality. What's happening, what's the pill doing to them? Well, that's a lot of work. We're still trying to figure that out, but we know it works, but you don't necessarily know why or how it works. Well, we actually literally don't know how the genes there in the eye of humans now work, really. That's a big question in my lab, I was trying to answer, where is this backup copy of software, but we do know it works. That's the hard part. Then figuring out how it works will be important to make these drugs even better and more powerful and more potent and longer lasting. What we do know is that the epigenome is involved in the pill, not just in the gene therapy, because we can disrupt that polishing of the CD or the reset of the software. There are genes called tets, which make proteins that strip away chemicals off DNA. These are key to the epigenome reset in embryos, as well as in our bodies. We can get rid of them or inhibit them with a chemical. We can feed those to the mice or give it to the cells. We have some good evidence. I hope my students don't kill me for saying this publicly, but we do have good evidence that the pill, let's call it, the cocktail does work through this epigenetic thing. It's not just all the cells are getting stressed out by the chemicals and they fight back and they live longer. It's not that it's truly through this reset mechanism and we can show that by getting rid of these tets enzymes that strip chemicals off the DNA. Without that mechanism, the cells don't get younger, even with the chemicals. Do you think there's going to be a realistic upper bound to human life? Well question is when. I think that ultimately there is no up-o-limit to human life. I just visited a bonsai garden in Japan where the trees are a thousand years old and that's they're not even halfway through their life, so biology doesn't have limits. It's just a question of what our genome encodes in our epigenome, but you know, we have control the century over our own biology. We don't have to just be at the whim of what evolution and the serengeti gave us. And I see no upper limit, doesn't mean I think you and I will be immortals that's right now beyond our imagination. Well, it's definitely imagination, but to be on technology that I can think of. But I do think that some of us will have a chance to live decades longer and probably the first person to live 250 years already alive. First person to live 250 years already alive. Yeah. I'm not the only one in my field saying that it's now realistic. I mean, think about it this way. It's hard to imagine the future, right? But a kid born today is going to live into the 22nd century. And we can't even imagine what the world's going to be like 10 years from now. So the longer you live, actually, the longer you get to live. Surely if someone took age reversal pills for long enough, they'd just become a baby. Is that another way it works? Well, we made sure that wouldn't happen. That was one of the things that one changed my direction. Benjamin shot everybody into it. Yeah. Well, that was the trip. But Yamanaka, Professor Yamanaka won the Nobel Prize for making cells go back to age zero and making them into stem cells. But that's not going to help us. We don't want to strip away the identity of all our cells. We'd die within a couple of days. And in fact, if you do that to an animal, it's tragically does die or gets cancer. So what took us the longest time from 2014 to 2017 was figuring out how to reverse aging, but not so much that it loses the identity of the cell or erases it. And my student, One Cheng, famously almost quit the project. He was doing his PhD. He was in his last year and nothing was working. He was either having no effect on the human cells in the dish or they would be becoming cancerous. And he said, David, I don't know how to stop it halfway. And we came up with one last experiment that thank goodness it works because we wouldn't be talking about it now. We tried a subset, just three of the Yamanaka genes. And leaving one of these Yamanaka genes out was key. Without that final gene, it's called CMEC, we call it M. Without M, the M gene, cells don't go back 100%. They go back about 75 and stop. And that was the breakthrough. The stop was really hard to find. But it's there. It's just turned everything into stem cells. Yeah. It's even worse. Well, maybe not worse, but it's definitely bad. You're not going to live longer or cure blindness. But that was a breakthrough. And One Cheng sent me the pictures of the cells that we younger and said, Eureka, I think we've done it. And it was a remarkable thing to witness. What do you think most longevity experts secretly believe, but can't prove or once they publicly at the moment? Gosh, that's a good question. I was going to say most of them secretly think that I hyped this stuff way more than I should, which is, again, not a fair thing, because my lab is eight years ahead of what we've published. But I think most aging researchers, I can say for a fact, behind the scenes, say, this is going to be much bigger and more powerful than we expected. I've been told by some of my colleagues, don't say that number 150. It makes us look bad, and I'll say, well, do you believe in it? Yeah, but we can't say that because we're scientists and we'll lose credibility. So yeah, I think a lot of the scientists are very cautious by nature, by the profession. I'm considered an outlier speaking my mind and what I believe in. The most scientists don't cause it, it's not something scientists typically do. Why is it that your scene is an outsider, are you throwing more caution to the winds than other people? Is it their criteria for evidence? Is different to yours? Is it that your lab has got access to information that other people don't? Well, there's a few reasons. It's definitely that my lab has information that nobody else knows, and that's been difficult my whole career knowing that something's true, but it's not published yet. So in the minds of my colleagues, it doesn't exist yet. And in fact, my book came out in some cases years before we published the work. So the public knew my lab's work before other colleagues had seen it. That's also rare. Another reason why I'm a bit of an outsider is I'm not doing this to be a scientist. I'm doing this because I'm on a mission and my life is irrelevant. I would literally die to achieve this mission. And so if I get criticized, if I speak my mind, I really don't care what's the mission. To impact in a positive way as many lives as possible. This was since I was four years old. My grandmother gave that mission to me because she lived through World War II and the aftermath in Europe. And she told me the horrific things that humans did and can do. And she was always saying, we can do better as a species. And I feel like I want to die knowing that I've done the most for a humanity that I could possibly do. And if it upsets a few people, I don't care. 75 vitamins, minerals, probiotics, and whole food sourcing ingredients in a single daily drink. And that's why I've been taking it every single morning for nearly five years now. And they've taken it a step further with AG1 next turn back by four clinical trials. Nurse trials that was shown to fill common nutrient gaps, improve key nutrient levels in just three months and increase healthy gut bacteria by 10 times, even in people who already eat well. Plus, if you're still unsure, they've got a 90-day money back guarantee, so you can buy it and try it every single day for three months. If you don't like it, they will give you all of your money back. Right now, you can get 20% off a welcome kit and that 90-day money back guarantee by going to the link in the description below are heading to drinkag1.com/modernwism. That's drinkag1.com/modernwism. Long jeopardy is a huge field, right, includes everything. When you think about all of the different types of interventions that people can do, how do you chunk them into groups? Sort of what are the buckets that people should be thinking about is contributing to their lifespan? Yeah, so I talk about this on my YouTube as well. So, there's a lot of detail on there now and I've relaunched it. He's here. Congratulations. Welcome back into the fray. I'm glad that you've stopped doing the wasteful work in your lab and gone into the serious work of YouTube videos. Yeah, I was working on solving aging and now that the clinical trials have started, I'm back to more important things. Back to being an influencer. More important things. But yeah, so what we talk about on the podcasters, what are the major things that people can do to slow down aging and even reverse aspects of it? But if we've got this technology coming soon, your eight years ahead, everybody is doing the longevity escape velocity bet for every day that I live. There's more days that I can hopefully live. So, in the interim, those are the buckets, right? That's the stuff that people need to focus on now. For sure. I think anyone that doesn't focus on their longevity might miss the boat. It'd be tragic if you died a few days before, some of these technologies came out. And this is, I'm not worried about you killing over any time soon, you're very fit. But, you know, your parents, your grandparents, think about them. Try to encourage them to live the healthy lifestyle that we're going to discuss now. The buckets are lifestyle. So within that, there's the obvious things that we can talk about, which is what you eat, how you move, how you rest, your stress, these kind of things, that's what you can do. And you should do it on a daily basis. It's what I do. Then there's drugs, which some of which may work. So that's metformin, repamise, and some senolytics. And probably GLP1, receptor agonist, would fall into that bucket. And then there's supplements, which is the Wild West. There's a lot of things said about them. I believe in a few of them, based on a lot of animal research and some human data. Those are the three main things that you should do in your daily life to maximize your chance of getting these medicines. OK, lifestyle stuff. Last time that we were talking, it was all about calorie restriction and primarily fasting as a root toward calorie restriction. How should people eat, if they want to live as long as possible now, which is 2026 data? Well, actually, what I've been saying, actually, I'm on my podcast for now, what, four years, it hasn't changed. And my book, Lifespan, which came out, we were talking about when we first met in 2019, nothing in that book, I've had to revise. It's all considered-- There's no retractions from the book in 2019. No. And my labs never retracted anything. And at this point, never been proven wrong, which is a blessing. And I knock on touch on wood. But that's good news, which means that the things that I've said before, people can go back and learn still. If this is the first time you're seeing me, let's start. So the main things about fasting are, we know from animals. And some human data, mostly from animals, that if you restrict how often you eat, and to some extent, how much you eat, you get longevity benefits. And we can talk about protein ratio to carbs to fats. That's also a whole big debate, as you know. But generally, I like to eat one meal a day, maybe two, if I'm being social, but not three. I think three meals a day plus snacks is marketing. Breakfast being the most important meal of the day was general meals, I believe. One of those companies, Kellogg's, perhaps. But this is, you know, it's all marketing. Humans are not built to eat that consistently. I don't think cavemen were sitting around eating their big breakfast saying, what are we going to eat for lunch? I think, you know, maybe if they just killed a mammoth, but generally they were pretty hungry a lot of the time. And our bodies have adapted to that. We're not meant to always be satisfied. And so I try to be hungry. And if I gain a little bit of weight, sometimes I travel and I eat well. And Serena and I, we do sometimes love to eat. I'll come home from travel. And just, I won't eat for three days. Sometimes, two weeks I can go without food. It's not a big deal to me. Two weeks without food. Yeah. Okay. I might munch on a piece of celery or something, but that's not really nutrition. I will drink a lot. I'll drink a lot of low calorie, zero calorie drinks, a lot of tea, that kind of stuff. But I can go without food for two weeks. It feels great after the first three days. I'm over the hunger feeling. I can see on my monitor, which I've got one on here. CGM. The CGM. Yep. I can see the great impact it's had, having on my body. I can monitor it on my rings. I do blood tests, which is important. You don't want to just guess what's working, what isn't. But yeah, I know two weeks sounds like a lot. But it is a lot. It doesn't sound like a lot. It feels great. It is a lot. And I'm a regular guy. I'm not like some people that spend millions of dollars on their body and measure everything. I'm kind of