“Age Reversal Is Coming.” Everything You Need To Know - Dr David Sinclair

The first ever podcast episode that I recorded in America was with you >> in 2019. >> Yeah. >> 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 7 years ago. >> Yeah. I don't remember it well. Uh when you were 12, right? >> I was 12. Yeah. Correct. Yeah. Uh it was very clear in from those days that you were going to be a big success. You're smart, driven, came prepared. Uh and look, this is beautiful now. Full circle. Yeah. I had I didn't realize uh Starbucks Venti has way more caffeine in than the British equivalent and it took my [ __ ] face off. I was sat opposite you trying to think about Yamanaka factors and how important NAD and resveratrol in 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. You the Yamanaka factors, what's happening with NAD and resveratrol news discoveries. I before we get into that though, what discoveries have excited you most since 2019? >> Gee, uh, a lot. I 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 a It's like the Willy Wonka. You've been there so you know what it's like. It's unparalleled. I wish wish everyone could come visit. Um 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 its blindness. That was pretty big cover of nature. It's what most scientists dream of in their lifetime. So that was a pretty big high. Since then, uh 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 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. Um, this is a gene therapy. So we're introducing genes that are very powerful. They're called Yamanaka factors. You mentioned them. And but we use a subset of them that don't cause any trouble. If you just use what Professor Yamanaka used, it's not going to be very healthy. It's 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. Um, and uh the eye is where it's most been tested. And so, we're we did it for safety reasons, not because it would work better in the eye. In fact, I told my student at the time, Wang, that he was crazy to try to cure blindness. Why not do something easy like the liver? But he said, you know, the eye is 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? >> The one about that we've gone into humans. >> Mhm. Uh well I think most people thought the aging field was a lot lot further behind. You know 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 we'd been doing this and expecting it for a while. In fact we made the discovery back uh in 2016 17. 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 fix? So this is the the thing that makes me super excited is that every piece of or type of damage and disease that's that's been tested in animals uh not just mice but larger animals it's worked to improve the vision of either a disease or damage. So for instance if you pinch the nerve uh you laser it or you give a mouse glaucoma pressure in the eye uh 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 uh glaucoma the two leading causes of blindness in the world both of them are really really easily treated by this uh new uh mechanism we call the drug ER 100 which is epigenetic reversal 100. >> Mhm. >> Um but yeah, pretty much any disease or injury could theoretically be fixed treated uh by this technology. >> Any theor theoretically any disease or injury could be treated by this >> well in the eye. Um but even beyond that the liver motor neuron so ALS uh the brain has been reversed in aging memory comes back uh even joints. There was a Chinese study that came out recently looked very good. You they used our technology to rebuild bone and cartilage in in uh 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? >> Uh not you but uh I don't think anybody listening is a simpleton but it it's actually quite simple. The 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 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 epiggenome. It's separate from the genome, which is the DNA. The epigenome sits on top of that and controls the DNA. So, in in my book, Lifespan, it's a little dated now, but you might remember I chose a CD as the analogy. The epiggenome is the reader of the music and the DNA is the music itself. And aging is a scratch CD. So for those listeners and viewers who don't really know what a CD is, there are really cool things we could put 20 songs on. But a better analogy now would be your phone has software. You know, a really old phone is slow. It can be corrupted, can get o, you know, over overused. Um, and so we can reboot that. And we we found that these three genes that we put in, which we call OS and K for short, these Yamanaka genes, trigger a program that embryos normally used to reset their age or something very similar to that program. >> Um 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 epiggenome, the software needs a reset to go back to being young again. And that happens. >> No way. >> It's it's a fact. It's shocking, but true. young very young embryos are old and then they get reset. So the 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 cuz it's 6 ft long has to fit into a microscopic little little ball and uh 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 this bundling and opening of DNA is what the epiggenome does. And my theory called the information theory of aging said that this pattern pattern of bundle loop bundle loop which is different for every cell type gets corrupted gets eroded during aging and that literally is aging. Mhm. >> 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. Uh 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, uh we started working on reversing that process, which is how we get to here. >> Yeah. 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 we believe we understand that it is very treatable or at least slowable. Um, so I think it's a useful way to look at aging as something that we should address. Um, even starting early in life to try to slow it down at least. Um, we all need to stick around for longer cuz the technology that's coming is incredible. Um, and I proposed this in my book and uh, 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. Um, but I'm glad uh Matt, my co-author of Mal Plant, convinced me we should go for it. Actually, that was his main role besides writing was to say, "David, >> go for it. >> Just do it cuz don't worry what your colleagues will say cuz some of them can be pretty brutal." >> So, we put it in there and uh 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 did 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 or AGI. We when we show and it's a matter of when, not if, that aging is reversible in humans, cuz it works in all these other animals. It'll work in us. We're basically just slightly more intelligent monkeys and it works fine in 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 going to be big like AI when that happens. But these technologies, let's say it works in the eye, and now we can treat perhaps cure most types of blindness. Then we're going to we're already doing this. I should, you know, 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. Um, and we can do this in mice easily in my lab now and others have done this and >> every cell in a single organism. >> Oh, well, 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. can't do that. You can we can basically at best get it into half of the cells, but still a lot of them. >> Mhm. >> Um we've taken a a path that's a little different now. You know how 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. Um I can reveal that over the last 5 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 chew on the pill, we give it down their throat for 3 days a week for a month. Uh, and we see that they are uh uh rejuvenated in many ways, including um not just their memory, but things like even their skin quality. >> What does what what's happening? What what's the pill doing to them? >> Well, that's a lot of work. Uh we're still trying to figure that out. But we >> So you know it works, but you don't necessarily know why or how it works. >> Well, we we actually literally don't know how the genes that are in the eye of humans now work really. That's a big question in in my lab uh is trying to answer where is this backup copy of software. Um but we do know it works. That's the hard part. And then figuring out how it works will be important to make these drugs even better and more powerful and more potent and longerlasting. But what we do know is that the epigenome is involved in the pill, not just in the gene therapy because we can disrupt that uh polishing of the CD or the reset of the software. >> Um there are genes called TETS uh which make proteins that strip uh away chemicals off DNA. These are key to the epiggenome reset in embryos as well as in our bodies. and we can get rid of them or inhibit them with a chemical um and we can feed those to the mice or give it to the cells and we have some good evidence um 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 oh the cells are getting stressed out by the chemicals and they fight back and they live longer. It's it's not that. It's truly through this reset mechanism and we can show that >> by getting rid of these TET enzymes that strip chemicals off the DNA and 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? >> Uh well the question is when uh I think that ultimately there is no upper limit to human life there. 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 and our epiggenome. But you know we have control this century over our own biology. We don't have to just be at the whim of what evolution and the serenetti gave us. And I see and 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 it's beyond technology that I can think of. Uh, but I do think that some of us will have a chance to live decades longer and probably the first person to live to 150 is already alive. >> First person to live to 150 is already alive. >> Yeah. I'm I'm not the only one in my field saying that. It's it's now realistic. I mean, think about it this way. It's hard to imagine the future, right? But the 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. >> Mhm. 