스크립트
00:00:00The first ever podcast episode that I recorded in America was with you in 2019, Harvard Medical
00:00:08School in your office with what looked like the illustration of a snail on the whiteboard.
00:00:14And it was filmed on two iPhones, one of which I'd had to borrow from a friend and a single white
00:00:19USB microphone. And that was over seven years ago. And now here we are.
00:00:24I remember it well when you were 12, right?
00:00:26I was 12. Yeah, correct.
00:00:28Yeah, it was very clear from those days that you were going to be a big success,
00:00:32smart, driven, came prepared. And look, this is beautiful now.
00:00:37Full circle. Yeah, I didn't realize Starbucks Venti has way more caffeine in than the British
00:00:46equivalent. And it took my fucking face off. I was sat opposite you trying to think about
00:00:50Yamanaka factors and how important NAD and resveratrol in yogurt is. Meanwhile,
00:00:55my whole body was vibrating, but you've done maybe more than almost anyone to make the biology of
00:01:02reversing aging a part of mainstream conversation. So I want to talk about kind of everything that's
00:01:08happened since we first sat down, the Yamanaka factors, what's happening with NAD and resveratrol,
00:01:14new discoveries. Before we get into that though, what discoveries have excited you most since 2019?
00:01:22Gee, a lot. I'm very lucky to have a lab where there's up to 40 people
00:01:30running around making discoveries. I go back there to recharge. It's like the Willy Wonka.
00:01:35You've been there, so you know what it's like. It's unparalleled. I wish everyone could come visit.
00:01:41The highlights would be, so in 2020, we published on the cover of Nature magazine that we could reverse
00:01:48aging safely in an animal for the first time, a mouse. We cured its blindness. That was pretty big.
00:01:55Cover of Nature, it's what most scientists dream of in their lifetime. So that was a pretty big high.
00:02:00Since then, it's been rewarding to see that it's been repeated, not just by other labs, but in different
00:02:07animals, monkeys. It's been working in different tissues. So it's not just the eye anymore where we
00:02:14first tested it. It's pretty much working in every part of the animal's body. And then the big thing is
00:02:20we've now gone into people. So there are people getting their, hopefully, their age reversed in
00:02:26their eye to cure their blindness, or at least improve their vision at the very least.
00:02:31Why start in the eye?
00:02:33Yeah, good question. This is a gene therapy. So we're introducing genes that are very powerful.
00:02:39They're called Yamanaka factors. You mentioned them. But we use a subset of them that don't cause any
00:02:45trouble. If you just use what Professor Yamanaka used, it's not going to be very healthy. It's
00:02:49it's actually quite dangerous. So we use a subset of those and we deliver them with a little virus-like
00:02:55particle. And the safest way to deliver a virus-like particle into a human is to go into a space that's
00:03:02enclosed. It's not going to spread. And the eye is where it's most been tested. And so we did it for
00:03:09safety reasons, not because it would work better in the eye. In fact, I told my student at the time,
00:03:14Won Cheng, that he was crazy to try to cure blindness. Why not do something easy like the liver?
00:03:19But he said, you know, the eye is probably the best place to start for safety reasons. And he was right.
00:03:24I remember that though. We were talking about that in 2019 when I was in your lab.
00:03:33There's been this recent release that came out last month. What's that? Why is that so special?
00:03:39The one about that we've gone into humans? Well, I think most people thought the aging
00:03:46field was a lot further behind. Age reversal you see online. Oh, we've done this in human cells.
00:03:53We've done it in a mouse. But suddenly there are people now getting what could be the world's first
00:03:58true age reversal drug. So for us, it was old news. We'd been doing this and expecting it for a while.
00:04:04In fact, we made the discovery back in 2016, 17. So for us, it wasn't so amazing. But for the world,
00:04:14I think it was a shock to hear that people are actually getting this potentially age reversal
00:04:18drug for the first time. What would be the issue that somebody has in their eye,
00:04:21which would be reversed? What's the sort of patient that this would face?
00:04:24So this is the thing that makes me super excited is that every piece of or type of damage and disease
00:04:32that's been tested in animals, not just mice, but larger animals, it's worked to improve the vision
00:04:42of either a disease or damage. So for instance, if you pinch the nerve, you laser it, or you give a
00:04:50mouse glaucoma pressure in the eye, we can treat that effectively. And nothing reverses blindness
00:04:56currently except for this treatment in animals even. And so that's what's exciting. Even macular
00:05:01degeneration, glaucoma, the two leading causes of blindness in the world, both of them are really,
00:05:07really easily treated by this new mechanism. We call the drug ER100, which is epigenetic reversal 100.
00:05:15But yeah, pretty much any disease or injury could theoretically be fixed, treated by this technology.
00:05:25Theoretically, any disease or injury could be treated by this?
00:05:28Well, in the eye, but even beyond that, the liver, murder neurons, so ALS, the brain has been
00:05:36reversed in aging, memory comes back, even joints. There was a Chinese study that came out recently,
00:05:42looked very good. They used our technology to rebuild bone and cartilage in osteoarthritis.
00:05:49And so, you know, I don't know anything else that just rebuilds body parts like this.
00:05:53Can you explain how it works to a simpleton?
00:05:57Not you, but I don't think anybody listening is a simpleton, but it's actually quite simple,
00:06:02the good news. We take three genes that are normally turned on early in life,
00:06:08and these three genes make factors that turn on a cascade of events that the cell uses to reboot itself.
00:06:18The simple way to think of it is that I hypothesize that the body has software that gets corrupted as we
00:06:24get older. So an old person still has information there, it's just that it's been corrupted, the software.
00:06:32We call that the epigenome. It's separate from the genome, which is the DNA. The epigenome sits on
00:06:37top of that and controls the DNA. So in my book Lifespan, it's a little dated now, but you might
00:06:43remember I chose a CD as the analogy. The epigenome is the reader of the music and the DNA is the music
00:06:50itself. And aging is a scratch CD. So for those listeners and viewers who don't really know what a CD is,
00:06:57they're really cool things we could put 20 songs on. But a better analogy now would be your phone has
00:07:03software. A really old phone is slow, it can be corrupted, can get overused. And so we can reboot
00:07:12that. And we found that these three genes that we put in, which we call O, S, and K for short,
00:07:17these Yamanaka genes, trigger a program that embryos normally use to reset their age, or something very
00:07:23similar to that program. Something you might not know, most people don't know this, is that when
00:07:28we're fertilized, and we've all been fertilized, we wouldn't exist. And then we need to reset this
00:07:33epigenome, the software needs a reset to go back to being young again. And that happens-
00:07:38No way.