lazy. I don't like being hungry. I like food. I like to snack. I like to stay up late. I'm a typical hedonist if you let me go. And actually up until a year ago, I actually hadn't fasted more than 24 hours. I just couldn't do it. This is painful, and I'm stressed. So if I'm stressed, I'm going to eat. But what I've learned over this past year is I can go beyond 24 hours. And once I'm over three days, something kicks in. Actually, we know molecularly there's something called chaperone mediated or tophered to your CMA, which is the deep cleanse of these misfolded and modified proteins that you want to get rid of for aging or a slowing aging. And after those three days, I start to feel amazing. My mind clears. I don't feel bloated at all. I don't even have to go to the toilet that often, except for all the tea. But you know what I mean? And yeah, I feel energized. And I'm measuring myself. So I'm making sure I'm not overdoing it. This is not for everybody. If you're skinny and you've got belly, any fat, or you're elderly, it's not for you. But for me, I gain weight and muscle pretty easily. I can fluctuate. And so I watch my weight come down. I've got a scale that measures my weight. It's-- I don't know if I can say the name or if it's forbidden. But I do like the withings scale, because-- Smart scale links to the phone. Yeah. We get your composition as well if you hold the handle. Yeah. And I've had one since 2013. So I've got all this data on my body weight and composition, which is awesome. And I'm trying to maintain that at the optimal level over these last 13 years. What are you-- This two weeks things blow in my mind. What are you running on after 10 days? Why is malnutrition? Are you supplementing with vitamins and stuff so that you don't get scurvy? Why are you dropping dead? I am. I'm glad you said that, Chris, because it's important to say, I'm a scientist about this. I'm not just willy-nilly giving up every-- To use salary and green tea, surviving for two weeks, just bro sizing it. Well, no, I'm not doing that. The reason I'm using my hands is I travel and at home, I have a little carry pack with vitamins, supplements, and medicines that I've been using, and know very well what I need every morning. It's a symphony of supplements and medicines, actually. I know what my body needs and know what works. So I do that. So that's not-- not anybody can do that. So it's really important if you do fast for long periods, make sure you're enough hydration, very important. We know that. But also, I'm making sure that I'm not deficient in any minerals or vitamins. And so I'm taking in things like vitamin D, vitamin C, as well, and some nutrients that I know I can become deficient in. What do you think is happening inside of your body after from day four until the day 14? What's going on? Well, we know, actually, not from measuring me, but we know from many years of study what happens to this human body. The first 24 hours, you're going to use up a lot of the sugar and then the glycogen in your liver. What I like to think is, my liver knows how to steady my glucose and give me the right amount of glucose far more than my mouth does. My liver's smarter than my eyes and my mouth. And anyone that's faster knows that your blood sugar, if you're eating this and you go, oh, energy, oh, brain fog, energy, brain fog. Oh, I'm sleepy in the afternoon. That's our normal life. If you're fasting, your liver just puts out just the right amount of ketones for your brain, or you can drink some ketone drinks, or it's making glucose, or both. Your brain loves ketones. And if you do it too long, you will start to lose muscle. So I'm working out more than I do normally to make sure I don't lose any weight. And so that scale will tell me if I'm losing lean mass, which I don't want to do. And I make sure that I don't lose it. - Is there not a concern to do with your gut? Is there not, does there not need to be transit through the digestive tract? I don't know what happens if nothing passes through your stomach for two weeks. - Yeah, well, I can tell you, your stool changes. - I imagine it does, it turns fucking invisible. - Yeah, right. - There's phantom poo as a stool. - The bunch of gas coming out. So yeah, that's what I meant. I'm not in the bathroom as often. It's actually much more productive, unless you're productive. - I do find it. do you find that the biggest obstacle to my productivity is the bathroom actually? Are you sure you're not tweeting the way down there? But yeah, your microbiome, I think, and this is not proven by any means, but I feel like just like your body, it helps to give your microbiome a shake up a bit of hormesis, which is a little bit of stress that's good for you. And I would love to do an experiment on myself as well, measured before, during and after, and see what happens to my microbiome. That's Laura and stuff like that. Well, I mean, I know that some of the proposed positive effects for GLPs include slowing mortality through the gut, which actually helps with things like SIBO or Candida or Hpilori, because this is why everybody, every burl lifter that's listening to this, you at some point in your life have glanced off the bottom of SIBO or maybe have it right now, because just the sheer volume of food that you're putting through yourself all the time, grazing, high protein, high starch, that's one of the proposed mechanisms, I think, that helps from GLPs. I don't know. That's what I was interested in, maybe creating this very, I was going to say sterile environment. It's not it's barren, this completely vacant environment for two weeks. I have no idea what that does. If you had overgrowth, does it kill it all, because it's not being fed, does it allow it to create castles and cathedrals and, you know, armor itself? Yeah. Yeah. Well, I don't know the answer to that. I do know that there's some really interesting things in bile that comes out more when you're fasted. One of the components is a type of colic acid, which is the black stuff that goes into microbiome and your microbiome converts that into a molecule that goes back into bloodstream and turns on a longevity gene that we've been working on. It actually binds to the protein and makes the protein more active. It's called CERT1. If anyone's read my book, they know what CERT1 is. CERT1 regulates the epigenome, slows down the changes to the software. And so long story short, it's at least plausible and there's a nature paper on this from another group that I reviewed. But when you're fasting, your microbiome is more actively converting bile into healthy molecules. As well as short-chain fatty acids, there's a lot of literature on that. And these molecules go into your body and they signal adversity. And you know that I like adversity. Adversity is good for your health. There's abundance and adversity mode that both good, but you don't want to stay in one or the other. You'll accelerate your aging and you'll die. So you want to cycle between adversity and abundance and your microbes help you get through that. What would you say, let's say that someone finds this quite seductive? What would be a good start? One day fast, a three day fast, and what should they do? What would be a rough protocol to follow without having to be a conductor of supplements? Well, if you're, if you've never fasted and you just wake up and you eat a normal breakfast, lunch, dinner, eat your obese or you exercise a lot because that's going to put on weight. But if you are willing to try, I would suggest skipping one meal and replacing it with a lot of liquids. So for me, I don't mind skipping breakfast. Not everybody wants to do that because they work out and they feel like they need some food. So you can instead, you can skip dinner, I would just have a very early dinner. What I was doing for many years, probably 30 years of my life, was trying not to eat anything until late lunch and you will initially feel hungry. This is the thing. Don't give up because it takes a few days for your body to get used to not having the food. It'll be screaming at your brain, I'm so hungry I'm going to die if I don't eat this bacon and eggs, but get through it and actually after two weeks it'll become really weird to eat food in the morning or at night, your body gets used to it, your brain gets used to it. But it does take a while and the cheat code is fill your stomach with lots of liquids. Not sugary drinks, not a lot of calories, zero if you can or just a little bit. I do have a little bit of calories in the morning because it's good with my supplements. But a lot of water, so a low calorie drink like this or water tea, black tea, coffee is very good. They're both good. Actually tea and coffee are both very good for you because they contain other molecules like polyphenols that again can activate these enzymes that protect us. Somewhere along the way low energy just gets accepted as a part of getting older. Turns out, there's a reason for that. As we age, our mitochondria, the parts of our cells that power us, become weaker and make less energy, which is why I'm such a huge fan of timeline. They've developed this that helps to clear out your damaged mitochondria, so your cells can actually renew themselves. Timeline is backed by over a decade of research and has more than 50 patents. And there's the number one recommended mitochondrial supplement on the planet. This isn't just theory. In clinical trials, people saw mitochondrial renewal increased by more than 40% in just 16 weeks, along with improvements in their overall energy. I've been using it for over two years since my doctor recommended it to me way before I partnered with Timeline and eat your heart out Martin Shkreli because they just dropped the price. And it now starts at $99. Best of all, there is a 30-day money-back guarantee plus free shipping in the US, plus they ship internationally. And right now, you can get that $99 price within additional 20% off by going to the link in the description below, or heading to timeline.com/modernwisdom using the code modernwisdom. A check out that's timeline.com/modernwisdom and modernwisdom. I'll check out, have we seen any data that shows calorie restriction increases lifespan in humans? I know that this exists in rodents. Yes. A study that was done was it macaques or something and that didn't actually work because it was a two-decade study. And the first version of the study, it turned out that they hadn't fed them the same diet and split it in half. They'd fed one of them a junk food diet and the other one and been given an healthy one. And they ran it back and it seemed like the data was mixed there. What's the evidence about calorie restriction for longevity in humans? Is there any? No. There's a lot of anecdotal and historical evidence that fasting is good for you. And there have been some short-term studies over a couple of years. There was the calorie study that showed that you could improve a lot of health biomarkers in humans over that time. That had lasting effects, including on the epigenome, but nobody's really done a prospective study with placebo, it's very hard to do that or even controls. So there's no proof, and I don't think anytime soon there'll be proof. But who wants to wait another hundred years till that happens? You can't. You've got to at least go based on the evidence. And in animals, it's incontrovertible that if you do it with nutrition, not just starving, it's very good for you. And that's why I do it. I would say with the monkey study, I know it very well because the two labs that disagreed about this, one is one of my best friends and the other one is my trainee. And they were. Oh, well, you're like Switzerland. Go on out. and did between the two of them. Yeah. I didn't really get involved, but I did bring them together and they came to the conclusion that yes, it did extend lifespan. It depended on the veterinary care and other environmental things. The University of Wisconsin where the other lab is, Rosalyn Anderson is the professor that I originally trained. What is it? 20 years ago. She runs the study now and her monkeys lived longer. And they also definitely incontrovertible evidence that they had less cancer and I think heart disease. But definitely overall disease burden in these monkeys was lower. And they lived slightly longer. But even if they didn't live longer, I would say still look at the data on the diseases. I mean, who wants to get cancer and heart disease in their 60s and 70s? Why would high calorie turnover increase your likelihood of cancer and heart disease? Well, there's a few different theories. The one that I like the best that's the simplest is that when your body is in a state of perceived adversity and running, building muscle lifting weights and hunger are signs of adversity. Also eating plants that are stressed is a sign to your body that your food might run out. This is put your body in adversity mode. And the sense that I mentioned earlier called CERT1, which protects the