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 not the way it works? >> Well, we we made sure that wouldn't happen. That was one of the the things that one changen everybody into a >> Yeah. Well, that was the >> embriionic death. >> Okay. Yamanaka um 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 die within a couple of days and and in fact if you do that to an animal it's tra it it tragically does die or get 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 erases it >> and my student Wang uh 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 were 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 cuz we know wouldn't be talking about it now. Um 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 CMIC. We call it M. without M, the M gene, cells don't go back 100%. They go back about 75 and stop. >> And and that was the breakthrough. The stop was really hard to find. Uh but it's there. And >> you just turn everything into stem cells. >> Yeah. Yeah. Or cancer. It's even worse. Um >> well, maybe not not worse, but it's definitely bad. You're not going to live longer or cure blindness. >> But that was a breakthrough. And and one sent me the pictures of the cells that were 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 won't say 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 way more than I should, which is again not a fair thing cuz my lab is 8 years ahead of what we've published. Um, but I think most 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. Uh, I've been told by some of my colleagues, don't say that number 150. It makes us look bad, you know, and I'll say, well, do you believe in it? Yeah, but we can't say that cuz we're scientists and we'll lose credibility. >> So, yeah, I think a lot of the science scientists are very cautious by nature, by the profession. I'm considered an outlier speaking my mind and what I believe in, but most scientists don't cuz it uh it's not something scientists typically do. >> Why is it that you're seen as an outsider? Are you throwing more caution to the wind than other people? Is it that their criteria for uh evidence is 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 he published the work. So, the public knew my lab's work before other colleagues had seen it. Um, that's also rare. Another reason why uh I'm a bit of an outsider is um I'm not doing this to be a scientist. I'm doing this because I'm on a mission and my life is irrelevant. Um I would literally die to achieve this mission. And so, you know, if I get criticized or if I speak my mind, I really really don't care. >> What's the mission? >> Uh to impact in a positive way as many lives as possible. Um this was since I was uh 4 years old. My grandmother gave that mission to me cuz she lived through World War II and the aftermath in Europe. And uh 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 uh I want to die knowing that I've done the most for humanity that I could possibly do. And and if it upsets a few people, I don't care. 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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 or heading to drinkag1.com/modernwisdom. That's drinkagg.com/modernwisdom. Longevity is a huge field, right? It 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 as contributing to their lifespan? >> Yeah. So, I talk about this on on my YouTube as well. So, there's a lot of detail on there now and I've relaunched it. >> 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 uh working on uh solving aging and now now that the clinical trials have started, I'm back to more important more important things. >> Uh but yeah, so what we talk about on the podcast is what are the 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, you're 8 years ahead. Everybody is doing the longevity escape velocity bet, right? 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 uh might miss the boat. Um it'd be tragic if you you died a few days before you know the some of these technologies came out. And this is I'm not worried about you killing over anytime soon. You're very fit. Um but you know your parents, your grandparents, think about them. So try to encourage them to live the healthy lifestyle we're going to discuss now. The buckets are uh 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 on a daily basis. It's what I do. Then there's uh drugs which some of which may work. So that's metformin, rapamy, some senolytics and probably GLP1 receptor agonist would fall into that bucket. Um and then there's supplements which is the wild west. There's a lot of things said about them. Um I believe in a few of them based on a lot of animal research and some human data. >> Uh those are the three main things uh that you should do in your daily life to maximize your chance of getting these medicines. >> Okay. Lifestyle stuff. >> Yeah. >> Last time that we were talking it was all about calorie restriction and primarily fasting as a route toward calorie restriction. >> How should people eat if they want to live as long as possible now with your 2026 data? Well, actually what I've been saying uh actually on on my podcast for now what four years uh it hasn't changed and my book lifespan which came out we were talking about when we first met in 2019 it nothing in that book I've had to revise. It's all considered >> so there's no retractions from the book in 2019. >> No. No. and my lab's 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 um if this is the first time you're seeing me uh you know let's let's start so the the main things about fasting are we know from animals um and some human data but mostly from animals that if you restrict how often you eat um and to some extent how much you you get longevity benefits. Um, and we can talk about protein ratio to carbs to fats. That's also a whole big debate as you know, but generally I 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. Um, breakfast being the most important meal of the day was General Mills, I believe. Uh, one of those companies, Kelloggs perhaps. But, uh, 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. Um, and so I try to be hungry and if I gain a little bit bit of weight, sometimes I travel and I eat well and Serena and I uh we do uh 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 for me. >> Two weeks without food. >> Yeah. Okay. I might munch on a 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, zerocalorie drinks, a lot of tea, that kind of stuff. But I can go without food for 2 weeks. It feels great. After the first 3 days, I'm over the hunger feeling. Um, I can see on my monitor, which I've got one on here. >> CGM. >> The CGM. Yep. Uh, 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's It doesn't sound like a lot. It is a lot. >> It is a lot. And I'm a regular guy. I I I'm not like some people that spend millions of dollars on their body and and measure everything. I'm kind of lazy. I I don't like being hungry. I like food. I like to snack. I I like to stay up late. I'm a typical hedenist if you let me go. Um and actually up until a year ago, I actually hadn't fasted more than 24 hours. I just couldn't do it. Like this is painful. Um and I'm stressed. So if I'm stressed, I'm going to eat. Um but what I've learned over this past year is I can go beyond 24 hours. And once I'm over 3 days, something kicks in. Actually, we know molecularly there's something called chaperone mediated autophagy or CMA, which is the deep cleanse of these misfolded and modified proteins that you want to get rid of for aging or slowing aging. >> And uh after those three days, you know, I start to feel amazing. My mind clears. Um I don't feel bloated at all. Um I don't even have to go to the toilet that often except for all the tea, but you know what I mean. And uh yeah, I feel energized and I 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 barely 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 uh a scale that measures my weight. Um it's I don't know if I can measure say the name or if it it's forbidden, but >> um I do like the Wings scale cuz >> smart scale links to the phone. >> Yeah. It will get you composition as well if you hold the handle. >> Yeah. And 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 days. >> What are you This two weeks thing is blowing my mind. What are you running on after 10 days? Are you Why is malnutrition? Are you supplementing with with vitamins and stuff so that you don't get scurvy? Like why are you not dropping dead? >> I am. I'm glad you said that, Chris, because it's important to say I'm a scientist about this. So, I'm not just willy-nilly giving up everything. >> So, you use celery and green tea, surviving for 2 weeks, just broancing it. Yeah. >> Well, no, I'm not doing that. I, uh, the reason I'm using my hands is I travel and at home I have a little carry pack with vitamins, supplements, um, 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. I know what what works. Uh, 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 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 I'm taking in things like vitamin B, uh, vitamin C as well, and some nutrients that I know I can become deficient in. >> What do you think's happening inside of your body after from day four until the day 14? What's what's going on? Well, we we know actually um not from measuring me, but we know from many years of study what happens to the human body. Uh the first 24 hours you you're going to uh use up a lot of the 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 is smarter than my eyes and my mouth. And anyone that's fasted knows that your blood sugar if you're eating is like 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. Um, or you can drink some some ketone drinks. Um, or uh it's making glucose or both. Your brain is loves ketones. And uh 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 is that 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. There's very >> I imagine it does. It turns [ __ ] invisible. >> Yeah. Right. phantom poo is a bunch of