00:07:38It's a fact, it's shocking, but true. Young, very young embryos are old, and then they get reset.
00:07:46So the software is really, it's not software, it's the way the DNA is folded in the cell,
00:07:51and every cell has to compact the DNA, because it's six feet long, has to fit into a microscopic little
00:07:56ball. And how that's compacted depends on what kind of cell you're going to get. So if you want
00:08:02to make a nerve cell, you compact different genes. And when you compact them, they switch off. But you
00:08:09need to read nerves that make nerve cells, so you open those up. And this bundling and opening of DNA
00:08:15is what the epigenome does. And my theory, called the information theory of aging, said
00:08:20that this pattern of bundle, loop, bundle, loop, which is different for every cell type, gets corrupted,
00:08:26gets eroded during aging. And that literally is aging. And we tested this and published it in 2023,
00:08:35and we created a mouse where we could disrupt those loops and bundles. And the mouse's cells lost their
00:08:41function, they lost their identity, the nerve cells forgot how to be nerve cells. And the mouse literally
00:08:45got old, we could speed up that process by corrupting that software, the epigenetic software. And then when
00:08:50we did that, which took us 13 years, we started working on reversing that process, which is how we get to here.
00:08:57People see aging as a certainty, but you call it a disease. Is it truly a disease, or is that just a
00:09:04useful metaphor? Well, it's just a word, really. So we can call aging whatever we want. But I prefer
00:09:09to think of aging as a disease, because otherwise, we're not really treating it. Most doctors don't
00:09:16think of old age as something that is preventable or treatable, even though now we believe we understand
00:09:22that it is very treatable, or at least slowable. So I think it's a useful way to look at aging as
00:09:29something that we should address, even starting early in life, to try to slow it down at least.
00:09:35We all need to stick around for longer, because the technology that's coming is incredible.
00:09:39And I proposed this in my book, and even put it on the back cover. And it was,
00:09:45a lot of people were telling me that that's crazy. "Don't say that, David. It's going to be scandalous.
00:09:50People are going to not take you seriously as a scientist." But I'm glad Matt, my co-author,
00:09:56Matt LaPlante, convinced me we should go for it. Actually, that was his main role besides writing,
00:10:02was to say, "David, just do it, because don't worry what your colleagues will say, because some of them
00:10:06can be pretty brutal." So we put it in there, and it's seemingly been embraced by a lot of people,
00:10:13and now you hear it quite often. What's the technology that's coming?
00:10:16If that's what we've done so far, what did the next few years have in store for us?
00:10:21Well, there's a fork in the road. I don't know when it's coming, but it's similar to the singularity
00:10:27with AI or AGI. When we show, and it's a matter of when, not if, that aging is reversible in humans,
00:10:38because it works in all these other animals, it'll work in us. We're basically just
00:10:42slightly more intelligent monkeys, and it works fine in the monkeys.
00:10:47That's going to be a turning point, I believe, for humanity. There'll be a lot of people who say,
00:10:51"All right, now let's get on board. Let's invest. Let's blow this out of the water." There's already
00:10:56a lot of billions of dollars put into this, but it's going to be big like AI when that happens.
00:11:02But these technologies, let's say it works in the eye, and now we can treat, perhaps cure,
00:11:08most types of blindness. Then we're going to, we're already doing this. I should, you know,
00:11:13I can't talk about too much, but we're already looking at other tissues, the liver, for example,
00:11:18and maybe there's joints and hearing that we can also repair. Ultimately, where this is going,
00:11:23obviously, is whole body reset. We can do this in mice easily in my lab now, and others have done this.
00:11:30Every cell in a single organism?
00:11:33Well, we don't have the technology with the viruses and the genes to reset every cell,
00:11:39and that's a limitation of getting the genes into every cell. We can't do that.
00:11:42We can basically, at best, get it into half of the cells, but still a lot of them.
00:11:49We've taken a path that's a little different now. I was saying we've been doing this for a while,
00:11:55and the world doesn't really know what we're up to in my lab.
00:11:58I can reveal that over the last five years, we've made breakthroughs in turning it into a pill.
00:12:04That's the next big thing that'll come out of my lab, is revealing that we can give a mouse,
00:12:09an old mouse, something orally, so they don't chew on the pill. We give it down their throat for
00:12:15three days a week, for a month, and we see that they are rejuvenated in many ways,
00:12:20including not just their memory, but things like even their skin quality.
00:12:25What's happening? What's the pill doing to them?
00:12:28Well, that's a lot of work. We're still trying to figure that out.
00:12:31So you know it works, but you don't necessarily know why or how it works?
00:12:34Well, we actually literally don't know how the genes that are in the eye of humans now work,
00:12:40really. That's a big question in my lab. I was trying to answer, where is this backup copy of
00:12:45software? But we do know it works. That's the hard part. And then figuring out how it works will
00:12:51be important to make these drugs even better and more powerful and more potent and longer lasting.
00:12:56But what we do know is that the epigenome is involved in the pill,
00:13:00not just in the gene therapy, because we can disrupt that polishing of the CD or the reset of the
00:13:06software. There are genes called TETs, which make proteins that strip away chemicals off DNA.
00:13:14These are key to the epigenome reset in embryos as well as in our bodies. And we can get rid of them
00:13:22or inhibit them with a chemical. And we can feed those to the mice or give it to the cells. And we have some
00:13:28good evidence. I hope my students don't kill me for saying this publicly, but we do have good evidence
00:13:34that the pill, let's call it the cocktail, does work through this epigenetic thing. It's not just all
00:13:42the cells are getting stressed out by the chemicals and they fight back and they live longer. It's not
00:13:47that. It's truly through this reset mechanism. And we can show that by getting rid of these TET enzymes that
00:13:53strip chemicals off the DNA. And without that mechanism, the cells don't get younger,
00:13:59even with the chemicals.