epigenome, it responds to hunger and exercise. There's a molecule called NAD that a lot of your listeners and viewers would know about. This enzyme responds to NAD levels. What long story short is when you're in adversity mode, your body switches from growth and reproduction into survival mode. At least if you do that for some of your day or some of your week, you'll get some protection against the ravages of aging, epigenetic changes, DNA damage, all of these things that we know contribute to aging. Do you think that there would be a marked difference between somebody who restricted their calories by 30% over a year, let's say, and somebody who restricted their calories by 30% with big breaks in food, calorie restriction versus calorie restriction through fasting. Do you think that those two people would have different kinds of outcomes? So are that one is eating more than the other? No. They're both eating the same amount of calories. Let's say that somebody has 100 calories an hour for 18 hours of the day, and another person has one meal that's 1,800 calories a day. There's a lot of evidence that eating within the time window is the one that's much healthier. The friend that I mentioned earlier, Rafael de Cabo down at the NIH here in the US, what he did, again in mice, but I think there's a lot of evidence that it would translate to humans. He gave mice, roughly the same amount of calories, but he gave it to them all day and they had to gobble it all down quickly. It didn't matter what they were eating. It was different amounts of protein, carbohydrate fat. He was hoping to find the optimal diet, but he found that the group that ate within that window lived substantially longer than the ones that ate continuously. I saw you quote-tweet something about protein being overhyped, the protein-maxing movement. What's your position on that? Protein is good. I'm not against protein at all. I eat a lot of protein myself, actually, mostly from plants for reasons that I'll get to. But this die hard, be a carnivore, forget about the green stuff is definitely not consistent with the science of longevity. It's consistent with the science of bodybuilding. It definitely works. Of course, as we know, it's a superior science of longevity. Well, as much as it doesn't look like it, I really like bodybuilding over other exercise. I'm just busy. I used to work out a lot. I love bodybuilding. Protein is essential for building muscle. No question. You can get a lot of protein from protein supplements and meat, where I think it's been overhyped is we know that plants are essential for providing polyphenols. And having a lack of branch chain amino acids specifically is also very good for health. A lot of data on that, especially in animals, but some in humans. So branch chain amino acids, some people listening will know what they are, valine, isolucine, these are three of the 20 amino acids that are found in more abundance in animals than in plants. And when you give animals a lot of these branch chain amino acids, they live shorter than if you give them less. And this has been shown in short-term studies in humans. If you're a strict protein that has a lot of branch chain amino acids in humans, they get better metabolically. But I'm not saying you can't eat meat or you can't eat protein. What I'm saying is just doing one or the other is not really the best way to live. I think the best way is to pulse it. So if you're working out, you want to build muscle, yeah, you can eat meat. I eat meat occasionally. It's not a problem. But you want to have a period of your life or let's say your day or your week where you're not eating meat or you're just not eating. And that puts your body at least part of the time in this adversity mode. Would you be doing both? Let's say that somebody is doing Omar or 16/8 or some sort of fasting protocol. Would you still be looking to pulse protein intake as well, separately to that? Yeah, yes. The answer is maybe go one day a week without protein as well. Well, without protein, I don't think you'll live. You need some protein, but you mean huge amounts of protein or you mean meat? I mean, like you're saying that there's time for you to focus on protein, and then there's time not to, you should be fasting. I'm wondering whether you should be fasting from protein from a micronutrient standpoint as well in your opinion. I don't think so. I don't try to fast from protein. I try to fast from a lot of calories. And I also try to fast from a lot of animal protein, which has these branch chaining amino acids. And we know the molecular mechanisms, there's mTOR, which anyone who follows longevity will know about this mTOR. And if you're eating a ton of meat every meal or every day, your mTOR is going to be active. And mTOR's role is to help cells divide, grow, build muscle. Great. That's what you want to do when you're young. You want to build muscle. You want to look good. You want to be strong. Even if you're older and you have sarcopenia, mTOR is good. But we know that animals that have active mTOR live shorter than those that have less active mTOR. So how do you get the benefits of both? Well, that's what I'm saying is have mTOR switched down, plant protein mainly. Don't eat a lot. MTOR will help you when it switched off. But you can rev it up when you want to build muscle or run a marathon or something like that. You don't always have to be in one state or the other. Okay. Talking about exercise, has your exercise philosophy changed? What is the best exercise protocol for longevity in your opinion? No. It hasn't changed a lot. I just keep seeing studies that say the same thing over and over again. And then people argue about the latest one. We know that the best health is accommodation of weightlifting. Muscle is good for hormones. It's good for not breaking bones when you get older. Balance is important. And then the other one is aerobic, VO2 max. We know VO2 max is correlated with very long life. And so you do need to lose your breath minimum three times a week, 10 minutes. It's rare that people talk about sex as a way to exercise. I see your eyes bulging. I'm just waiting to see where you're going to go. Well, I was looking at it at a tweet the other day at an X, whatever we call them now. And it was saying, Oh, I think I won't say who it was, but they said, Oh, you can lose your breath 10 times for 10 minutes, three times a week by doing XYZ. And I thought, no one ever mentioned sex. So if you have an active sex life, count that as part of your daily longevity routine or your weekly longevity routine. Okay. But also sufficiently vigorous sex can be if you can go for 10 minutes vigorously. That's a good start for longevity. There's sometimes restrictors for that that aren't simply cardiovascular, but go on. Well, you can supplement it with just running on a treadmill, going outside, rowing, sport, all of this stuff. Just as long as the way to know if you're exercising enough to build up your VO2 max is you shouldn't be able to carry out a conversation easily like this. You're panting. That's my judge. I need to do a lot more of it. These days I tend to do a lot of my exercise aerobically running to catch a plane. I admit that I'm not the perfect role model for exercise, but I do know what the science is. And that is the combination of the weights, the balance in the aerobics. What about zone two? You haven't mentioned low and slow. Well, if you can't do fast and quick and hit low and slow is fine. Walk, move, get up. I'm always walking around my office. I have a standing desk. I really sit down. So that kind of exercise is very good, certainly for balance, overall metabolism. So yeah, I try not to sit at all. I'm sitting now, but I really sit during the day. It's one of the things people find weird about me. They come to my office and I'm pacing. I'm twitching. I'm often chewing gum. That's not the same as zone two, though, right? No, no, no, you need to do a little bit more than that. What I like to do is a sport, tennis could get you there. I do a lot of gardening, so I'm carrying stuff, gardening is a sport. Yeah, that's my sport, actually. It's my big hobby. Interesting. Lifting a lot of heavy plants and building walls and hammering and drilling and all of that stuff. Yeah, a little bit kayaking is something that I like is good. I'm not out of breath, but I'm getting a good workout. Sleep and recovery and rest. What is the most up-to-date data saying around that from a longevity? It's still the same. You do need to watch your sleep. If you're not getting quality sleep or sleeping for that long, it's going to affect your metabolism. Figure out how much sleep your body needs at a minimum. You can do that using some of these rings. It's very good for that. Some people need eight hours. Some people need seven hours. Typically if you're younger, you need more. The good thing about getting older is you need less typically. But it's also about quality. I can get away with five hours sleep and my HIV is still in the 80s and 90s because I'm getting deep sleep. I'm not drinking caffeine late in the afternoon. I practice as best. I can relaxation, meditation, practices breathing. That gets me to sleep and into REM and deep sleep pretty quickly. I also take a supplement that my partner Serena makes. It's got L-thene and some other stuff that also I know from my own experiments gets me into deep sleep quickly. My efficiency is typically according to these rings in the 90s, 90% sometimes close to 100. Then I can get away with less, which is nice because I travel a lot. I think that's the big learning that everybody who starts using a wearable takes away from it, which is your sleeping way less than you think you are. I was in bed for eight hours. You thought you went to bed 11, but it was actually 11.30 and you were reading or watching TV until nearly 12. Then your actual efficiency was maybe 85% so that seven hours has turned into 5.45 or six or something. It's stark. I've got maybe 2,000 nights on boot tracked over the years. You're just always sleeping less than you think you are. If you don't have money to buy a wearable, just the rule is you're sleeping less than you think you are. That's it. I agree. Especially if you're eating late, drinking coffee or tea late or matcha, caffeine and alcohol are big ones for a bad sleep, not just stress. Having a hot room or too many blankets is another mistake make that a lot of people make, you can get those beds that are cool. 8-5. sleep is anyone that's not using an H sleep, it's medieval. I understand they're expensive, but there's no one that I've got to do. Yeah, they're a partner on the show or whatever, but like this has got nothing to do with it. Every single person that I've got to try it can't believe that what life was like before they had a cool. And there's other cheaper versions out there, I'm sure H sleeps the best, but there's other ones that you can get. Trying to cool your bed from outside of your bed when the job of your bed is to keep the temperature in the bed the same is kind of a little bit like fighting against the tide. Yeah, exactly. And you should wake up every morning feeling totally rested, excited about the day. If you're waking up and like, oh, I need a coffee, oh, I need a shower, you're probably not getting the sleep that you need. You mentioned stress as well as kind of the fourth pillar when it comes to lifestyle. What is that? Look, how do you come to think about stress as a longevity doctor? Yeah, well, you can measure cortisol, for example, or DHE, cortisol levels. We're all stressed. The old days of sitting around a campfire are not really there anymore. We're driving to work. We're worried about income. And so what we want to do is learn to deal with the daily stress. The world is changing faster than ever. So what I've learned personally is really not to let worries of life get me down. I try not to focus on them. I have a happy place, which is an orchard on Cape Cod. And my mind, when it's stressing out and I feel my body tense up, I take myself there, I breathe. I'm amongst the trees. If it gets really bad, I go there physically and do some work. But yeah, it's all about learning not to ruminate. And a lot of us, a types, I'm sure you in your success or like that. What did I do wrong? I could do that better. I'm worried about tomorrow. I'm worried about next week. I'm worried about 10 years. Don't do that. It took me 50 years of my life to figure out, don't do that and how not to do that. How do you stop worrying? You have to train yourself. It's like, don't be an idiot. Stop thinking about it. It's not going to kill you if you distract yourself with something else. Thinking something is a real issue for modern life. So I don't do that anymore. If I find myself overthinking, I'll just say, I'll think about it later, put it off to the side. And I used to be the kind of guy that I had to text back immediately and email back immediately. Put it aside, I'll get to it. I think a lot of