gas coming out. Um so yeah, that's what I meant. I'm not on the in the bathroom as often. It's actually much more productive. >> Um unless you're productive on >> I do find and I do I do find that the biggest obstacle to my productivity is the bathroom actually. >> Are you sure you're not you're not tweeting away down there? Uh but yeah, your microbiome I think and and this is not proven um by any means, but I feel like just like your body, it helps to give your microbiome a shake up a bit of hormmesis, which is a little bit of stress that's good for you. And uh I would love to do an experiment on myself as well, measure before, during, and after and see what happens to my microbiome >> flora and stuff like that. Well, I mean, I know that some of the proposed positive effects for GLPs include slowing motility through the gut, which actually helps with things like SIBO or candida or H. by Lori because the pace this is why every body every bro lifter that's listening to this you 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 like that's one of the proposed mechanisms I think that helps from GLPS and I don't know that's what what I was interested maybe creating this very I was going to say sterile environment it's not it's barren this completely vacant environment for 2 weeks. I have no idea what that does. It if you had a overgrowth, does it kill it all cuz 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 I do know that there's some really interesting things in bile that uh comes out more when you're fasted. M >> uh one of the components um is a a type of cholic acid which is the black black stuff that goes into your microbiome and your microbiome converts that into a molecule that goes back into your bloodstream and turns on a longevity gene that we've been working on. Uh it actually binds to the protein and makes the protein more active. It's called one. If anyone's read my book, they know what one is. Certulates the epiggenome, slows down the changes to the software. And so, long story short, it's it's at least plausible, and there's a Nature paper on this from another group that I reviewed, that 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. Um, there's abundance and adversity mode. They're both good, but you don't want to stay in one or the other. You'll you'll accelerate your aging and you'll 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? A one-day fast, a three-day fast, and what what should they do? What would be a a rough protocol to follow without having to be a a conductor of supplements? >> Yeah. Well, if if you're if you've never fasted and you just wake up and you eat a normal breakfast, lunch, dinner, either you're you're obese or you exercise a lot cuz that's going to put on weight. Um, 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 I don't mind skipping breakfast. Not everybody wants to do that cuz they work out and they feel like they need some food. Um so you can instead you can skip dinner. I would just have a very early dinner. Um what I was doing for many years, for probably 30 years of my life, was trying not to eat anything until late lunch. Um and you 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. Uh, but get get through it. And actually, after 2 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 uh of calories, zero if you can or just a little bit. Um, I do have a little bit of calories in the morning because it's good with my supplements, but um, a lot of water. So, a low calorie drink like this or water, tea, >> um, 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 is the number one recommended mitochondrial supplement on the planet. This isn't just theory. 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I know that this exists in rodents. >> Yes. um a study that was done was it macaks 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 had been given a healthy one then 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? >> Uh no. Uh 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 epiggenome, but nobody's really done a prospective study uh with placebo. It's very hard to do that or even controls. So we 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 that if you do it with nutrition, not just starving, it's very good for you. Um, 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 uh is one of my best friends and the other one is my trainee. And they were >> Oh, well, you're like in between the two of them. Yeah, I didn't really get involved. Um, but I did bring them together and they they came to the conclusion that yes, it did extend lifespan. Um, it depended on the the veterary care and other other environmental things. The University of Wisconsin where the other lab is, uh, Rosalyn Anderson is the professor that I originally trained what is it 20 years ago. uh she runs the study now and her monkeys lived longer and they also definitely incontrovertible uh 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. Um, 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 this enzyme that I mentioned earlier called one which protects the epiggenome. It responds to hunger and exercise. Um there's a molecule called NAD that a lot of your listeners and viewers would know about. This enzyme responds to NAD levels. Uh but long story short is when you're in adversity mode, your body switches from growth and reproduction into survival mode. And 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, um, 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. >> One, let's say that let's say that um somebody has 100 calories an hour for 18 hours of the day and another person has one meal that's 1,800 calories per day. >> Um there's a lot of evidence that eating within the time window is the one that's much healthier. um the friend that I mentioned earlier, Rafa Rafael Dabo 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, uh 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? >> Yeah. No, protein is good. Um, 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. Uh but the this die hard be a carnivore, forget about the green stuff is is definitely not consistent with the science of longevity. It's consistent with the science of bodybuilding and it definitely >> which of course we know is a superior science. >> Yeah. >> So the science of longevity. >> Yeah. >> Well, you know, I as much as it doesn't look like it, I really like bodybuilding over other exercise. Um I'm just busy. I used to work out a lot. Um I love bodybuilding and protein is essential for building muscle. No question. Okay. And 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. Veilene, isolucine, leucine. 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, uh they live shorter than if you give them less. And this has been shown in short-term studies in humans, if you restrict protein um 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 uh is not really the best way to live. >> I think the best way is to pulse it. Okay? So, if you're working out, you want to build muscle, yeah, you can eat you can eat meat. I eat meat occasionally. It's not a problem. But you want to have a period of your life or your let's say your day or your week where you're not eating meat or you're just not eating. Um and that puts your body at least part of the time in this adversity mode. >> Should you be doing both? Let's say that somebody's doing OMAD or 168 or some sort of fasting protocol. Would you still be looking to pulse protein intake as well separately to that? >> Yeah. I Yes. Yeah. The answer. >> So, you maybe go one day a week without protein as well? >> Well, without protein, I don't think you'll live, right? You need some protein, but you're you mean huge amounts of protein or you mean meat? >> Yeah. 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 macronutrient 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 chenino 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, uh, 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 psychopenia, 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's switched off, but you can rev it up when you want to build muscle or or uh 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. It's I just keep seeing studies that that say the same thing over and over again and then people argue about the latest one. We know that the best health is a combination of weightlifting. Uh muscle is good for hormones. It's good for not breaking bones when you get older. Um balance is important. And then the other one is aerobic V2 max. We know V2 max is correlated with very long life. Um, and so you do need to lose your breath minimum three times a week, 10 minutes. Um, it's rare that people talk about sex as a a way to exercise. I see your eyes bulging. Um, >> I'm just waiting to see where you're going to go. Well, I was looking at at at a at a tweet the other day uh at an ex whatever we call them now and it was saying oh I think I won't say who 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 well 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. >> Uh there's sometimes restrictors for that um that aren't simply cardiovascular, but go on. >> Well, you can supplement it with um you just running on a treadmill, going outside, rowing, sport, all of this stuff. Just as long as the the way to know if you're exercising enough to build up your V2 max is you shouldn't be able to carry out a conversation easily like this. >> You're panting. Um that's my judge. I need to do a lot more of it. I these days I tend to do a lot of my exercise aerobically running to catch a plane. Um I admit that I'm not the perfect role model for exercise. Um but I do know what the science says and that is the combination of the the weights, the balance uh and the aerobics. >> Uhhuh. What about zone two? You haven't mentioned low and slow. >> Well, if you can't do fast and quick and hit, uh, low and slow is fine. Walk, move, get up. Uh, I'm I'm always walking around my office. I have a standing desk. I rarely sit down. So, that kind of exercise is very good. Certainly for balance, um, overall