00:14:00- Do you think there's going to be a realistic upper bound to human life?
00:14:03- Well, the question is when. I think that ultimately there is no upper limit to human
00:14:09life. I just visited a bonsai garden in Japan where the trees are a thousand years old and they're not
00:14:15even halfway through their life. So biology doesn't have limits. It's just a question of what our genome
00:14:20encodes and our epigenome. But we have control this century over our own biology. We don't have to just
00:14:26be at the whim of what evolution and the Serengeti gave us. And I see no upper limit. Doesn't mean I
00:14:33think you and I will be immortals. That's right now beyond our imagination. Well, it's definitely
00:14:40imagination, but it's beyond technology that I can think of. But I do think that some of us will have
00:14:46a chance to live decades longer and probably the first person to live to 150 is already alive.
00:14:52- First person to live to 150 is already alive.
00:14:56- Yeah. I'm not the only one in my field saying that. It's now realistic. I mean, think about it
00:15:02this way. It's hard to imagine the future, right? But a kid born today is going to live into the 22nd
00:15:08century. And we can't even imagine what the world's going to be like 10 years from now.
00:15:13So the longer you live, actually, the longer you get to live.
00:15:16- Surely if someone took age reversal pills for long enough, they'd just become a baby.
00:15:20- Is that not the way it works? - Well, we made sure that wouldn't happen.
00:15:24That was one of the things that Wan Cheng might- - Benjamin brought everybody into an embryonic death.
00:15:30- Yeah. Well, that was the trick. Professor Yamanaka won the Nobel Prize
00:15:34for making cells go back to age zero and making them into stem cells.
00:15:38But that's not going to help us. We don't want to strip away the identity of all our cells. We die
00:15:43within a couple of days. And in fact, if you do that to an animal, it tragically does die or gets cancer.
00:15:49So what took us the longest time from 2014 to 2017 was figuring out how to reverse aging,
00:15:56but not so much that it loses the identity of the cell, or erases it. And my student,
00:16:04Wan Cheng, famously almost quit the project. He was doing his PhD, he was in his last year,
00:16:10and nothing was working. He was either having no effect on the human cells in the dish,
00:16:15or they would be becoming cancerous. And he said, "David, I don't know how to stop it halfway."
00:16:21And we came up with one last experiment that, thank goodness it works, because we wouldn't be talking
00:16:25about it now. We tried a subset, just three of the Yamanaka genes, and leaving one of these Yamanaka
00:16:33genes out was key. Without that final gene, it's called CMYK, we call it M. Without M, the M gene, cells don't go back
00:16:42100%. They go back about 75 and stop. And that was the breakthrough. The stop was really hard to find.
00:16:49But it's there.
00:16:50Or else you just turn everything into stem cells.
00:16:52Yeah, yeah. Or cancer. It's even worse. Well, maybe not worse, but it's definitely bad. You're not going to live
00:16:58longer or cure blindness. But that was a breakthrough. And Wan Cheng sent me the pictures of the cells that
00:17:04were younger and said, "Eureka, I think we've done it." And it was a remarkable thing to witness.
00:17:09What do you think most longevity experts secretly believe, but can't prove or won't say publicly at the moment?
00:17:17Gosh, that's a good question. I was going to say most of them secretly think that I hype this stuff way more than I should,
00:17:24which is, again, not a fairer thing because my lab is eight years ahead of what we've published.
00:17:30But I think most aging researchers, I can say for a fact behind the scenes,
00:17:35say, "This is going to be much bigger and more powerful than we expected."
00:17:40I've been told by some of my colleagues, "Don't say that number 150. It makes us look bad."
00:17:46And I'll say, "Well, do you believe in it?" Yeah, but we can't say that because we're scientists and
00:17:50we'll lose credibility. So yeah, I think a lot of the scientists are very cautious by nature,
00:17:56by the profession. I'm considered an outlier speaking my mind and what I believe in,
00:18:01but most scientists don't because it's not something scientists typically do.
00:18:06Hmm. Why is it that you're seen as an outsider? Are you throwing more caution to the wind than other
00:18:16people? Is it that their criteria for evidence is different to yours? Is it that your lab has got
00:18:23access to information that other people don't? Well, there's a few reasons. It's definitely that
00:18:28my lab has information that nobody else knows. And that's been difficult my whole career knowing that
00:18:35something's true, but it's not published yet. So in the minds of my colleagues, it doesn't exist yet.
00:18:40And in fact, my book came out in some cases years before we published the work. So the public knew
00:18:46my lab's work before other colleagues had seen it. That's also rare. Another reason why
00:18:53I'm a bit of an outsider is I'm not doing this to be a scientist. I'm doing this because I'm on a mission
00:19:01and my life is irrelevant. I would literally die to achieve this mission. And so, you know,
00:19:07if I get criticized or if I speak my mind, I really don't care. What's the mission?
00:19:13To impact in a positive way, as many lives as possible. This was since I was four years old,
00:19:20my grandmother gave that mission to me because she lived through World War II and the aftermath in
00:19:25Europe. And she told me the horrific things that humans did and can do. And she was always saying,
00:19:33we can do better as a species. And I feel like I want to die knowing that I've done the most for
00:19:39humanity that I could possibly do. And if it upsets a few people, I don't care.
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00:20:40Longevity is a huge field, right? It includes everything. When you think about all of the
00:20:45different types of interventions that people can do, how do you chunk them into groups?
00:20:49Sort of what are the buckets that people should be thinking about as contributing to their lifespan?
00:20:55Yeah. So I talk about this on my YouTube as well. So there's a lot of detail on there now and I've
00:20:59relaunched it. Congratulations. Welcome back into the fray. I'm glad that you've stopped doing the
00:21:03wasteful work in your lab and gone into the serious work of YouTube videos.
00:21:07Yeah. I was working on solving aging and now that the clinical trials have started, I'm
00:21:12back to more important things. But yeah, so what we talk about on the podcast is what are the major
00:21:18things that people can do to slow down aging and even reverse aspects of it.