people are driven by the overthinking intrusions that they just can't get their brain to focus on what's in front of them. There's always this concern. There's always this situation that could be a little bit worse, this thing that could make life a little bit harder that's coming down next. And yeah, you're kind of being puppeted by these ghosts of the future that haven't yet come about. Yeah, that's the thing. What you realize when you get to my age, I'm now 57, is that it's never as bad as you think. What I do now is I depend on myself. I know that these big problems in my life and I've had big ones, deaths and issues. You get through it, you trust yourself. You know, maybe when you're a teenager and you're 20s, you don't know that you can get through these things. I'm at a age where I know I'm not going to die. I'm going to get through it. It's going to be okay. If I have a problem, I'll solve it. The sooner you can realize that, that you are capable of anything if you put your mind to it, then you shouldn't stress about problems that come up. Tell me if this sounds familiar. You train regularly, you eat reasonably well, you feel fine, but you're just kind of going off vibes. Most people have absolutely no idea what's going on inside their body and that is why I partner with function. Function gives you access to more than 160 advanced lab tests spanning hormones, heart health, kidney function, and even detects early signals linked to more than 50 types of cancer. To put that in perspective, your typical annual physical might test 20 markers. It runs over 160. It's huge. Best of all, you test twice a year and everything lives inside of a simple dashboard. So you track trends over time, make sure you're moving in the right direction, and this level of testing would usually cost thousands, but with function, it is $365 per year, just $1 a day to actually know what's happening inside of your body. Right now, we can get $25 offering it down to $340. Get the exact same blood panels that I use and save $25 by going to the link in the description below or heading to functionhealth.com/monum wisdom. That's functionhealth.com/monum wisdom. Okay, let's talk about your current drugs stack. What are you taking? How's your daily stack changed versus what you were doing when you wrote the book? It hasn't changed. That's the amazing thing. I thought I'd have to change things to being on the science, but the science has held up. So in the morning, and if you go to page, what is it? 304 of lifespan. It's still there, and I still do that. Rizvertral. It's been back and forth controversial. It's not controversial in scientific circles. There's a few naysayers, but they make it living out of it. Rizvertral is from plants that are stressed, and they activate certain ones, this resetter and slower of the epigenome noise. So I've been taking about a teaspoon, call it a gram of Rizvertral every morning, almost every morning for the last two, probably 20 years, doing all right. It seems to help in clinical trials. It's been tested in a number of clinical trials. I mix it with it either a little bit of olive oil. That's my calories, or Greek yogurt or vegan yogurt, and it's been good to me. I also take that with NMN, which is an NAD supplement. It's a precursor. We studied both in my lab, and we just resubmitted a paper. This is something I can reveal. We just resubmitted a paper to be published. That showed that NMN is very good for the health of old mice, and can extend the lifespan of mice, particularly females, and so that will come out probably resubmitted. Yeah. We had reviewers, comments, criticisms spent another year working on it to please them and send it back. We'll see what they say. What was the controversies? I know since the last time we spoke, there's been some fuel around Rizvertral, some more fuel around NAD, maybe NMN as well. Can you explain what happened? Yeah, sure. These are all typhoons and a teacup or whatever it is. Constructuring your drinks. Very good. That's all I needed. So let's start with Rizvertral. I try not to bore everybody. CERT1 is an enzyme. I'll use my hands. It's an enzyme that carries out reactions that stabilizes the epigenome, so it doesn't decay, so think of it as stopping the corruption. The software, more CERT1 is better. So there are two ways to activate CERT1 with a pill rather than exercise and dieting. If you do all of them, I think it's the best. So you can either take Rizvertral and that we showed in 2003, a long time ago, I'm old, activates CERT1 directly. So the enzyme is removing chemicals from the epigenome and making it stable, and it can do it slowly. You know what a Pac-Man is? You're old enough. So it's chewing away the chemicals stabilizing things faster, the better. Rizvertral binds physically to the enzyme and now makes it chomp faster. The controversy that came up was that Pfizer or a team at Pfizer, not the whole company, just a group in the company, put out a paper in 2010 that said Rizvertral doesn't do this. It must be an artifact, it's doing something else that makes it look like this. So we then spent three years testing that and found exactly how it works to the atomic level. We could even block it by changing an amino acid in this protein. And we actually have a study now that we've made a mouse that has this block and Rizvertral doesn't make the mouse healthier anymore, it doesn't live longer. So that's as good as evidence that you could get that we were right in the first place and Pfizer was wrong. And we've put out papers since and others have shown that we were right. So no controversy going ahead with Pfizer's no small task. It was brutal. That was one of the hardest things in my life because I remember trying to defend myself in public. It was on NBC. And I said, I'm not sure what Pfizer is doing, but our chemicals don't kill mice and they activate the enzyme. And the comments were brutal. Sinclair thinks he's better than Pfizer. Pfizer knows what they're doing. I will say that I don't have ill will towards those scientists because it's the job of scientists to challenge theories. What I do have a problem with is the the people who still say it's wrong and are trying, you know, just to get at me there. What's the remnant if you've put something out which pushes back against Pfizer? What is the remnant argument? There isn't one. The problem is that what I've gotten to see in my career over 30 years is the media loves the negative story, but the redemption story isn't as popular. So it's never come out in these journals like Nature. They put out the negative story, but they never did the Oh, we were that was wrong. So it's just a matter of reporting. But in scientific circles, everyone's read our science paper from 2013. And it's not debate. That's put into right that the evidence is put to rest in your opinion. Yeah. Yeah. It's at the atomic level. Unless you want to complain about atomic you know, we're done here. - Okay, and what happened with NAD, NAD? - So yeah, let's bring everyone up to speed on what NAD is. So CERT1 also can be activated by giving it fuel, which is NAD, CERT1 chomps with NAD. And in fact, this is not often known. The chemical that it takes off the epigenome structures is donated to NAD. So without NAD, you can't take the chemicals off. And more levels of NAD make it work faster and better. And if you give it to cells, you see more stable and healthier cells. There was dogma that NAD levels went down with aging and that boosting it back up was healthy. So the second part is true. We have shown in cells, in animals, and even in humans for the last, and by we, I'm in the field, not just my lab, that raising NAD levels above normal baseline is very good for humans. I can give you examples. Shelley Basin, you could look up in PubMed. He's got a couple of really good papers giving NMN, which is the precursor to NAD to people that are either obese or pre-diabetes or even super fit ones. Maybe the super fit isn't published yet, but he's done the work and reported about it. You see improvements from lipids, whole bunch of lipids, cholesterol, blood pressure, body weight. So raising NAD, I think most people would say that it's good for humans and animals. And again, we're going to publish that it's good for longevity too. Where the debate that came up, I think you're talking about the one that was maybe a few months ago. Somebody showed that human blood levels in white blood cells, the white blood cells don't have less NADs you get older. So some people who love to make a living of being naysayers, especially towards my career, jumped on that and said the whole theory is wrong. If white blood cell NAD levels don't go down with aging, then the whole theory must be incorrect. Which is, as you can tell, is complete BS. In fact, we've known for probably a decade that that was true. It doesn't affect the theory. We know that raising NAD levels in humans either by exercise or by supplementation is good for you. So it was crazy to say the whole theory fell apart. It was just a way to get clicks, I think. What's the status? I'd looked at something to do with it. It was a pharmaceutical, then it was a supplement. And now I don't know what the level of access is with NAD and stuff at the moment. What's that classified? Or just a final thought. A really good study that showed that people who have lower levels of NAD and their muscle, I think it was not as metabolically active as those that have higher levels. Or they had metabolic syndrome. Anyway, we could check it out. But there is some good correlations between NAD levels and age-related conditions. Want to be accurate. All right, so the FDA thing. Basically, it was that there's a rule in the US that if any molecule, whether it's natural or synthetic, goes into a human clinical trial, before it's on the market, people can't put it on the market. Because then it negates the reason to do a clinical trial. And we need clinical trials to know if things work. Makes sense. The law makes sense where things got crazy was a company that I started called Metro Biotech. Started a clinical trial with NMN. And a little later, people started putting NMN on the market. And I've always said publicly, you can read it. Fine, let's do both. Let's do the clinical trials, make a drug. It's going to be pure, it's going to be tested. And there'll be supplements that are less rigorously produced for people that are not sick. But for the sick ones who have diabetes or need a drug, we'll have that. Happy world. The legal team at Metro Biotech made a decision without my approval, actually, with my disapproval, to write a letter to the FDA pointing out that there was this law that they shouldn't have simultaneously sales and clinical trials. I objected. The FDA initially said you shouldn't be selling NMN on the market in the US, according to that law, though they didn't enforce it. And then it was recently reversed. So now it is enforced? No, I mean, the opposite. The FDA, I believe, says it's okay to have NMN on sale. Oh, interesting. Okay. There was a court case that I think resolved that. Are you still taking the baby aspirin? Yeah. I am. That's controversial, too. One baby aspirin a day? Yeah. The 81 milligrams, though, 81 is only because a trial did 81. It's not magical. But yeah, you could take 100 probably. But talk to your doctor. Do you want to talk about aspirin in detail? Sure. The reason for the controversy is if you dig into it. And, you know, I do this because it's my living. Most people don't have time. The American Medical Association weighed the risk of having stomach bleeding and other complications versus lowering the amount of risk of cardiovascular events and came to the conclusion that looking across everybody, it doesn't make sense. But I'm totally against the word everybody when it comes to health. Everybody's different. So I believe in precision medicine. And there's a group of people, for example, that it does make sense to take baby aspirin. It's been showing that there can be benefits. And it's those people, just as an example, who have high levels of lipoprotein A or LB, little A. I'm one of them. So I continue to take baby aspirin. But these are decisions to make with your physician. What else? I can't work out whether we call breast-vera-trolis supplement or a drug or a pharmaceutical. I'm sure you can get it in pharma grade. But what else from the not foods consumption stack? Because aspirin would definitely be in the meds category, I suppose. What have we missed off? Well, there's a whole website devoted to what people think I take every morning. Okay. Set the record straight. What is it you're taking? Well, that will, I'll have to come back for another show or people can listen to my podcast. Yes. Because it's a whole box of things. And I'm not taking them all the same day. But I still like apple-apoeic acid for mitochondrial health. So I've been taking that for over a decade now. I did a PhD on it, so I know a little bit about its benefits. But that was a long time ago. Let's see, co-cutane, of course, because I'm actually on a statin. I might switch to a PCSK9 inhibitor, because it's more effective. But my family is very high-class. I'm on a repathor. Great. You like it? I've actually stopped taking repathor, because I want to see if it's causing some brain fog. Oh. That is sometimes associated to anecdotal. But I noticed, ApoB went through the floor. Fucking brilliant, brought everything back in line. Isn't that lovely? Brain stopped working quite in the way that I wanted it to. Okay. Well, let's see what happens if I take a little bit of a break and let's see if brain comes back in line with where I want. But I've found repathor, largely, it's every, I've got the every two weeks one rather than the monthly. And that's been good. I've also been taking telmasartin as well, because I've got, I didn't realize this until I guess I've done a lot of health discovery since the last time that we sat down. I have every polymorphism under the sun for somebody that's going to have high cholesterol and high blood pressure. It's just a really perfect suite of hyper absorber, hyper retainer, all of the dispositions that you want. Are you on Zedia? No. What's that? That's the common name. I thought I'd use it. It is the drug that blocks uptake of cholesterol. So the combination of a statin and the Zedia has been shown to be very effective at low and cholesterol. The supplement industry is full of products making claims that they can't back, which is why I'm such a massive fan of mementas. Their co-founder Jeff Bae has played in the NFL and saw firsthand just how wildly the quality of supplements can vary. So he built mementas around a higher standard. 