metabolism. So, yeah, I I try not to sit at all. Um, I'm sitting now, but I rarely sit during the day. Um, it's one of the things people find weird about me. They come to my office and I'm I'm I'm pacing. I'm twitching. I'm often chewing gum. >> That's not the same as zone two, though, right? >> No. No. Need to do a little bit more than that. Um, what I like to do is a sport. Um, you know, 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. Um, yeah, a little bit. You know, kayaking is something that I like is good. I'm not out of breath, but I'm out, you know, getting a good workout, >> sleep recovery and rest. What's >> What is the most up-to-date data saying around that from a longevity? >> It's still the same. Um, it's 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 8 hours, some people need 7 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. Um, I can get away with 5 hours sleep and my HRV is still in the 80s, '90s. Um because I'm getting deep sleep. I'm not drinking caffeine late in the afternoon. Um I practice as best I can relaxation, meditation, practices breathing >> and that gets me to sleep and into REM and deep sleep pretty quickly. I also take a supplement that uh my partner Serena makes and um it's got aine and some other stuff that also I know from my own experiments gets me into deep sleep quickly. And so my efficiency is typically according to these rings uh in the 90s 90% sometimes close to 100 and then I can get away with less um which is nice cuz I travel a lot. >> I think that's the big learning that everybody who starts using a wearable takes away from it which is you're sleeping way less than you think you are. Like well you know I was in bed for 8 hours. It's like, no, you thought that you went to bed at 11:00, but it was actually sort of 11:30 and you were reading or watching TV until nearly 12:00 and then your actual efficiency was maybe 85%. So that 7 hours has turned into 545 or six or something. And yeah, it's stuck. I've got >> maybe 1,500 maybe 2,000 nights on Whoop tracked right over the years. And it's you're just always sleeping less than you think you are. Like 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. >> Yeah, I agree. And especially if you're you're eating late, drinking coffee or tea late uh or matcha. Caffeine and alcohol are big ones for bad sleep. >> Um not just stress. Having a hot room or too many blankets is another mistake that a lot of people make. Um, you can get those beds that are cool. Eight sleep is anyone that's not using an eight 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 a cool and there's other cheaper versions out there. I'm sure eight sleeps the best, but there's 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. Oh, 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 does that look like? How do you how do you come to think about stress as a longevity doctor? >> Yeah. Well, you can measure cortisol, for example, um or DHEA cortisol levels. We're all stressed. You know, the the old days of sitting around a campfire, not really there anymore. We're driving to work. We're worried about income. And so, what we want to do is uh learn to to deal with the daily stress. You know, the world is changing faster than ever. So what what I've learned personally is really not to let worries of life get me down. Um 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. Um if it gets really bad, I I go there physically and do some work. But yeah, it's it's all about learning not to ruminate. Um, and a lot of us a types, I'm sure you in your success are 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. Um, 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. And the last >> How do you How do you stop worrying? >> You have to train yourself. It's like don't be an idiot. Stop thinking about it. Um, it's not going to kill you if you distract yourself with something else. Overthinking something is is a real uh uh issue for modern life. And uh so I don't do that anymore. If I uh 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 you're uh 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, and what 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, um, you get through it. You trust yourself. You know, you know, maybe when you're a teenager and your 20s, you don't know that you can get through these things. I'm at an age where I know I'm not going to die. I'm going to get through it. It's going to be okay. um if I have a problem, I'll solve it. Um 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. 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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. Uh I thought I'd have to change things depending on the science but the science has held up. So in the morning and if you go to page uh what is it 304 of lifespan it's still still there. Uh and I still do that uh rverrol it's been back and forth controversial. It's not controversial in scientific circles. There's a few naysayers but they make a living out of it. uh rveratrol is from plants that are stressed and they activate cert one this resetter of and slower of the epiggenome uh noise. So, I've been taking about a teaspoon, call it a gram of resveratrol every morning, uh almost every morning for the last gee, probably 20 years. Doing all right. Um it seems to help in clinical trials. It's been tested in a number of clinical trials. I mix it with either a little bit of olive oil, that's my calories. Um or, uh Greek yogurt or vegan yogurt, and uh it's been good to me. Um I also take that with uh NMN which is an NAD supplement. It's a precursor. We studied both in my lab and uh we just resubmitted a paper. This is something I can reveal. We just resubmitted a paper uh 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 uh so that'll come out probably >> resubmitted. >> Yeah. We 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 What was the controversy? Because I know since the last time we spoke there's been some fur around resveratrol, some more fur around NAD, maybe NMN as well. Yeah. Can you explain what happened? >> Yeah, sure. These are all typhoons in a teacup or whatever it is. >> I can't stop drinking your drinks. Very good. >> Good. That's all I needed. the uh so let's start with resveratrol I try not to bore everybody um so one is an enzyme I'll use my hands it's an enzyme that carries out reactions that stabilizes the epiggenome so it doesn't decay so think of it as stopping the corruption of the software more one is better so there are two ways to activate one um with with a pill rather than exercise and dieting um and if you do all of them I think it's the best so you can either take resveratrol and that we showed in 2003, long time ago. I'm old, uh, activates one directly. So, the enzyme is removing chemicals from the epiggenome and making it stable and it can do it slowly. You know what a Pac-Man is, you're old enough. Uh, so it's chewing away uh, chemicals, stabilizing things faster the better. Whereas virtual we know binds physically to the enzyme and now makes it chomp faster. Okay. The controversy that came up was that Fizer, a team at Fizer, not the whole company, just a group in the company, put out a paper in 2010 that said resveratrol doesn't do this. It it must be an artifact. It's doing something else that makes it look like this. Um, so we then spent 3 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 resvertal 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 FISA was wrong. Um and we've put out papers since and others have shown that we were right. So no controversy. >> Going headto-head with FISA is no small task. >> It was brutal. Uh, that was one of the hardest things in my life because I remember try to def trying to defend myself in public. >> It was on NBC and I said, "I'm not sure what Fiser 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 Fizer. Fizer knows what they're doing. Um, I will say that I don't have ill will towards those scientists because it's a the job of scientists to challenge theories. Um, 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 FISA, what is the remnant argument? >> There isn't one. The the problem is that the the 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. Um, but in scientific circles, everyone's read our science paper uh from 2013 and it's not debated. >> That's put to rest 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 theory, you know, we're we're done here. >> Okay. And what happened with NAD NMN? >> Uh, so yeah, the let's bring everyone up to speed on what NAD is. So C one also can be activated by giving it fuel, which is NAD. or one chomps with NAD. Um, and in fact, this is not often known. The chemical that it takes off the epiggenome 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, uh, you see more stable and healthier cells. um 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 mean the field not just my lab that raising NAD levels above normal baseline is very good for humans. Okay, I can give you examples. Um Shelley Bas you could look up uh in PubMed he's got a couple of really good papers giving uh NMN which is the precursor to NAD to people that are either obese uh or have diabet pre-diabetes or even super fit ones. Um maybe the super fit isn't published yet but he's done the work and reported about it. Um you see improvements from lipids whole bunch of lipids uh cholesterol blood pressure body weight. So raising NAD, I think most people would would say that it's good for for humans and animals. Okay. 