00:21:22But if we've got this technology coming soon, you're eight years ahead, everybody is doing the
00:21:27longevity escape velocity bet, right? For every day that I live, there's more days that I can hopefully
00:21:32live. So in the interim, those are the buckets, right? That's the stuff that people need to focus on now.
00:21:36For sure. I think anyone that doesn't focus on their longevity might miss the boat. It'd be
00:21:43tragic if you died a few days before some of these technologies came out. And I'm not worried about
00:21:50you keeling over anytime soon. You're very fit. But your parents, your grandparents, think about them. So try to
00:21:55encourage them to live the healthy lifestyle that we're going to discuss now. The buckets are lifestyle.
00:22:03So within that, there's the obvious things that we can talk about, which is what you eat, how you move,
00:22:09how you rest, your stress, these kinds of things. That's what you can do and you should do on a daily
00:22:14basis. It's what I do. Then there's drugs, which some of which may work. So that's metformin,
00:22:21rapamycin, some senolytics, and probably GLP-1 receptor agonists would fall into that bucket.
00:22:29And then there's supplements, which is the Wild West. There's a lot of things said about them.
00:22:34I believe in a few of them based on a lot of animal research and some human data.
00:22:38Those are the three main things that you should do in your daily life to maximize your chance of
00:22:43getting these medicines. Okay. Lifestyle stuff. Last time that we were talking,
00:22:48it was all about calorie restriction and primarily fasting as a route toward calorie restriction.
00:22:56How should people eat if they want to live as long as possible now with your 2026 data?
00:23:00Well, actually what I've been saying, actually on my podcast for now, what, four years? It hasn't
00:23:07changed. And my book, Lifespan, which came out, we were talking about when we first met in 2019,
00:23:12nothing in that book I've had to revise. It's all consistent.
00:23:16So there's no retractions from the book in 2019?
00:23:18No, no. And my lab's never retracted anything. And at this point, never been proven wrong,
00:23:22which is a blessing. And I knock on touch on wood, but that's good news, which means that the things
00:23:28that I've said before, people can go back and learn still. If this is the first time you're seeing me,
00:23:34you know, let's, let's start. So the main things about fasting are, we know from animals and some human
00:23:42data, but mostly from animals that if you restrict how often you eat, um, and to some extent, how much
00:23:47you eat, you get longevity benefits. Um, and we can talk about protein ratio to carbs, to fats.
00:23:55That's also a whole big debate, as you know, but generally I, I like to eat one meal a day,
00:24:01maybe two if I'm being social, but not three, I think three meals a day plus snacks is marketing.
00:24:07Um, breakfast being the most important meal of the day was general meals. I believe, uh, one of
00:24:12those companies Kellogg's perhaps, but, uh, this is, you know, it's all marketing. Humans are not built
00:24:18to eat that consistently. I don't think cavemen were sitting around eating their big breakfast
00:24:23saying, what are we going to eat for lunch? I think, you know, maybe if they just killed a mammoth, but
00:24:28generally they were pretty hungry a lot of the time. And our bodies have adapted to that. We're
00:24:32not meant to always be satisfied. Um, and so I try to be hungry. And if I gain a little bit of weight,
00:24:38sometimes I travel and I eat well, and Serena and I, uh, we do sometimes love to eat. I'll come home
00:24:45from travel and just, I won't eat for three days. Sometimes two weeks I can go without food. It's not a big
00:24:51deal for me. Two weeks without food. Yeah. Okay. I might munch on a, on a piece of celery or something,
00:24:57but that's not really nutrition. I will drink a lot. I'll drink a lot of low calorie, zero calorie
00:25:04drinks, a lot of tea, that kind of stuff, but I can go without food for two weeks. It feels great.
00:25:08After the first three days, I'm over the hunger feeling. Um, I can see on my monitor, which I've
00:25:14got one on here. CGM. Oh, the CGM. Yep. Uh, I can see the great impact it's had having on my body.
00:25:21I can monitor it on my rings. I do blood tests, which is important. You don't want to just guess
00:25:26what's working, what isn't, but yeah, I know two weeks sounds like a lot, but it is a lot.
00:25:31It's like, it doesn't sound like a lot. It is a lot. It is a lot. And I'm a regular guy. I, I, I, I'm not
00:25:37like some people that spend millions of dollars on their body and, and measure everything. I'm kind of
00:25:41lazy. I, I don't like being hungry. I like food. I like to snack. I like to stay up late. I'm a typical
00:25:48hedonist. If you let me go. Um, and actually up until a year ago, I actually hadn't fasted more
00:25:54than 24 hours. I just couldn't do it. It's like, this is painful. Um, and I'm stressed. So if I'm
00:26:00stressed, I'm going to eat. Um, but what I've learned over this past year is I can go beyond 24
00:26:05hours. And once I'm over three days, something kicks in. Actually, we know, molecularly,
00:26:09there's something called chaperone mediated autophagy or CMA, which is the deep cleanse of these
00:26:15misfolded and modified proteins that you want to get rid of for aging or slowing aging. And, uh,
00:26:20after those three days, you know, I start to feel amazing. My mind clears. Um, I don't feel bloated at
00:26:27all. Um, I don't even have to go to the toilet that often except for all the tea, but you know what I
00:26:32mean? And, uh, yeah, I feel energized and I, I'm measuring myself. So I'm making sure I'm not overdoing
00:26:38it. This is not for everybody. If you're skinny and you've got barely any fat or you're elderly,
00:26:43it's not for you. But for me, I gain weight and muscle pretty easily. I can fluctuate. And so I
00:26:48watch my weight come down. I've got, uh, a scale that measures my weight. Um, it's, I don't know if I
00:26:54can measure it, say the name or if it's forbidden, but, um, I do like the Withings scale.
00:27:00Cause smart scale links to the phone. Yeah. We get your composition as well. If you hold the handle.
00:27:04Yeah. And I've had one since 2013. So I've got all this data on my body weight and composition,
00:27:09which is awesome. And I'm trying to maintain that at the optimal level over these last 13 years.