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I did carnivore toward the back end of 2024, meat and fruit, technically, for six, nine months or so when I was recovering from living in a house with toxic mold. It was really brutal, but I actually felt phenomenal, looked great, shredded, jacked in the gym, energy was good. Little on edge, like a little adrenaline all the time, but that's maybe to be expected without any starch or carbs to sort of really bring you into land. And I managed to get my cholesterol up into the 400s. 400s. - Which, four hundred? - Yep, yeah, it was really impressive. It was kind of like a person holding briefly, and then had creamy blood. - And then brought it back down. But it's kind of what I've come to you right to say that everybody is different. Everybody has a different system. And the fascinating thing when you do these sorts of playing around with ex-self experimentation and intervention is you find out there's something that can make you feel amazing. Make you look amazing. Like in all of the subjective metrics that I care about, shit's going great. Except for the one that might kill me pretty quick. And then I went and did a clearly scan, which is fucking unbelievable technology, by the way, basically this special type of contrast scan is able to look inside of the arteries of your heart and look at plaque buildup without having to do anything in base it, it's magic. And I had a small, very small, but mild amount of plaque progression. Okay, I need to put the kibosh on this, regardless of how jacked and alert I feel, I need to eat a much more sort of Mediterranean low fat protein diet. - Yeah, and I know it's not proven, but I do like the idea of plaque reversal. So there's two ways that we know of that might do it. One is reducing your LDL so low that it reverses. So the repath of that kind of drug, there's an oral PCSK-9 inhibitor just come on, has come on the market, which I've got a prescription for I'll try it out. That's one way. And then the second one was based on a study that had a thousand people in China. I know it's not the perfect study, but to me it looks like it might be true. And given that this substance is so safe, the downside is cost me a few bucks. - Nato kinase. Do you know about Nato kinase? - No, what's that? - So do you know what Nato is? - Natural? - No, you're lucky. Anyone who's been to Japan probably has seen at breakfast in the hotels, they serve this goopy bean sticky substance that if you lift it up it looks like cobwebs. And it smells like vomit. So Serena eats this stuff. I don't know how she does it. I have to hold my nose. That stuff, it's bacillus subtlest and smother bacteria eating soybeans. They found that there's an enzyme in that stuff that if you swallow it, it can remove, but at least it looks like it can remove plaque. Hence, Nato kinase. Kinase is the enzyme, Nato is the food. And so I swallow, depending on the day, about 10,000 units of this stuff every morning. And I'm getting some sort of capsule. I guess just a capsule you swallow it in the morning. And I'm gonna measure it. I typically do an ultrasound on my carotid every year. Similar, it's like the clearly, it's just on your neck. And you can actually do your intermediate thickness, which is important. Tell your doctor if they do that, tell me my IMT. And that is a number that will tell you very similarly how you're doing cardiovascular for your whole body. And I'm gonna see if Nato kinase makes a difference. - Fascinating. What's all this hyper undirectile dysfunction medication? - That's a lead in question. Well, yes, it's recently come into social media because it was found that these ED drugs are also good for some types of cancer and can change the immune system so that it goes from protecting the cancer to killing it. And I tweeted out what's not to love and millions of people saw that. But I'm serious. I take what is it? See Alice is the common name to Dalette Phil. Every morning, there's some aloe dose. It's just a little bit. And I do that because in 2012 we published a paper that showed that one of the most pernicious causes of aging is low blood flow. And then we could reverse that with NMN through CERT1, more blood flow. And it's really underappreciated how much a lack of blood flow leads to diseases. Especially your muscles and your brain. And so I take this low dose in the hopes and expectation that I will, if I get dementia, it will be a decade later. And now add on that cancer killing. It's an amazing drug. And it was actually not even developed initially for these. - It was an angina medication. - Exactly. Do you know the story of why they realized it had that side effect? Was it pulmonary? - No, I bet I didn't think that. - When they were doing the trial, typically you do a med trial and patients come back into the lab and you ask them to give the drugs back and nobody has an issue. But none of the guys wanted to give the drugs back anymore. And the nurse is noticed that the patients when they were doing their interviews were sitting cross-legged. And they had this strange contorting of the posture to try and hide the fact that they all had heart ons. And they said, hey, we need the angina thing when I was a share about it, but we've done some wonderful stuff to the penis. - Well, I can say taking a low dose, the good news is it doesn't make your penis get erect without warning. That isn't a problem. But the low dose really, let's put it this way, I haven't had any downsides yet. - Fantastic. There's one other thing, Chris, I want to say, which before I forget in my old age and my lack of blood flow is, so there's a study in my at least that hints that lack of blood flow to hair follicles is a reason that you lose hair. And so my hope scientifically is that continuing to get blood flow in my hair follicles will keep my hair. - More heart ons less balding, that's the equation. - I don't know which one I'd choose if I had one, but. - That's true. I guess a lot of guys don't have that choice. Human had said something to do with the perfusion of the prostate as well. The opening up blood flow is, especially given how close you are to ground zero, might be like a useful side of it. I don't know, man, I said, my favorite conspiracy theory about this. I hope that it's working. I hope that it's a pretty much all gains intervention that everybody can use. But my favorite conspiracy theory about why a reptile dysfunction medication is being pushed so hard is that it reduces any of the stigma of any one guy having to take it. So that darling, I've got to take it. It's important for my hair. Dr. Davidson Clare told me that it would stop me from going bald. And also, you know, a great grandma she had Alzheimer's is very important for my neurodegeneration. You don't want the prostate. You know, granddad, he had the prostate. Thanks. So the ED, you don't need to worry about that. It's normalizing. - There's a lot. I think you're 100% right. And I'm sure there had been some wives, like, honey, why are you eating 10 of them? So it's just-- - Yeah, yeah. What about omega-3s? You know, omega-3s commonly touted is something that's very important for people's longevity. Why do you come into land on omega-3 levels and supplementation? - I take an omega-3. The data looks really pretty good that if you have some of that, it's enter inflammatory. Whether or not it totally prevents heart disease, it's controversial now. But-- - Have you got a brand that you prefer? - Yeah, but I won't say it. - Okay, I'll tell you what, I use Nordic Naturals 2X at the best. - I do like them. - Yep. - Their products are really pure and distilled. You want to avoid the cadmium and lead products. - The ones that have heavy metals. - Okay, so I remember this. My mom would tell me this 25 years ago when I was a kid, and she would be taking-- there would always be this line of low quality cod liver oil back in the day. Low quality omega-3 supplements aren't really that good for you. So this is like, you know, mythological fucking ancient wisdom. - It really is. And actually while we're on the topic of contamination, I and other labs have measured supplements and they're often contaminated with things. And I even got sucked into a lawsuit because I said I tested this product on it or this type of product and it had contamination. But I do want to say at the risk of some litigious activity against me that NMN and these NAD precursors can have contaminants in them. Now I don't sell, I don't market anything, I don't get any money despite people using my name and even video across the internet. So I have nothing to gain or really lose by this while I've got a lot to lose. But nothing to gain. NMN can have things like, well, first of all, I think the study that was published, it's worth looking at by Andrea Meyer. She's out of Singapore. She found that a lot of the NMN supplements didn't have NMN in it. And if they did, it was a lower amount. And we found in my lab, which I don't think is in Andrea's paper, is that there is endotoxin in NMN, bulk and supplements. Endotoxin comes from bacteria causes inflammation. It's part of the purification process, but they don't get rid of it. And we found out the hard way we were feeding it to mice to make them look longer, which is not gonna work if it's contaminated. - Again, so even the NMN that you were using in your lab that you thought was pure, was so contaminated that it was infecting the study participants. - 100%. - Wow. - So we've had to really work hard with manufacturers to get it really pure. How hard do people need to work? If somebody's taking an NMN supplement now, is there anywhere that a normal person can go that's not going to risk being contaminated? Well, if I ever mention a brand, it's going to be, it'll block the internet might, I'd bring it down, but I will say that to help the viewers, the listeners of this show, I would go for a company that has a strong reputation, that provides the analytics. So sometimes they give the spec sheet and you can see the purity. And some companies, they've got such a big reputation, they're not going to risk adulterating it or putting something else in it or giving you less. GMP is important always, any supplement should be good manufacturer and practices, USB label, look for those badges of purity. And if your company that you like doesn't share the analytics online, you can write to them and say, can you please share that badge? Because it's not cheap. They're not cheap interventions for people. And if you're spending a lot of money on something, you want to make sure that it's actually, the worst thing is I'm taking this thing that I think is going to make me more healthy and it's actually making me sick. That's the real problem. And so what, and I'm going to do a shameless plug if that's okay. I'm launching a community, a website community, for us to figure this stuff out together. I'll be testing products. We'll learn what works together. And I hope that it becomes the world's largest longevity community. What does the community build around? What is it? Yeah, it's called lifespan.com. So my show is lifespan. This is the website version. My goal ultimately is to fix healthcare across the planet. We've done a top-down government, big industry, HMO. We know