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, um, somebody showed that human blood levels in white blood cells, the white blood cells don't have less NAD as you get older. So some people who love to make a living of being naysayers especially towards my career uh 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 we've known for probably a decade that that was true and it doesn't affect the theory. We know that raising NAD levels in humans either by exercise uh 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 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. How what's how's that classified? >> Yeah. Um, oh, just a final thought. There is a really good study that showed that people who have lower levels of NAD in their muscle um I think it was are not as metabolically active as those that have higher levels and >> or they had metabolic syndrome. Anyway, we could check it out but but there is some good correlations between NAD levels and and age related conditions. Want to be accurate. All right. So the FDA thing um 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 cuz 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 uh 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 will have that happy world. Um the legal team at Metro Biotech made a decision without my approval, actually with my disapproval to um write a letter to the FDA pointing out that it that there was this law that they shouldn't have simultaneously sales and clinical trials. I I objected. Um the FDA uh initially said you shouldn't be selling uh 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. >> It No, I mean the opposite. The FDA I believe says it's okay to have Nmen on sale now. >> Oh, interesting. Okay. >> There was a court case uh 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. 80. The 81 milligrams, though. 81 is is only because a trial did 81. It's not magical. >> Brilliant. >> But yeah, you could take 100 probably. Um, 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 uh lowering the amount of uh 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. You know, everybody's different. So I I believe in precision medicine and there's a group of people for example that where it does make sense to take baby aspirin. It's been shown that there can be benefits and it's those people just as an example who have high levels of lipoprotein A or LP little A. >> Um I'm one of them. So I continue to take baby aspirin. But these are decisions to make with your physician. >> What else? I I can't work out whether we call resveratrol a supplement or a drug or a pharmaceutical. I'm sure you can get it in pharma grade, but there's >> What else from the not foods consumption stack are you taking? Because aspirin would definitely be in the sort of meds >> category, I suppose. What have we missed off? >> Well, there's whole websites 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 or people can listen to my podcast. Yes. >> Because it's a whole it's a whole box of things and I'm not taking them all the same day. Um, but I still like um um alpha lipoic acid for mitochondrial health. So, I've been taking that uh for over a decade now. I did a PhD on it, so I know a little bit about its benefits. Uh, but that was a long time ago. Um, let's see. CoQ10, of course, cuz I'm I'm actually on a statin. I might switch to a PCSK9 inhibitor because it's more effective, but my family is very high cost. >> I'm on I'm on Rapatha. >> Great. >> Yeah. >> You like it? >> Uh I've actually stopped taking Rapatha because I want to see if it's causing some brain fog. >> Oh, that is sometimes associated. It's anecdotal. Uh but I noticed Apo B went through the floor. [ __ ] 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 found Rapatha largely it's every I've got the every two weeks one rather than the monthly and that's been good. But I've also been taking Telmarten as well because uh 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. Um, I have every polymorphism under the sun for somebody that's going to have high cholesterol and high blood pressure. Like just a really perfect suite of hyperabsor, hyper retainer, all of the dispositions that you want. >> Are you on zedia? >> No. What's that? >> Uh, the drug that's the common name. Um, I thought I'd use it. Uh, it is the drug that blocks uptake of cholesterol. So, the combination of a statin and um the Zedia has been shown to be very effective at lowering 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 Momenus. 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I did carnivore toward the back end of 2024. Meat and fruit technically for 6 n 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, right? Without any starch or carbs to sort of really bring you into land. >> Uh, and I managed to get my cholesterol up into the 400s, which >> 400s. >> Yep. Yeah. It was really impressive. It was kind of like a personal only briefly. Um, and then had creamy blood >> and then brought it back down. Um but it's kind of what I've come to you're right to say that uh everybody is different. Everybody has a different system. And the fascinating thing when you do these sorts of playing around with self-experimentation and intervention is you find out there's something that can make you feel amazing, make you look amazing. It's like in all of the subjective metrics that I care about, >> right? 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 [ __ ] unbelievable technology. By the way, the basically this special type of uh contrast scan is able to look inside of the uh arteries of your heart and look at plaque buildup without having to do anything invasive. It's magic. And I'd had a small, very small, but mild amount of plaque progression. I'm like, "Okay, I need to put the kaibos on this regardless of how jacked and alert I feel. I need to eat a much more sort of Mediterranean low fat, low protein diet." >> Yeah. >> Um, and I know it's not proven, but uh I do like the idea of uh pluck 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, Rapatha, that kind of drug. Um there's an oral um PCSK9 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. Uh and then the second one uh 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. Uh nattokynise. Do you know about nattokynese? >> No. Uh, so do you know what natto is? >> It's 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 lift it up, it looks like cobwebs. >> Okay. >> 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 basillus subtilus and some other bacteria eating soybeans. They found that there's an enzyme in that stuff that if you swallow it, it can remove, well, at least it looks like it can remove plaque. Hence, nattokinise. Kinase is the enzyme. Natto is the the food. >> And so I I swallow uh depending on the day about 10,000 units of this stuff >> every morning. And I'm going to >> some sort of capsule. It's just a capsule. You swallow it >> right >> in the morning and I'm going to measure it. Um I typically do an ultrasound on my corateed every year. Um similar it's like the clearly it's just uh on your neck and uh you can actually do your um 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 cardiovascularly for your whole body >> and I'm going to see if nattokinise makes a difference. >> Fascinating. What's all this hype around erectile dysfunction medication? >> That's a lead in question. Um, well, yes, it's recently come into social media because it was found that that that uh 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. Uh, and I tweeted out what's not to love and it millions of people saw that. Um, but I'm serious. I I take uh uh what is it? Um, seialis is the common name um to del um every morning a low dose. It's just uh a little bit and I I do that because in 2012 we published a paper that showed that one of the the most pernicious causes of aging is low blood flow. And then we could reverse that with NMN through cert one more blood flow. And it's really underappreciated how much a lack of blood flow leads to diseases. Your especially your 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 >> it was an angina medication, wasn't it? >> Exactly. >> Do you know the story of why they realized it had that side effect? >> Um, was it was it pulmonary when when they were doing the the trial, typically you do a a meds 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 nurses noticed that the uh patients when they were doing their interviews were sitting cross-legged >> and they had this strange >> contorting of their posture to try and hide the fact that they all had hardons. Yeah. >> And uh it they said, "Hey, we we the angina thing we're not so sure about, but we've done some wonderful stuff to the penis." >> Yeah. Well, I I can say taking a low dose, the good news is it doesn't make your your penis get erect without warning. that isn't a problem. >> But the low dose really um let's put it this way I haven't had any downsides yet. >> Fantastic. >> There's 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 um so there's a there's a study in mice 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 uh continuing to get blood flow in my hair follicles will keep my hair >> more hard on less balding. That's the equation. >> Yeah. I 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. Uh human had said something to do with the uh perusion of the prostate as well. uh that opening up blood flow is is especially given how close you are to ground zero might be a like a useful side effect. It's I don't know man. I I said my favorite conspiracy theory about this I I hope that it's working. I hope that it's a a like pretty much all gains intervention that everybody can use. But my favorite conspiracy theory about why erectile dysfunction medication is being pushed so hard is that it reduces any of the stigma of any one guy having to take it. that darling I've got to take it. It's important for my hair. Dr. David Sinclair told me that it would stop me from going bald. And also, you know, great grandma, she had she had Alzheimer's. It's very important for my neuro degeneration. And my you don't want the prostate, you know, granddad, he had the prostate thing. So, it's the the ED. You don't need to worry about that. It's normalizing. >> There's a lot. I think you're 100% right. And uh I'm sure there have been some wives like, "Honey, why are you eating 10 of them?" >> Yeah. Yeah. Um what about omega-3s? You know, omega-3s commonly touted as something that's very important for people's longevity. Where'd you come in to land on omega-3 levels and supplementation? >> Uh, I take an omega-3. Um, the the data looks really pretty good that uh if you have some of that, it's anti-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 are the best. >> Um I do like I do like them. >> Yep. >> Um their products are really pure and distilled. So you want to avoid the cadmium and lead products. >> The what what >> the ones that have heavy metals. >> Okay. So I I mean I remember this. My mom would tell me this 25 years ago when I was a kid and she would be taking her and there would always be this line of lowquality 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 [ __ ] ancient wisdom. >> It It really is. And actually, while we're on the topic of um contamination, I uh and other labs have measured uh supplements and they're often contaminated with things and I even got sucked into a lawsuit because I said I tested this product and it or this type of product and it had contamination. But I I do want to say at the risk of some ligious 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. Well 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. Um, she's out of Singapore. She found that a lot of the NMN supplements didn't have NN in it. And if they did, it was a low 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 live longer, which is not going to work if it's contaminated. >> Hang on. 