00:27:14What do you, this two weeks things blow in my mind. What are you running on
00:27:18after 10 days? So you, why is malnutrition? Are you supplementing with,
00:27:21with vitamins and stuff so that you don't get scurvy? Like why are you not dropping dead?
00:27:25I am. I'm glad you said that, Chris, cause it's important to say
00:27:29I'm a scientist about this. I'm not just willy nilly giving up everything.
00:27:32So you celery and green tea surviving for two weeks, just bro-sciencing it.
00:27:35Yeah. Well, no, I'm not doing that. I, uh,
00:27:38the reason I'm using my hands is I travel and at home, I have a little carry pack with vitamins,
00:27:44supplements, um, and medicines that I've been using and know very well what I need. I, every morning,
00:27:50it's a symphony of supplements and medicines. Actually, I know what my body needs. I know what,
00:27:54what works. Uh, so I do that. So there's not, not anybody can do that. So it's really important.
00:27:59If you do fast for long periods, make sure you enough hydration, very important. We know that,
00:28:04but also I'm making sure that I'm not deficient in any minerals or vitamins. And so I'm, I'm taking
00:28:09in things like vitamin B, uh, vitamin C as well, and some nutrients that I know I can become deficient in.
00:28:17What do you think is happening inside of your body after from day four until in the day 14? What's,
00:28:24what's going on? Well, we, we know actually, um, not from measuring me, but we know from many years
00:28:31of study, what happens to the human body, uh, the first 24 hours, you're going to, uh, use up a lot of
00:28:38the, the sugar and then the glycogen in your liver. What I like to think is my liver knows how to
00:28:45steady my glucose and give me the right amount of glucose far more than my mouth does.
00:28:49I live as smarter than my eyes and my mouth. And anyone that's fasted knows that your blood sugar,
00:28:54if you're eating like this and you go, Oh, energy, Oh, brain fog, energy, brain fog. Oh,
00:28:59I'm sleepy in the afternoon. That's our normal life. If you're fasting, your liver just puts out
00:29:04just the right amount of ketones for your brain. Um, or you can drink some, some ketone drinks,
00:29:09um, or, uh, it's making glucose or both your brain is loves ketones. And, uh, if you do it too long,
00:29:18you will start to lose muscle. So I'm working out more than I do normally to make sure I don't
00:29:23lose any weight. And so that scale will tell me if I'm losing lean mass, which I don't want to do.
00:29:28And I make sure that I don't lose it. Is there not a concern to do with your gut?
00:29:34Is there not, is that, does there not need to be transit through the digestive tract?
00:29:39I don't know what happens if nothing passes through your stomach for two weeks.
00:29:42Yeah. Well, I can tell you your stool changes, uh, there's very little.
00:29:45I imagine it does. It turns fucking invisible.
00:29:47Yeah. Right.
00:29:48There's phantom poo.
00:29:49There's just a bunch of gas coming out. Um, so yeah, that's what I meant. I'm not on the,
00:29:54in the bathroom as often. It's actually much more productive, um, unless you're productive.
00:29:58I do find, I do, I do find that the biggest obstacle to my productivity is the bathroom.
00:30:05Are you sure you're not, you're not tweeting away down there. Uh, but yeah, your microbiome,
00:30:10I think, and, and this is not proven, um, by any means, but I feel like just like your body,
00:30:16it helps to give your microbiome a shakeup, a bit of hormesis, which is a little bit of stress.
00:30:22That's good for you. And, uh, I would love to do an experiment on myself as well, measure before,
00:30:29during and after and see what happens to my microbiome and stuff like that. Well, I mean,
00:30:33I know that some of the proposed positive effects for GLPs include slowing motility through the gut,
00:30:40which actually helps with things like SIBO or candida or H pylori, because the pace, this is why
00:30:47everybody, every bro lifter that's listening to this, you, you at some point in your life have glanced
00:30:53off the bottom of SIBO, or maybe have it right now, because just the sheer volume of food that you're
00:30:58putting through yourself all the time, grazing high protein, high starch. Like that's one of
00:31:04the proposed mechanisms I think that helps from GLPs. And I don't know, that's what, what I was
00:31:08interested, maybe creating this very, I was going to say sterile environment. It's not, it's barren,
00:31:13this completely vacant environment for two weeks. I have no idea what that does. If you had a overgrowth,
00:31:21does it kill it all? Cause it's not being fed. Does it allow it to create castles and cathedrals and,
00:31:26you know, armor itself? Yeah. Yeah. Well, I don't know the answer to that. I, I do know that there's
00:31:32some really interesting things in bile that, uh, comes out more when you're fasted. Uh, one of the
00:31:38components, um, is a type of colic acid, which is the black, black stuff that goes into your microbiome
00:31:46and your microbiome converts that into a molecule. It goes back into a bloodstream and turns on a longevity
00:31:52gene that we've been working on. Uh, it actually binds to the protein and makes the protein more
00:31:56active. It's called SIRT1. If anyone's read my book, they know what SIRT1 is. SIRT1 regulates
00:32:02the epigenome, slows down the changes to the software. And so long story short, it's, it's at least
00:32:09plausible. And there's a nature paper on this from another group that I reviewed that when you're
00:32:13fasting, your microbiome is more actively converting bile into healthy molecules as well as short chain
00:32:20fatty acids. There's a lot of literature on that. And these molecules go into your body and they signal
00:32:26adversity. And you know that I like adversity. Adversity is good for your health. Um, there's
00:32:31abundance and adversity mode. They're both good, but you don't want to stay in one or the other.
00:32:35You'll, you'll accelerate your aging and you'll, you'll die. So you want to cycle between adversity
00:32:41and abundance and your microbes help you get through that.
00:32:48What would you say? Let's say that someone finds this quite seductive.
00:32:53What would be a good start? Uh, one day fast, a three day fast, and what, what should they do?
00:32:59What would be a rough protocol to follow without having to be a conductor of supplements?
00:33:04Yeah. Well, if, if you're, if you've never fasted and you just wake up and you eat a normal breakfast,
00:33:11lunch, dinner, either you're, you're obese or you exercise a lot because that's going to put on weight.