that doesn't work. The US especially is spending close to 20% of GDP on the healthcare and got some of the worst healthcare. So we've got to do something. So grassroots movement, lifespan.com will be a community that comes together to learn what works, what doesn't. And eventually, what I want to take this is that we change how healthcare is done. And with AI, with knowledge, with, we're also funding medical research and testing of brands. So we know what's pure and we'll find new medicines together. I want to share in the profits of that with all of the members. So that's being launched soon. That's cool. It's probably launched by now. There's for members so that there's an unpaid version. You can do show notes and you can see some stuff. But if you pay to $8 a month, we've pulled together something really interesting. We've got this community that we've built. But also there's information that will basically complement what we've been talking about today. There's a magazine. World's first magazine written, well written, by people who are doing the research. So you don't have to rely on some newspaper or reporter who doesn't know anything who also wants clickbait. I actually brought a copy of this magazine. I had it printed in hard copy just for you. Oh, let's get it. I want to see. You haven't seen it. This is been hidden here. This is lifespan magazine. First, one I've given out to anyone. And this is a gorgeous magazine that every member gets online. What if aging isn't damaged, but lost information, a radical idea now entering human trials? That's the paper from Nature that I thought I'd give you as well in 2020 that changed everything. This is so cool. Thank you. You have a look inside. I'm so proud of how it looks now. This is going to be coming out every month and it's got about 100 pages of the real science, the real stories of what it's like and what we're learning before it even comes out in journals and in the media. Oh, this is cool. Inside is very beautifully put together. Beyond your birthday, Steve Horvath on the science of epigenetic aging and a Steve Horvath. Yes, Steve discovered the epigenetic. Can a simple multivitamin mineral supplements slow down aging? This is awesome. Congratulations. Thank you. I'm very proud of the team. It's a small but mighty team that we really we're really driven by mission. We want to change the world and we want everyone to join us in it. Unreal. Other interventions, other stuff that's happened. Since we first sat down, the world of longevity, biohacking has really sort of, it's not exploded. I think it's become more sophisticated. You may say otherwise. The evidence may say otherwise, but at least from the self-experimentation, 2017, 2019, it was a lot of the biohackers handbook. It was Ben Greenfield's friend of the show sticking ultrasound things on his penis to see if he can improve his erection quality and his orgasm length and stuff. Then it seems like it's really come on database, a lot more evidence-based crowd stepping into this. Well, thank you to you. For example, guys like you are bringing scientists like me and people who know what they're talking about, so that people can hear it from the horse's mouth. Whereas before it was just somebody hyping and selling stuff, which you couldn't trust. It's true. I mean, what's been interesting has been to see, at least in Greenfield's case, how right he was about tons of stuff super early on. I didn't mean to imply Ben was one of those people. But there's so many, even a teamo arena was it that wrote the biohackers handbook? It's his coffee table book. I've still got my house in Newcastle. And I look at some of that and it's the same as the bodybuilder thing. So many bodybuilders stumbled onto a particular way to look at health or dieting or whatever, that a decade later, science then comes back around and says, "Hey, that's the way." But then also there are a lot of people that throw shit at the wall and much of it doesn't stick. One of the most popular interventions that people are talking about, contrast therapy, sauna and ice baths. What does the evidence say around cold and heat exposure for longevity? Increasingly, we're learning. In 2019, when you and I first met, those very little evidence, actually. And you're right, biohacking was something that was looked down upon, especially by doctors, and the public didn't know what was going on. Then came the pandemic and most people saw the mortality and it's like, "What are we going to do?" And it's amazing to see what's happened since that it's become mainstream and even doctors have had to learn about this because their patients are coming to them with more knowledge than they have, especially with AI now. But we are in a world now where the individual can know more about a certain topic than their own physician, which is incredible. That does include sauna and cold baths. When we met 2019, there was a little bit of data and so on as nothing on cold baths, except a mouse dunked in the cold. Now there's much better evidence. I put it in my book life span because I was told by the editor that that would be interesting. But I was hesitant because there was such little data on so on as and nothing on ice baths, really. That's different now. I can now say as a scientist, scouts on her. I was a scout. I forget how we do it. That definitely sauna, there's a lot of evidence. Mostly Nordic men have been studied, less women. But if you do regular what they call sauna bathing in Finland a few times a week, your rate of heart disease can be much less than and that is reproducible. So that I think sauna is a great. I try to do some of that myself as hot as I can bear. Ice baths contrast, it makes sense scientifically, hasn't really been studied. But cold therapy, we do know it can activate brown fat, which is very good. What does that mean? Well, so we actually, going back in history 30 years ago, we didn't know that we adults, humans had brown fat. Babies had brown fat. It's a highly metabolically active type of fat in babies that keeps them warm because they can't shiver initially. And then using pet scanning, people at Harvard, some friends of mine discovered that adults can have brown fat on their own bodies as adults, often they're in the back. You can get it more brown fat by by doing cold belt, cold plungers and being cold. Do you want more brown fat? Yes. I was going to say the brown fats full of mitochondria, which are healthy. These brown fat seems to secrete factors that are good for health. But yes, people that have more brown fat tend to have better metabolism in general, and they also burn more energy, which is good in today's world where there's too much food around. So yeah, in general, yes, brown fat is considered very healthy. But the older you get, the harder it is to make and convert from white to brown or beige. And so my view on that is, and that's true for my, so I'm not sure it's true for people, but let's say it is, I still believe that the earlier you start to build up your brown fat reserves, the better. Because by the time you're in your 80s, it's hard. Cold exposure is a good way to do that. Exactly. Right. I don't know if it's true, but I like to experiment with sleeping a little cooler. And as I wrote and have said a few times, turn down the temperature. Don't sleep with a lot of blankets. We've already talked about eight sleep beds. That is a way probably to burn more heat, more energy, but it might help If you're feeling cold during the night build up brown fat That is a might you will get more brown fat if you Cold plunge and do those kind of things roll around in the the snow It is controversial though. I did see a little bit of pushback against Wim off and what he was saying. It may not be as spectacular as what he's claiming the evidence for heat seems to definitely be stronger than the evidence for cold Like I agree 10 to 1 20 to 1. That's what I'm saying. Yeah It's strange because the immediacy of the reward if anyone's had a cold shower or used to cold plunge you feel really as long as you stay in for a little bit You feel so good afterward but I I'm I like to do it. It's fun or whatever But I would probably take a sauna 20 times overtaking a cold plunge If I'm gonna try and do something for my health. I'm the same. I do a hot every every day including a steam shower But I called plan probably once every two weeks at best by by turning on the cold tap. What you make of Brian Johnson's approach to longevity Well, it's totally different Putting the two of our side-by-side some people do it's it's not the same animal I'm doing science. I'm doing the research and figuring out the molecular mechanisms He's a compliment to that. He is self-experimenting. It's not a clinical trial. Obviously he will admit that but where I think Brian shines Is in a couple of areas. He's very courageous. I like that. He stuck his neck out. I have a lot of admiration for those people who are brave that way He's also been helpful bringing a spotlight to the field of longevity And I remember a lot of my colleagues my high-brow colleagues in longevity Really said he's the worst thing that's that's happened to us to this field. He brings a bad name to longevity But I disagree. I think that he that we as a field of scientists Had a marketing problem as much as we talked about longevity. It wasn't getting through up until 2020 almost nobody had used this word even Brian came along I came along definitely Brian got a lot of attention and I think it's been helpful to Wake people up from They're stupid not everybody but a lot of people just live their lives and eat whatever they want Do a little bit of exercise Brian said we can be much better a bit about this we can Science the heck out of this and I love that approach and so I think it's complimentary. I'm saying Let's do real science clinical trials molecular but also with an end of one Doing pre-treatment post-treatment see what happens under doctor supervision. We can learn some things too Yeah, I I think Brian deserves a lot of credit for for that for bringing attention You've got it. You've got a highly unsexy field. I'm not saying Brian Johnson sexiest guy in the planet But he's definitely made an existingly unsexy field at least a little bit more sexy What knowing what you know about his approach to? The fundamentals for longevity. Have you got any Smeltest or sort of lick your finger to work out where the wind is coming from or you think I might really be on to something there So something that he might be out ahead of where the the data or the research or the sciences at the moment Not really I don't pay as much attention to him as I'd probably Surehood or could I do look at some of the The blood work that he posts and there's a particular test That's called the Dunedin pace of aging, which is a measurement of your epigenine. Oh, I'm changing So we Steve in the magazine Steve Horvath discovered the epigenetic clock for those of you who don't know what that is It's chemicals on the DNA that change with time. These are like the scratches on the CD or the software corruption You can measure that. You can do it before and After or you take it every you know three months or every year and Brian has published publicly his results and you can determine what is representative of your pace of aging and His was I recall something like point four something this and one would be you're aging one year for every year Yeah, and you know if you're two the you're doubling your rate of aging. So you're gonna die early According to that. That's one of the lowest Paces of aging I've ever seen for human. So that's pretty impressive if that's maintained He could live decades longer than the average he's supposed to Then he would if he didn't take care of himself. Is that Taking into account talamias or no with that Dunedin pace of aging. No, it's not I don't believe so. It's I Just are looking at the what's called DNA methylation pattern on the DNA What do you think are the biggest wastes of money that people spend on longevity? Oh well The overdosing of vitamins particularly B vitamins I think that if you're on a vegan diet. Yeah, you should make sure you're not deficient in any B vitamins Generally if you're taking a lot of multi What do you call it multi vitamins? It's excessive and it can actually be toxic if you have too much so vitamin C Can be pro-oxidation not antioxidant if you take a lot continuously So overall, I'm not I'm not for multi vitamins. I Do believe you should measure your vitamin In your blood and if you're deficient, you should make sure you're not deficient But overdosing on vitamins, especially B. You know, you could do IV some people do that I think yeah, you'll get a short term hit, but I Nibble on my B vitamins. I don't take the whole thing. I tried again the self-experimentation over the last couple of years recovering from this this mold complex illness stuff has been interesting to say the least and The start of last year One of the potential