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 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 blow up the internet. Might might bring it down, but um I will say that to help the viewers um the and 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 um you know 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. Um, GMP is important always. Any supplement should be uh good manufacturing practices. Um, USB label. Look for those badges of purity. Um, 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 batch?" >> They often do that, >> right? 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. Um, and so what, um, and I'm going to do a shameless plug if that's okay. Um, 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. Um, and I hope that it becomes the world's largest longevity community. >> What does the what what's the community built around? What is it? >> Yeah, it's called lifespan.com. So, my show is lifespan. This is the website version. Um my goal ultimately is to fix healthcare across the planet. We've done a top- down government big industry HMO. Um we know that doesn't work. The US especially is spending close to 20% of GDP on their healthcare and got some of the worst healthcare. So they got to do something. So grassroots movement lifespan.com will be a community that comes together to learn what works, what doesn't. Um and eventually where I want to take this is that we we change how healthcare is done and with AI with knowledge with you 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 um that's cool it's probably launched by now >> um there's for members so that there's an unpaid You can do show notes and you can see some uh some stuff. But if you um pay the $8 a month, um 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 uh newspaper or reporter who doesn't know anything who also wants clickbait. Um 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 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. Oh, >> that's 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. >> Yeah, have a look inside. I'm so proud of how it looks now. Um, 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 and it's very beautifully put together. Beyond your birthday, Steve Horvath on the science of epigenetic aging. I know Steve Horvath. >> Yeah. Yeah. Steve discovered the epigenetic clock. >> Can a simple multivitamin mineral supplement slow down aging? This is awesome. Congratulations. >> Thank you. I'm very proud of the team. It's a 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. Uh okay. Other interventions, other stuff that's happened cuz since we since we first sat down, the world of longevity, biohacking has really sort of it's not exploded. I think it's I think it's become more sophisticated. You may say otherwise. The evidence may say otherwise, but at least from the like self-experimentation, uh, you know, 2017, 18,19, >> it was a lot of the biohackers handbook. It was, you know, Ben Greenfield, friend of the show, sticking ultrasound things on his penis to see if he can improve his his erection quality and his orgasm length and stuff. And then it seems like it's really come on databacked a lot more. Um, evidence-based crowd stepping into this. >> Well, thank you to to you. For example, uh guys like you are bringing scientists like me and people who know what they're talking about so the 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 in Greenfield's case, like how right he was about tons of stuff super early on. >> Yeah. So, I didn't mean to imply Ben was one of those people, >> but there's so many even uh uh Teemo Teimu 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 [ __ ] at the wall and much of it doesn't stick. >> Yeah. >> One of the most uh 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? >> Um increasingly we're learning. Um in 2019 when you and I first met there was very little evidence actually. Um and you're right by hacking was something that was looked down upon especially by doctors. um and the public didn't know what was going on. Uh then came the pandemic and most people saw their 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. >> Um but we are we are in a world now where the individual can know more about a certain topic than their own physician which is incredible. Um, that does include sauna and cold bouts. When we met 2019, there was a little bit of data in sauners and nothing on cold bouts except a mouse dunked in the cold. Um, now there's much better evidence. Um, I put it in my book lifespan because uh I was told by the editor that that would be interesting, but I was hesitant because there was such little data on sauners and and nothing on ice bs really. That's different now. I can now say as a scientist scouts honor I I was a scout I forget how we do it um that definitely sauna there's a lot of evidence mostly uh Nordic men have been studied uh 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 and and that is reproducible so that I think sauners are great >> um I try to do some of that myself um as hot as I can bear. Ice baths contrast it makes sense scientifically hasn't really been studied but uh cold therapy we do know it can activate brown fat which is very good. >> What does that mean? >> Well so we we actually going back in history 30 years ago we didn't know that we adults humans had uh brown fat. Babies have brown fat. It's a highly metabolically active type of fat in babies that keeps them warm because they can't shiver initially. Um, 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. Um, often they're in the back. You can get it more brown fat by by doing cold plunges and being cold. Um, and >> do you want more brown fat? >> Yes. So, I was going to say the the brown fat's full of mitochondria, which are healthy. They brown fat seems to secrete factors that are good for health. Um, 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. Um, but the older you get, the harder it is to to make and convert from white to brown or beige. >> And uh, so my view on that is, and that's true for mice. 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. Um, 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, uh, build up brown fat. That is a might. You will get more brown fat if you cold plunge. um and do those kind of things roll around in the the snow. It is controversial though. I did see a little bit of push back against Wimhof 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 10 to1, 20 to1. Yeah. And I It's strange because the immediacy of the reward, if anyone's had a cold shower or used a cold plunge, you feel really good. As long as you stay in for a little bit, you feel so good afterwards. But I'm I like to do it. It's fun or whatever, but I would probably take a sauna 20 times over taking a cold plunge if I'm going to try and do something for my health. >> I'm the same. I I do a hot every every day, including a a steam shower, but uh I cold plunge probably once every two weeks at best by by turning on the cold tap. What do you make of Brian Johnson's approach to longevity? >> Well, it's totally different. Um, it putting the two of us side by sides, some people do. It's it's not the same animal. Uh, I'm doing science. I'm doing the research. I'm figuring out the molecular mechanisms. Um, 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 um is in a couple of areas. He's very courageous. I like that he stuck his neck out. I I have a lot of uh admiration for those people who are brave that way. Um he's also been um helpful bringing a spotlight to the field of longevity. And I remember a lot of my colleagues uh my highbrow colleagues in longevity really said he's the worst thing that's that's happened to our to this field. He brings a bad name to longevity. But I 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. >> Um I came along, but definitely Brian got a lot of attention. And I think it's been helpful to wake people up from their stuper. Uh not everybody, but a lot of people just live their lives and eat whatever they want. um do a little bit of exercise. Brian said we can be much better 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 uh but also with an N of one doing pre-treatment, post treatment, see what happens under doctor's supervision. We can learn some things too. Um, yeah, it I I think Brian deserves a lot of credit for for that, for bringing attention to >> you've got you've got a highly unsexy field. I'm not saying Brian Johnson's sexiest guy on 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 um the fundamentals for longevity, have you got any smell test or sort of lick your finger to work out where the wind is coming from or you think, "Oh, he might really be on to something there." Is there something that he might be out ahead