00:33:16Um, but if you are willing to try, I would suggest skipping one meal and replacing it with a lot of
00:33:27liquids. So for me, I, I don't mind skipping breakfast. Not everybody wants to do that because
00:33:33they work out and they feel like they need some food. Um, so you can, instead you can skip dinner.
00:33:38I would just have a very early dinner. Um, what I was doing for many years, probably 30 years of my
00:33:43life was trying not to eat anything until late lunch. Um, and you, you will initially feel hungry.
00:33:49This is the thing. Don't give up because it takes a few days for your body to get used to not having
00:33:54the food. It'll be screaming at your brain. I'm so hungry. I'm going to die if I don't eat this
00:33:59bacon and eggs, uh, but get, get through it. And actually after two weeks, it'll become really
00:34:06weird to eat food in the morning or at night, your body gets used to it, your brain gets used to it,
00:34:11but it does take a while. And the cheat code is fill your stomach with lots of liquids,
00:34:18not sugary drinks, not a lot of, uh, of calories zero, if you can, or just a little bit.
00:34:24Um, I do have a little bit of calories in the morning because it's good with my supplements,
00:34:28but, um, a lot of water. So a low calorie drink like this or water, tea, um, black tea,
00:34:35coffee is very good. They're both good. Actually tea and coffee are both very good for you because
00:34:39they contain other molecules like polyphenols that again, can activate these enzymes that protect us.
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00:35:51Have we seen any data that shows calorie restriction increases lifespan in humans? I know that this
00:35:59exists in rodents. Yes. There was a study that was done, was it macaques or something and that didn't
00:36:06actually work because it was a two decade study. And the first version of the study, it turned out that
00:36:13they hadn't fed them the same diet and split it in half. They'd fed one of them a junk food diet and
00:36:17the other one had been given a healthy one. Then they ran it back and it seemed like the data was
00:36:21mixed there. What's the evidence about calorie restriction for longevity in humans? Is there any?
00:36:25Uh, no, uh, there's a lot of anecdotal and historical evidence that fasting is good for you.
00:36:31And there've been some short-term studies over a couple of years. There was the calorie study
00:36:35that showed that you could improve a lot of health biomarkers in humans over that time
00:36:40that had lasting effects, including on the epigenome, but nobody's really done a prospective
00:36:45study, uh, with placebo. It's very hard to do that or even controls. So there's no proof.
00:36:51And I don't think anytime soon there'll be proof, but who wants to wait another hundred years till that
00:36:55happens? You can't, you've got to at least go based on the evidence and in animals, it's incontrovertible
00:37:01that, that if you do it with nutrition, not just starving, it's very good for you. Um, and that's
00:37:08why I do it. I would say with the monkey study, I know it very well because the two labs that disagreed
00:37:16about this. One, uh, is one of my best friends and the other one is my trainee. And they were,
00:37:23Oh, wow. You're like Switzerland in between the two of them.
00:37:25Yeah. I didn't really get involved. Um, but I did bring them together and they,
00:37:30they came to the conclusion that yes, it did extend lifespan. Um, it depended on
00:37:38the, the veterinary care and other, other environmental things. The university of Wisconsin,
00:37:42where the other lab is, uh, Rosalind Anderson is the professor that I originally trained. What is it?
00:37:4920 years ago, uh, she runs the study now and her monkeys lived longer. And they also definitely
00:37:55incontrovertible, uh, evidence that they had less cancer and I think heart disease, but definitely
00:38:01overall disease burden in these monkeys was lower and they lived slightly longer.
00:38:07But even if they didn't live longer, I would say still look at the data on the diseases. I mean,
00:38:11who wants to get cancer and heart disease in their sixties and seventies?
00:38:15Why would high calorie turnover increase your likelihood of cancer and heart disease?
00:38:22Well, there's a few different theories. The one that I liked the best, that's the simplest,
00:38:26is that when your body is in a state of perceived adversity and running, building muscle, lifting
00:38:33weights and hunger are signs of adversity. Um, also eating plants that are stressed is a sign to your
00:38:39body that your food might run out. This is put your body in adversity mode. And this enzyme that I
00:38:44mentioned earlier called SIRT1, which protects the epigenome, it responds to hunger and exercise.
00:38:50Um, there's a molecule called NAD that a lot of your listeners and viewers would know about.
00:38:55This enzyme responds to NAD levels. Uh, but long story short is when you're in adversity mode,
00:39:01your body switches from growth and reproduction into survival mode. And at least if you do that for
00:39:07some of your day or some of your week, you'll get some protection against the ravages of aging,
00:39:13epigenetic changes, um, DNA damage, all of these things that we know contribute to aging.
00:39:18Do you think that there would be a marked difference between somebody who restricted
00:39:21their calories by 30% over a year, let's say, and somebody who restricted their calories by 30%
00:39:29with big breaks in food? Calorie restriction versus calorie restriction through fasting,
00:39:35do you think that those two people would have different kinds of outcomes?
00:39:37So that one is eating more than the other?
00:39:42No, they're both eating the same amount of calories. Let's say that, let's say that, um,
00:39:46somebody has a hundred calories an hour for 18 hours of the day. And another person has one meal
00:39:52that's 1800 calories per day. Um, there's a lot of evidence that eating within the time window is the
00:39:59one that's much healthier. Um, the friend that I mentioned earlier, Rafa, Rafael de Cabo down at the
00:40:04NIH here in the U S what he did again in mice, but I think there's a lot of evidence that it would
00:40:10translate to humans. He gave mice roughly the same amount of calories, but he gave it to them all day
00:40:17and they had to gobble it all down quickly. It didn't matter what they were eating. It was different
00:40:22amounts of protein, uh, carbohydrate fat. He was hoping to find the optimal diet, but he found that
00:40:28the group that ate within that window lived substantially longer than the ones that ate continuously.
00:40:33I saw you quote tweet something about protein being overhyped, the protein maxing movement. What's
00:40:42your position on that? Yeah. No protein is good. Um, I'm not against protein at all.