culprits for why I was feeling so shitty was methylation So did a bunch of genetic testing came back up got four different polymorphisms that make me suck at B vitamins like one in the blood one in the brain one in the methylation and one in the summing else one of the potential put forwards Explanations was while your meme calicular volume your mcv is high It's like just like 101 or whatever, which is just above the upper range. Oh, well, maybe this is something to do with bees I was like, okay, well, I'll try some intramuscular methylated B12 Like 500 micrograms. So you tiny tiny tiny little that it's almost like go to put a huge needle in your leg to put this Teeny tiny amount of B vitamins in I didn't realize that you can get something if you push it too far called B12 induced confusion So you can actually just make yourself confused and your brain gets very slippery given that this was the thing that was trying to push back Against what I'm saying is I know what happens when you push B vitamins too far And I actually did that the week There's the biggest week of the show last year where I had Rogan I was on Rogan on the Thursday and then recorded an evolved rave count on the Saturday and I went into it going I've like Poison myself with fucking B vitamins and now I can't think straight. It was fine. It was it all ended up being great in any case But yeah, okay, so I'm spending too much money on Vitamin's multi vitamins is one of the biggest wastes. What else? Well at the risk of being sued I would say that's a big cue. I'm not sure about Again, I'm not saying it's wrong. I'm just not sure about certain laser therapy Serena my partner loves shooting lasers at her body, but I have a skin care Internal as well. How do you shoot laser internally? Well, which which hold is it going? Yeah, well it shines on your skin back and forth So I don't know if that is doing anything. I'd like to see some data on that is that like red light stuff It's red light, but it's different colors and wavelengths. Oh, yes. Yeah, I've seen those things There's huge big panels that people can stand in front of well. The red light is not crazy So certain infrared. I've got near infrared panels. I have that actually I'd shine that in the shower sometimes Okay, and that the science is coming around to confirming some benefits there so that I think that's fine and the red light Soreners, I'm gonna get one and see how that goes about the yellow lights and the others Yeah, these are the things it looks like it's fourth of July in in the house, but I'm not sure about that one But you know, you've got to be careful what you say is BS now turns out to be true This is where the biohackers get it right to this is where the biohackers get it. Yeah, even peptides You know now we're seeing a lot of them are actually really helpful talk to me about jail piece because you know, this has been this wouldn't have even been a discussion Right three letters that I'd never have even heard put together the last time that we sat down 2021 and certainly not in 2019. Yeah, what's your opinion on jail piece? In general, I'm very favourable that the number of Studies that come out are showing that they're actually quite useful especially micro dosing for healthy people If you're obese, it's it's almost a must go talk to your doctor I think if you can't lose weight alone, please Consider using these I think obesity is the fastest way to an early grave. Certainly ages you faster But if you're if you're like you and you're already already close to optimal are they useful? I think so that there are off-target things besides obesity and metabolism. It seems to be an important brain health immune system. New things are cropping up all the time. It's as close to a longevity drug as we probably have right now given what we're seeing. Yeah, it's still early days because we need to do long-term and there are some downsides. There is increased risk of but low risk of kidney issues and even blindness. Don't panic. It doesn't happen very often. So it's still really rare. But it's not perfectly safe. So I just want to make sure people know that it's not like going out injecting candy into your anything. But I do think that and I have taken guilty ones. Small doses to see how I would feel what would happen. I definitely didn't have hunger. That was obviously what would happen and I lost weight more easily. I didn't take it long enough to be able to tell if other things were benefited. It looks like there's protection against dementia from those who are on the weight loss drugs. And this is from a mechanism other than just calorie restriction. There's something else going on. It's hard to tell because most of the people on them are already overweight. But yeah, I saw a study recently. I don't remember the journal, but I'll look it up and post it online on my social. But I did see one that had really good evidence that it was not due to weight loss. It's just, I would say in general, whenever I go to a longevity conference and there's a company like Novo Nordisk or Lily, like you should see this later study, we've shown that it does this thing that we didn't expect at all as a side effect. And it's funny these companies are now calling themselves also longevity companies. It's become that fashionable as well. I suppose anything that reduces morbidity technically in one way. I mean, people that make helmet, bike helmets are longevity companies. You know? You're right. And it's a word that's unfortunately getting overused like anti-aging was 30 years ago. And we'll have to come up with something else to pursue something sexy. Hubertman says he thinks red or true tide will be a trillion dollar drug. Dracking about that. I think it's possible. If the oral ones really look good, they may actually be even more interesting. But yeah, what is it something like 10% of Americans have either tried it or been on these drugs? I think 45% of Americans say that they would. Jerry, can you chat GPT, whatever the numbers are of GLP users and desired users in the USA. Let's find that out. But yeah, I mean, what is it? Obesity is twice as big of an issue as a starvation now globally. There are billion people that are obese and half a billion people that are starving. It's like the number one leading cause of malnutrition globally is obesity. Currently around about 11% of US adults, 29 million Americans ever used to GLP 15%. So that means that only what's that about 2/3 of people who have used one are currently using one. And 91% of Americans are aware of them. 20% of US households. Can you say how many people want to? I'm sure that this is from the most recent book that Johan Hari brought out saying that it's like 45% of Americans would either have tried or want to try them. About 40% of US adults have obesity. We'll say that my number is correct. That sounds great. I mean, the off target effect of this, it seems like people don't drink alcohol so much, though it seems they're cravings for video games and porn get curtailed sometimes. I mean, we're getting into not just neurobiology, but the framing of your own sense of self. What is your mission? I am the sort of person that is disciplined. I'm the sort of person that can do hard things. I don't need to eat that food. I'm not going to have that junk. What is the snowball effect that turns everyone into kind of a micro David Goggins because they're working hard in one area of their life and diet is usually the first frontier that people get stuck into when it comes to discipline on both sides of it, whether it's good or bad. Okay, well, maybe I'm going to get upon time. I didn't eat the junk food last night. I want a bit of a role. Yeah, maybe it was pharmacologically assisted with what I did with my discipline around food, but I'm getting up on maybe there is some super magic wizardry that's going on inside of the brain. I don't know, but it's definitely interesting. It does feel the one problem is it feels like an artificial solution to an artificial issue, which is we shouldn't have a food environment which is so hyper palatable and calorie dense and attractive that we now need to medicate our way out of this. Yeah, it is dystopian for sure. But it's a blessing that obesity is declared a disease and then companies worked on it and now we have these meds. I want aging to be the same. Aging should be declared a disease. We work on drugs and then we treat it. And in the same way that JLP ones now are saving the world, the same will be true, I believe, 20, 30 years that people will say, why didn't we treat aging earlier? What common health advice today? Do you think people will laugh out in 50 years time? Yeah, I think eating three meals and snacking that you go to the supermarket and there's health bars down the hollow aisle that you're supposed to never be hungry. That's going to be seen as extremely toxic. Your body needs to feel hungry sometimes, have a break from food. So this trend of your bad parent if your child feels hunger is going to be looked at like, what are we doing to our kids? Do you think A.I. is going to make bigger inroads into longevity research? I don't know why. I mean, again, you know, 70 years ago when we sat down, A.I., you were with your snail. You're drawing a fucking snail on the whiteboard. There was no A.I. to be found. I don't remember what the snail was. I asked you about it at the time. And it was something to do. It was explaining. It was some nerd stuff. This is how the molecular something something. Oh, I remember. We said, Chris is coming. Let's draw a snail through a fucking snail. Easy. The idiot British guy will get him in and it'll be convinced that it's actually something really important. What say I doing to longevity research? Yeah. Well, you asked me, do I think I know it's having a big impact already on research. My lab is thriving on it. It's going way faster. We just did something in a few months that would have taken us a hundred and sixty years. And that was like, that's using old technology. That these days we can do. I'll tell you a story that's funny. On Friday, I had a meeting with a student that just came to my lab over the summer. And he's been here maybe three weeks. And he's 19 years old. And I gave him a task. I said, according to the information theory of aging, if you look at all this data that's out there that nobody's looked at in a certain way, it should have this signature. And if it has that signature, we might be right. We might have found the backup copy to the software. And I said, okay, that that's your task. Go go do that thinking, you know, how that'll take you the next five years. Yeah. Exactly. Because I've had about three people in my lab try to do that. And they were not really successful. And he came in on Friday. And he's with his team and his mentors. And we sat in my office. And they've all got this big grid on their face. And they threw up on the LCD screen in my office. The results. And this wasn't just the usual. I wrote some code in R and ran it. And we got some graphs. This was truly using AI. He was using one of the leading AI models. And he presented it like it was already published work with beautiful graphs and looking at terabytes of data that's out there in a new way. And he found something that professors and the experts in the field have missed for the last 10 years. And it's right there. There's this signature goes, I've given it a new name because I didn't know what to call it. This signature. I'm calling it the reverse tail. I said, what the heck is a reverse tail? And he said, ah, well, I called it this because of that. And I said, dumb name. We'll think of a new name for it. But it's a lovely idea at ship branding. Yeah. We'll work on branding later. But the fact that you found it is incredible. And that's a 19 year old. Are he just finished high school? And with AI, he's going to revolutionize biology, I believe. And that's just one kid. Imagine when whole teams are doing this. That's wild. That's why it's so. Have you, has there been anything as far as you're aware in the field of longevity that's been generated or inspired by AI that has gotten itself to trials, testing and fully published as a world changer is we still at the frontier of that not meeting the real world yet? We're undergoing this revolution. So tomorrow's going to be better than yesterday. But we're now at a point where almost somebody on their phone can discover a drug candidate, whereas it would have taken a pharmaceutical company years and hundreds of millions of dollars. It's that world. We can go from now that Demis Hasavis has and his team, not just him, has cracked the code for protein folding. We now know all the chess pieces. We were guessing and it took years to find out what one chess piece looked like and there's over 15,000 of these pieces now. These are all now modeled in 3D. Now we know not just how they look in 3D because they used to be one-dimensional based on the DNA. Now we've got three-dimensional amino acid