of where the the data or the research or the science is at the moment? >> Um, not really. I I I don't pay as much attention to him as I probably uh should or could. >> Um I do look at some of the the blood work that he posts and uh there's a particular test um that's called the Dened and pace of aging which is a measurement of your epigenome 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 a before and after or you take it every, you know, 3 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 04 something and one would be you're aging one year for every year. >> Yeah. >> And you know if you're two then you're doubling your rate of aging so you're going to die early >> according to that that's one of the lowest paces of aging I've ever seen for a human. So that's pretty impressive if that's maintained. He could live decades longer than the average human. >> He's supposed to >> than he would if he didn't take care of himself. >> Is that taking into account telomeres or no? With that Deneden pace of >> No, it's not. I I don't believe so. It's I just uh 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. Um, I think that if you're on a vegan diet, yeah, you should make sure you're not deficient in any B vitamins. Um, generally, if you're taking a lot of multi- uh what do you call it? Multivitamins, uh it's excessive and it can actually be toxic if you have too much. So vitamin C uh can be pro- oxidation, not antioxidant if you take a lot continuously. So overall, I'm not I'm not for multivitamins. Um I do believe you should measure your vitamin uh 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. think, yeah, you'll get a short-term hit, but I 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, I've 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 something else. One of the potential put forward uh explanations was well, your mean 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 said, "Okay, well, I'll try some uh intramuscular methylated B12, like 500 micrograms, tiny tiny teeny tiny little It's almost like got 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 I was trying to push back against. What I'm saying is I know what happens when you p vitamins too far. Um, and I actually did that the week, it was the biggest week of the show last year where I had Rogan. I was on Rogan on the Thursday and then recorded with Naval Ravocant on the Saturday and I went into it going, I've like poisoned myself with [ __ ] B vitamins and now I can't think straight. It was fine. It was It all ended up being great in any case, but uh yeah. Okay, so um spending too much money on uh vitamins, multivitamins is one of the biggest wastes. What else? Well, at the risk of being sued, um, I would say >> there's a big cue. >> I'm not sure about, again, I'm not saying it's wrong. I'm just not sure about uh certain laser therapy. Um, Serena, my partner, loves shooting lasers at her body. But I >> for skinincare >> uh internal as well. >> How do you shoot a laser internally? >> Well, >> which which hole does it go in? Yeah. Well, it 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. Those 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, I think that's fine. And the red light sauners. Um, I'm going to get one and see how that goes. >> But the yellow lights and the others. >> Yeah, these other things. It looks like it's Fourth of July uh in in the house, but I'm not sure about that one. Um, but you know, you have got to be careful what you say is BS now turns out to be true. >> This is where the biohackers get it right, dude. This is where the biohackers get it right. >> Yeah. Even peptides, you know, now we're seeing a lot of them are actually really helpful. >> Talk to me about JLPs 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 GLPs? >> Uh in general, I'm very favorable. The the number of studies that come out are showing that they're actually quite useful, especially micro doing for healthy people. If you're obese, it 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 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 that seem to be important. Brain health. um 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 cuz we we need to do longterm and there are some downsides. There is increased risk of but low uh risk of kidney issues and even blindness. Um don't panic. It's it doesn't happen very often. So, it's still really rare, but there it's not perfectly safe. So, I just want to make sure people know that it's not like going out injecting uh candy into you or anything. Um, but I do think that uh and I have taken GLP ones um 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. Um I didn't take it long enough to be able to tell if other things were benefited. It looks like uh there's protection against uh 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 >> it's hard to tell, right? Cuz most of the people on them are already overweight, but yeah, I saw a study recently. Um I don't remember the journal. Um, but I'll look it up and and post it online on my social. Uh, but I did see one that had really good evidence that it was not due to weight loss. It's just uh I would say in general whenever I go to a longevity conference and there's a company uh like Novo Nordisk or Lily, they're like, you should see this latest study, we've shown that it it does this thing that we didn't expect at all as a side effect. Um, and it's funny these companies are now calling themselves also longevity companies. It's become that fashionable as well. >> Well, I suppose anything that anything that reduces morbidity technically in one for I mean people that make helmet bike helmets are longevity companies. You know, >> you're right. And it's 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 dissue. come up with something sexy. Hubman says he thinks retatride will be a trillion dollar drug. What do you reckon about that? >> Um I think it's possible uh if the oral ones really look good that they may actually be uh even more interesting. But yeah, what is it something like 10% of Americans have either tried it or been on these drugs or >> I think 45% of Americans say that they would. Jerry, can you uh chat GPT whatever the the numbers are of GLP users and desired uh users in the USA to find that out. Uh but yeah, I mean what is it? Obesity is twice as big of an issue as malnut as a as starvation now globally. A 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 a GLP 15%. So that means that only what's that about 2/3 of people who have used one are currently using one and 9% of Americans are aware of them. uh 20% of US households. Can you say uh how many people want to uh I'm sure that this was from uh 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. Yeah, I will say that my number is correct. Cool. That sounds great. Um, >> yeah, I I mean the off target effects of this Oh, it seems like people don't want to drink alcohol so much, though. It seems their cravings for video games and porn get cailed sometimes. I mean, I we're getting into not just like 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 Gogggins 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, right? On both sides of it, whether it's good or bad and okay, well, maybe I'm going to get up on time. You know, I didn't eat the junk food last night. I'm on a bit of a roll. Yeah, maybe it was pharmac pharmacologically uh assisted with what I did with my discipline around food, but I'm getting up or maybe there is some, you know, super magic wizardry that's going on inside of the brain. I don't know. But it's definitely interesting. And [ __ ] like it does feel the one 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. >> Yeah. >> Um but it's a blessing that that obesity was 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 GP1s 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 at in 50 years time? Uh yeah, I think that uh eating three meals and snacking that this you go to the you go to the supermarket and there's health bars down the whole aisle aisle that you're supposed to never be hungry. That's going to be seen as extremely toxic. You you your body needs to feel hungry sometimes. Uh have a break from food. So this this trend of you're a bad parent if your child feels hunger is going to be looked at like oh what were we doing to our kids? >> Mhm. >> Do you think AI is going to make bigger inroads into longevity research? I don't know what. I mean again you know 7 years ago when we sat down AI you with your snail your drawing of a [ __ ] snail on the whiteboard. There was no AI to be found. >> I don't remember what the snail was dude. 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 we we said Chris is coming. Let's draw a snail through. >> Draw a [ __ ] snail. He's the idiot British guy. We'll get him in and he'll be convinced that it's actually something really important. What's AI 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 160 years. And that was like that's using old technology. These days we can do I'll tell you I 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 3 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 uh 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 do that thinking you know how that'll take the next 5 years >> exactly because I've had about three people in my lab try to do that and they were not really successful >> and and he came in on Friday uh and he's with his team and his mentors and we sat in my office and they've all got this big grin 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 and we got some graphs. This was truly using AI. He was using one of the the 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 cuz 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, "Uh, 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 amazing. >> Love the idea." [ __ ] branding. >> Yeah, we'll work on branding later, but the fact that you found it is incredible. And that's a 19-year-old uh I think 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 wild. So, have you has there been anything as far as you're aware in the field of longevity that's been uh generated or inspired by AI that has gotten itself to trials, testing and and fully published as a world change or is are we still at the frontier of that not reading meeting the real world yet? H >> we we're undergoing this revolution. So tomorrow is 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 >> uh and hundreds of millions of dollars. It's that world. We can go from now that um uh Demis Havis 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 cuz they used to be one-dimensional based on the DNA. Now we got threedimensional 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 silicico 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. 