00:40:47I ate a lot of protein myself, actually, mostly from plants for reasons that I'll get to, uh,
00:40:52but the, this die hard, be a carnivore, forget about the green stuff is, is definitely not consistent
00:40:59with the science of longevity. It's consistent with the science of bodybuilding and it definitely,
00:41:04which of course we know is a superior science. Yeah. So the science of longevity. Yeah. Well,
00:41:09you know, I, as much as it doesn't look like it, I really like bodybuilding over other exercise.
00:41:14Um, I'm just busy. I used to work out a lot. Um, I love bodybuilding and protein is essential for
00:41:20building muscle. No question. Okay. And you can get a lot of protein from protein supplements and meat
00:41:26where I think it's been overhyped is we know that plants are essential for providing polyphenols and
00:41:35having a lack of branch chain amino acids specifically is also very good for health.
00:41:40A lot of data on that, especially in animals, but some in humans. So branch chain amino acids,
00:41:45some people listening will know what they are. Valine, isoleucine, leucine. These are three of
00:41:51the 20 amino acids that are found in more abundance in animals than in plants. And when you give animals a
00:41:57lot of these branch chain amino acids, uh, they live shorter than if you give them less. And this has been
00:42:02shown in short term studies in humans. If you restrict protein, um, that has a lot of branch chain
00:42:08amino acids in humans, they get better metabolically, but I'm not saying you can't eat meat or you can't
00:42:13eat protein. What I'm saying is just doing one or the other, uh, is not really the best way to live.
00:42:20I think the best way is to pulse it. Okay. So if you're working out, you want to build muscle. Yeah.
00:42:26You can eat, you can eat meat. I eat meat occasionally. It's not a problem, but you want to have a period
00:42:31of your life or your, let's say your day or your week where you're not eating meat or you're just not
00:42:37eating. Um, and that puts your body at least part of the time in this adversity mode.
00:42:42Should you be doing both? Let's say that somebody is doing OMAD or 16-8 or some sort of fasting
00:42:49protocol. Would you still be looking to pulse protein intake as well separately to that?
00:42:55Yeah. I, yes. Yeah. The answer is maybe go one day a week without protein as well.
00:43:00Well, without protein, I don't think you'll live, right? You need some protein, but you'll, you mean
00:43:06huge amounts of protein or you mean meat. I mean, like you're saying that there's time for you to
00:43:11focus on protein and then there's time not to, you should be fasting. I'm wondering whether you
00:43:16should be fasting from protein from a macronutrient standpoint as well, in your opinion.
00:43:19I 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
00:43:27to fast from a lot of animal protein, which has these branched-chain amino acids. And we know the
00:43:32molecular mechanisms. There's mTOR, which anyone who follows longevity will know about this mTOR.
00:43:38And if you're eating a ton of meat every meal or every day, your mTOR is going to be active. And mTOR's
00:43:44role is to help cells divide, grow, build muscle. Great. That's what you want to do when you're young.
00:43:51You want to build muscle. You want to look good. You want to be strong. Even if you're older and
00:43:55you have sarcopenia, mTOR is good. But we know that animals that have active mTOR live shorter than
00:44:00those that have less active mTOR. So how do you get the benefits of both? Well,
00:44:06that's what I'm saying. Have mTOR switch down. Plant protein mainly. Don't eat a lot.
00:44:12mTOR will help you when it's switched off. But you can rev it up when you want to build muscle or
00:44:18run a marathon or something like that. You don't always have to be in one state or the other.
00:44:22Okay. Talking about exercise, has your exercise philosophy changed? What is the best exercise
00:44:28protocol for longevity in your opinion? No, it hasn't changed a lot. I just keep
00:44:33seeing studies that say the same thing over and over again. And then people argue about the latest one.
00:44:40We know that the best health is a combination of weightlifting. Muscle is good for hormones.
00:44:46It's good for not breaking bones when you get older. Balance is important. And then the other one
00:44:52is aerobic VO2 max. We know VO2 max is correlated with very long life. And so you do need to lose your
00:45:00breath minimum three times a week, 10 minutes. It's rare that people talk about sex as a way to exercise.
00:45:09I see your eyes bulging. I'm just waiting to see where you're going to go.
00:45:14Well, I was looking at a tweet the other day at an ex, whatever we call them now. And it was saying,
00:45:20oh, I won't say who it was, but they said, oh, you can lose your breath for 10 minutes three times a week
00:45:27by doing XYZ. And I thought, well, no one ever mentioned sex. So if you have an active sex life,
00:45:34count that as part of your daily longevity routine or your weekly longevity routine.
00:45:38Okay. Sufficiently vigorous sex can be- If you can go for 10 minutes vigorously, that's a good start
00:45:46for longevity. There's sometimes restrictors for that, that aren't simply cardiovascular, but go on.
00:45:54Well, you can supplement it with just running on a treadmill, going outside, rowing, sport,
00:45:59all of this stuff. The way to know if you're exercising enough to build up your VO2 max is
00:46:05you shouldn't be able to carry out a conversation easily like this. You're panting. That's my judge.
00:46:11I need to do a lot more of it. These days, I tend to do a lot of my exercise aerobically,
00:46:16running to catch a plane. I admit that I'm not the perfect role model for exercise,
00:46:22but I do know what the science says. And that is the combination of the weights, the balance,
00:46:28and the aerobics. What about zone two? You haven't mentioned low and slow.
00:46:35Well, if you can't do fast and quick and hit, low and slow is fine. Walk, move, get up. I'm
00:46:43always walking around my office. I have a standing desk. I rarely sit down. So that kind of exercise
00:46:48is very good, certainly for balance, overall metabolism. So yeah, I try not to sit at all.
00:46:55I'm sitting now, but I rarely sit during the day. It's one of the things people find weird about me.
00:47:00They come to my office and I'm pacing, I'm twitching, I'm often chewing gum.
00:47:06That's not the same as zone two though, right?
00:47:07No, no. You need to do a little bit more than that. What I like to do is a sport.
00:47:15Tennis could get you there. I do a lot of gardening, so I'm carrying stuff.
00:47:19Gardening is a sport?
00:47:20Yeah, that's my sport actually. It's my big hobby.
00:47:23Interesting.
00:47:24Lifting a lot of heavy plants and building walls and hammering and drilling and all that stuff.