structures. Now we're seeing how they fit together. Computer is actually smart enough to figure out which ones dock with each other and eventually we'll figure out how they're all working together. An artificial AI version of a cell, we can do in silico experiments at the molecular level now and dock trillions, last year it was billions. Now this year it's trillions of chemicals, real drugs and imaginary drugs. It's kind of like a virtual environment. It's like a virtual lab. Yeah. Are these accurate? So if I run the synthetic lab, is it one-to-one with the real world? It's not one-to-one but it increases your odds exponentially. Because you don't need to do test, test, test. Okay, maybe this. You can discount a lot and then the interesting ones get moved into the real world. Yeah. And the old way of doing it which felt really modern was you have libraries of little plates, hundreds of these little plates with 96 or sometimes the 3.84 little wells and each one has a different chemical. This physically in a freezer somewhere you have to pull it out, give it to the robot, the robot then does its work overnight, tests it on cells, take a picture of the cells. This kind of work is slow compared to today which is we don't even need to have the fridge. We can make up trillions of potential drugs, test them, run it for a few weeks. It'll tell us here's the top 200 and probably at least half of them are pretty good. It feels fucking primitive. And now we can do that experiment with hundreds instead of trillions. And trillions is impossible by the way. The most pharmaceutical company with screen would be in the millions. Now we do trillions. And then you can even order them online. That's the thing that blows me away. We got a set of 200 that we think can reverse aging using AI. And then I thought it's going to take us a long time to synthesize these 200. No, we just order them up. The company can make them for us in a matter of weeks. Now we've got them in the lab. We're testing them on human cells. We've developed an AI system that can tell us whether the 90-year-old skin cells from a human are going back to being 20 or anything in between. Just by looking at them, we paint them with dyes, different colors. And then where we're at is hopefully in the next month or so. Give it two months. We will have a set of chemicals that can replace the current cocktail that reverses aging in the mouse. If you're paying attention earlier, not you, but listeners, if you've just joined us, I was talking about we've got things that we can give a pill or a swallowing thing, a drink to a mouse, swallowing thing, a drink to a mouse, and it reverses its age. We've got that, but it's a cocktail, a very secret cocktail, but it's got at least three things in it. We want to bring it down to one and turn it into either a supplement or a drug or a patch or a certain kind of cream or all of the above, but we're getting really close to being able to have the single molecule that can truly safely reverse aging in human cells. We'll test it on the mice and we'll run from there. How big of a role is expectation in how someone lives? If somebody thinks about aging is being associated with frailty and degeneration, can actually make them live less long? Oh, you mean mentally, if they're, yeah, that's well studied. If you're optimistic and you're enjoying life and you don't just get retired, just retire and be bored. Yeah, mental attitude is huge. Robert Voldinger, a Harvard scientist, has found that the mental attitude and your social life is as important as you blood pressure and cholesterol. If not, it's more important. And the one thing that was the best was have a reliable partner. I went through a divorce, it was horrific during COVID, and I believe that it took years of my life. So it felt like it anyway, but it was it was a shock. I didn't know it was coming, but it's brutal. Anyone that is young, getting married, just beware. We all change over decades. So that's something to keep in mind. But the point there is the amount of stress and cortisol that runs through your body when you have a really big life event, moving house, breakups, death in the family, your own illness. These are age accelerators. And on the other hand, we've talked about today, the kind of things that keep you healthy, the exercise, the diet, the social life, the sleep, the relaxation, these are all we know are likely to not just slow aging, but eventually keep you disease free. And I do want to mention that. Often people think, oh, I don't want to live longer because I don't want to be old for longer. That's not what we're talking about. We're talking about still be young and vigorous in your 90s. My father is almost 90s, 87 now. He'll be here on Friday from Australia. It'll be, I think, second or third time. He's come to the US. He was just in Japan. This is not a typical 87-year-old. He is living life probably better than he did in his 40s. He's out every night with different people, mostly women that he's excited about. Not the good friends. I won't I don't want to disparage my father. He's not a dirty man. But he is a very sociable guy. And in his 40s, he was raising me and I wasn't easy to raise. I was a pain in the gut. He will say he's never had a better time in his life than now at 87. If you were 35 or 40 again and you could only do two or three things for longevity, what would they be? Definitely don't overeat. Be lean. Watch your weight. Have a BMI of around, let's say, 22, 24. Make sure you don't get overweight. Obviously, don't over drink and don't smoke. These are clearly really the worst things you can do. Having lost a mother to smoking. So don't eat too much. Try to skip meals. Work out, maintain a very good body mass and exercise. Those are the fundamentals. Everyone will tell you that. What I didn't realize till I was in my 50s was how important food is. I thought vegetables were a garnish for meat. I love meat. They taste great. But I've switched over to being more plant focused and I've seen a great improvement in my overall health and biomarkers. So those are good. Learn not to stress. We've talked about that took me a long time to learn that as well. But I've never been healthier because it's been slower. I've learned how to do all these things really well. I'm going to do a lightning round. So an ascendant or two, give me your review on these interventions for longevity. Okay. Okay. Creatine. We're doing how are we scoring? Just however you want. Give me a review. Yes. No. Like it. Don't like it useless. Buy it. Do whatever you think. Whatever you don't. All right. So creatine in favor of it and take it stem cells. Interesting. And if you have a certain condition, like a joint that needs repair can be helpful, but it's not long-term solution. Sea pat machine. Really important for folks that have anoxia, lack oxygen at night for the brain. Though you could try other methods, which is lose weight. Don't drink. Get a thin pillow. Try to sleep on your stomach. Hyperbaric oxygen therapy. In favor of this good evidence that certainly cycling up and down in pressure is good for the brain and blood flow and I've done it myself and have seen improvements in wound healing in others. So yeah, in general, it's a plus. Blue light glasses. Yeah. You mean yellow, blue light blocking glasses. I prefer to turn down the brightness of the lights at night and have a TV that's not so bright. But yes, I think they were much more fashionable five years ago, but I still use them. So yes, but definitely in general, watch out for bright light at night, but try to get violet and blue light in the morning. It's very important. A friend of mine in Japan found that if you don't see violet light and your mouse, you get short sightedness. So early morning light can be protective like your eyes? Yeah, and we live indoors and we don't get enough of it from LEDs. Okay, glucose monitors. Love them. They're really good. Yeah, I think that we should all be empowered by our own data. Anyone who says I don't want to know about my biology, I think, I don't agree with that. The CGMs have been very useful personally. I can see how I react to foods and I was surprised, um, grapes send me through the roof, white rice through the roof. I remember the great thing. Potatoes. Yeah, and it's still true. I'm wearing one right now. I wear them fairly regularly. The other thing that surprised me about CGMs was I gave one to my son who at the time was I think 17 and we had a competition who can have the best blood glucose levels and he would eat a lot of bad stuff. It changed his life. He is eating much healthier. He's now aware of what food does to his body. Now, I'm not saying go give it to children, but I do think there's an education and a behavioral change that can come with CGMs that I think you mentioned earlier today can really make a difference. Therapy. You mean just general psychology psychotherapy? Well, I think it depends on the person and the therapist. I think that talking about your problems can really help. I think it can be overused as a friend. I've tried everything. I didn't find a lot of the therapist to be that useful. I found it better to read books and listen to experts. But I do think therapy is very important. I've had kids that benefited from therapy. It's very hard being a teenager these days with the pressures. So yeah, the thumbs up for therapy though, make sure you have a therapist that is well qualified and provides benefits rather than just listens to your complaints. Grounding. What do you mean? Grounding. Walking on grass, negative electric discharge stuff. I don't think that's scientifically based, but I do think getting out in nature and touching our nature, smelling nature, listening to nature is very valuable. Our body will turn out to respond in ways that we don't even understand yet. Marriage. Be careful who you marry. Know that it's not always forever. Know that people change over decades. Know that it's a long-term investment. Be loyal. Never lie. And if kids are involved, try to work it out. Mouth taping. And mouth taping. So I do snore if I have a thick pillow or eat certain supplements at night I've found. So I have tried mouth taping and serena says I make even more noises, gasping. So I don't use mouth tap. I do use those nose strips because she thinks they help. But no, I haven't had success myself with mouth taping. Testosterone therapy. I prefer natural versions. If you can't raise it naturally year for older people, there's been a lot of benefits. I mentioned Shelley Basin as a scientist that's worked on NMN. He's also done a lot of testosterone work, which shows benefits, but it doesn't extend lifespan. There was no evidence that it does that for longevity. How do you talk to a lot today about supplements, lifestyle interventions, breast recovery, what the future is going to look like, AI, GLPs. Something that we never got to talk about when we knew first sat down with the perils of overoptimization. I think that it was so frontier-y in 2019, everything was new and exciting and you couldn't really be drowning in data in the same ways you can now. And I wonder what you've come to believe about the negative health implications of caring too much about your health, of overoptimizing, of the neuroticism taking away not only your enjoyment from life, but the effects of supposedly all of the interventions that you're actually trying to do. How do you come to think about overoptimization? Well, obsession about anything as possible and also deleterious to health. So if you have those tendencies, be careful. It's true for anything. Social media use as well. And I can be obsessed. What I've done myself, which I recommend, is treat it like a hobby. It's fine. It's not too serious. You're not going to die if you didn't sleep well last night. And everything's challenged. My meals are an experiment, not always. Sometimes it's a failed experiment. But I live my life like it's a journey and it's fun and I'm testing things. And so don't get too obsessed if you are not perfect when none of us are ever perfect and none of us are going to live forever in my opinion. So enjoy the journey. Do as best you can to stress. Heck yeah. David St. Claude, ladies and gentlemen, David, you're awesome. I appreciate you seven years later. Where should people go to check out everything that you've got going on? Well, the big one is lifespan.com. Become a member. Get the magazine. Learn how to live longer. And we'll learn together. We'll do some big things together. And I'm on social media. You can see what I do. Podcast season. Podcast is big. So that's on YouTube and all podcast. That's called lifespan. With Dr. David St. Claude, we have we're building we're about half a million followers, not like you, but we're good there. We did take some time off to do the trial, but we're back. And even better now. So join us there to thank Chris. Appreciate you mate. Like until next time. All right, goodbye my beauties. Dude, yes. So good.