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 onetoone 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. Okay, maybe this you can discount a lot and then the interesting ones get moved into the real world. >> Yeah. Yeah. And 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 384 little wells. And each one has a different chemical that's 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. You know, this kind of work is is 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 [ __ ] primitive. >> And now we can do that experiment with hundreds instead of trillions. And trillions is impossible, by the way. Um, the most a pharmaceutical company would screen would be in the millions. Now we do trillions. Uh, 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. Um, and then I thought, oh, 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 90year-old cells, 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 uh month or so, give it 2 months, we will have a set of chemicals that can replace the current cocktail that reverses aging in the mouse. that if you were 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 um 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 drug or a patch >> or a thermal thing >> and some 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 uh we'll run from there. >> How big of a role is expectation in how someone lives? If somebody thinks about aging as being associated with frailty and degeneration, can that actually make them live less long? >> Oh, you mean mentally? If they're Yeah, that's wellstudied. If you're optimistic and you're enjoying life and you don't just get retired, just retire and be bored. Um, yeah, mental attitude is huge. Um, Robert Valdinger, a Harvard scientist, has found that the mental attitude and your social life is as important as your blood pressure and cholesterol, if not more important. And the one thing that was the best was have a reliable partner. I went through a divorce. It was horrific during co and I believe that it took years off my life. So, it felt like it anyway, but uh it was it was a shock. I didn't know it was coming, but uh it's brutal. Um, anyone that is young getting married, just beware. Um, we all change over decades. So, that's a something to keep in mind. But the point there is, uh, the amount of stress and cortisol that runs through your body when you have a really big life event, moving house, breakups, uh, 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. um the exercise, the diet, the social life, the sleep, the relaxation. These are all we know um are likely to not just slow aging, but eventually keep you disease free. And I do 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 being 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 uh uh women that he's excited about. Um no, they're good friends. I won't I don't want to disparage my father. He's not a dirty man, but um he he is a very sociable guy. and in his 40s he was raising me and I wasn't easier to raise. I was a pain in the butt. He will 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? >> Um definitely don't overeat. Be lean. Watch your weight. Have a BMI of around, let's say, 22 24. Make sure you you don't get overweight. Um obviously don't overdrink and don't smoke. These are clearly really the worst things you can do having lost a mother to smoking. Um so don't eat too much, right? Try to skip meals. Uh work out, maintain a very good body mass, um and exercise. Those are the fundamentals. Everyone will tell you that. Um 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. Um they taste meat tastes great. But I've 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 um that took me a long time to to learn that as well. But I've never been healthier because I've it's been slow, but I've learned how to do all these things really well. >> I'm going to do a lightning round. So in a sentence or two, give me your review on these interventions for longevity. Okay. Okay, >> creatine. >> We doing how we how we scoring? >> Just however you want. You 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. Um, in favor of it, and take it. >> Stem cells. >> Interesting. And if you have a certain condition like a a joint that needs repair, can be helpful, but it's not long-term solution. CPAT machine >> really important um for folks that have anoxia, lack oxygen at night for the brain. Um though you could try other methods which is lose weight um don't drink uh get a thin pillow try to sleep on your stomach. hyperbaric oxygen therapy >> uh in favor. There's good evidence that certainly cycling uh up and down in pressure is good for the brain and blood flow and have done it myself and uh have seen improvements in wound healing in others. So yeah, in general it's it's a plus. >> Blue light glasses. >> Yeah. You you mean yellow uh blue light blocking glasses? Um, 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 5 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 uh and you're a mouse, you get uh short-sidedness. So early morning light can be uh protective like for your eyes. >> Yeah. Yeah. And we live indoors and we we don't get enough of it from LEDs. >> Okay. Glucose monitors. >> Love them. They're really good. Yeah. I I I think that we should all be empowered by our own data. Um 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 grape thing you sign. >> 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 uh have the best blood glucose levels. And he would eat a lot of bad stuff. It changed his life. He's 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, as I think you mentioned earlier today, can really really make a difference. >> Therapy? >> You mean just general uh psychology? >> Psychotherapy. >> Well, I think it depends on the person and the therapist. Um, I think that talking about your problems can really help. Um, I think it can be overused. Um, as a friend, um, I've I've tried everything. Um, I didn't find a lot of the therapists to be that useful. I found it better to read books and listen to experts and um, but I do think therapy is very important. I've um, had kids that benefited from therapy. It's very hard being a teenager these days uh, with the pressures. So, yeah, a thumbs up for therapy though. Make sure you have a therapist that is wellqualified and provides benefits rather than just listens to your complaints. >> Grounding? >> What do you mean >> grounding? Walking on grass, negative electric discharge. >> I don't think that's scientifically based, but I do think getting out in nature and touching uh nature, smelling nature, listening to nature is very valuable. and our body will turn out to respond in ways that we don't even understand yet. >> Marriage, >> be careful who you marry. Um, know that it's not always forever. Know that people change over decades. Um, 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 uh mouth taping. Uh so I I do snore if I uh have a thick pillow or eat certain supplements at night, I found. So I have tried mouth taping and Serena says I make even more noises gasping. So I don't use mouth tape. I I do use those nose strips cuz she thinks they help. >> Y >> but no, I haven't had success myself with mouth taping. >> Testosterone therapy. >> Uh I prefer natural versions. If you can't raise it naturally, yeah, for older people, there's been a lot of benefits. Um I mentioned Shellyley Basin as a scientist that's worked on Nammen. 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 you talked a lot today about supplements, lifestyle interventions, rest recovery, what the future's going to look like, AI, GLPs, something that we never got to talk about when me me and you first sat down with the perils of overoptimization. I think that it was so frontier in 2019. Everything was new and exciting and you couldn't really be drowning in data in the same way as you can now. Mhm. >> 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 is possible and also dilitterious to health. Uh, so if you have those tendencies, be careful. You know, it's true for anything. Social media use as well. Um, and I I can be obsessed. What what I've done myself, which I recommend, is treat it like a hobby. It's fun. It's not too serious. You're not going to die if you didn't sleep well last night. Um, and you know, everything's challenge. Uh my meals are an experiment. Um not always. Sometimes it's a failed experiment. Um but I live my life like it's a journey and it's fun and I'm testing things. Um 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. Don't stress. >> Heck yeah. David Sinclair, 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? >> Uh, 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. Um, and I'm on social media. You can see what I do. >> Podcast season. >> Podcast is big. Uh, so that's on YouTube and all all podcast. Uh, that's called Lifespan with Dr. David Sinclair. We have we're building. We're about half a million followers. is not like you, but we'll get there. >> You're doing good. >> We did take some time off to do the trials, but we're back and uh even better now. So, join us there, too. Thank you, Chris. >> Appreciate you, mate. >> Likewise. >> Till next time. All right. Goodbye, my beauties. >> Dude, yes. So good. Congratulations. You made it to the end of a podcast episode without dying. Now, here's another one. Go on, watch it.