00:47:31Yeah, a little bit, you know, kayaking is something that I like is good. I'm not out of breath,
00:47:36but I'm getting a good workout.
00:47:38Sleep and recovery and rest. What is the most up to date data saying around that from longevity?
00:47:47It's still the same. You do need to watch your sleep. If you're not getting quality sleep or
00:47:53sleeping for that long, it's going to affect your metabolism. Figure out how much sleep your body
00:47:58needs at a minimum. You can do that using some of these rings. It's very good for that. Some people
00:48:02need eight hours. Some people need seven hours. Typically, if you're younger, you need more.
00:48:07The good thing about getting older is you need less, typically. But it's also about quality.
00:48:12I can get away with five hours sleep, and my HRV is still in the 80s, 90s,
00:48:17because I'm getting deep sleep. I'm not drinking caffeine late in the afternoon.
00:48:22I practice as best I can relaxation, meditation, practices breathing, and that gets me to sleep
00:48:29and into REM and deep sleep pretty quickly. I also take a supplement that my partner Serena makes,
00:48:36and it's got L-theanine and some other stuff that also I know from my own experiments gets me into deep
00:48:43sleep quickly. And so my efficiency is typically, according to these rings, in the 90s, 90 percent,
00:48:49sometimes close to 100. And then I can get away with less, which is nice because I travel a lot.
00:48:54I think that's the big learning that everybody who starts using a wearable takes away from it,
00:48:58which is you're sleeping way less than you think you are. Like, well, you know,
00:49:01I was in bed for eight hours. It's like, no, you thought that you went to bed at 11,
00:49:06but it was actually sort of 11:30, and you were reading or watching TV until nearly 12. And then your
00:49:13actual efficiency was maybe 85 percent. So that seven hours has turned into 5:45 or six or something.
00:49:21And yeah, it's stock. I've got maybe 1,500, maybe 2,000 nights on Woot tracked over the years. And
00:49:31you're just always sleeping less than you think you are. Like, if you don't have money to buy a wearable,
00:49:36just the rule is you're sleeping less than you think you are. That's it.
00:49:38Yeah, I agree. And especially if you're eating late, drinking coffee or tea late, or matcha,
00:49:46caffeine and alcohol are big ones for bad sleep, not just stress. Having a hot room or too many
00:49:54blankets is another mistake that a lot of people make. You can get those beds that cool you off.
00:49:59Eight sleep. Eight sleep. Anyone that's not using an eight sleep, it's medieval. I understand they're
00:50:03expensive, but there's no one that I've got to do. Yeah, they're a partner on the show or whatever,
00:50:08but this has got nothing to do with it. Every single person that I've got to try it
00:50:12can't believe what life was like before they had a cooled. And there's other cheaper versions out
00:50:18there, I'm sure. Eight sleep's the best, but there's other ones that you can get.
00:50:21Trying to cool your bed from outside of your bed when the job of your bed is to keep the temperature
00:50:27in the bed the same is kind of a little bit like fighting against the tide.
00:50:30Yeah. Oh, exactly. And you should wake up every morning feeling totally rested, excited about the day.
00:50:36If you're waking up and like, oh, I need a coffee. Oh, I need a shower. You're probably not getting the
00:50:42sleep that you need. You mentioned stress as well as kind of the fourth pillar when it comes to
00:50:47lifestyle. What does that look like? How do you come to think about stress as a longevity doctor?
00:50:52Yeah. Well, you can measure cortisol, for example, um, or DHEA cortisol levels. We're all stressed. You
00:51:00know, the, the old days of sitting around a campfire, not really there anymore. We're driving to work.
00:51:07We're worried about income. And so what we want to do is, uh, learn to, to deal with the daily stress.
00:51:15The world is changing faster than ever. So what, what I've learned personally is really not to let
00:51:22worries of life get me down. Um, I try not to focus on them. I have a happy place, which is an orchard
00:51:30uh, on Cape Cod and my mind when it's stressing out and I feel my body tense up, I take myself there.
00:51:38I breathe. I'm amongst the trees. Um, if it gets really bad, I go there physically and do some work,
00:51:44but yeah, it's, it's all about learning not to ruminate. Um, and a lot of us, A-types, I'm sure
00:51:52you in your success are like that. What did I do wrong? I could do that better. I'm worried about
00:51:57tomorrow. I'm worried about next week. I'm worried about 10 years. Um, don't do that. It took me 50
00:52:02years of my life to figure out don't do that and how not to do that. And the last. How do you stop worrying?
00:52:08You have to train yourself. It's like, don't be an idiot. Stop thinking about it. Um,
00:52:12it's not going to kill you if you distract yourself with something else. Overthinking something is,
00:52:18is a real, uh, uh, issue for modern life. And, uh, so I don't do that anymore. If I, uh, find myself
00:52:25overthinking, I'll just say, I'll think about it later, put it off to the side. And I used to be the
00:52:29kind of guy that I had to text back immediately and email back immediately, put it aside. I'll get to it.
00:52:36I think a lot of people are riven by
00:52:40the overthinking intrusions that they just can't get their brain to focus on what's in
00:52:46front of them. There's always this concern. There's always this situation that could be a
00:52:51little bit worse. This thing that could make life a little bit harder. That's coming down next.
00:52:55And yeah, you're, you're kind of being puppeted by these ghosts of the future that haven't yet come
00:53:00about. Yeah. That's the thing. What you realize when you get to my age, I'm now 57 is that it's never
00:53:08as bad as you think. And what I do now is I depend on myself. I know that these big problems in my life,
00:53:15and I've had big ones, deaths and issues. Um, you get through it, you trust yourself, you know,
00:53:23you know, maybe when you're a teenager and you're in your twenties, you don't know that you can get
00:53:27through these things. I'm at an age where I know I'm not going to die. I'm going to get through it.
00:53:31It's going to be okay. Um, if I have a problem, I'll solve it. Um, the sooner you can realize that,
00:53:38that you are capable of anything, if you put your mind to it, then you shouldn't stress about problems
00:53:43that come up. Tell me if this sounds familiar. You train regularly, you eat reasonably well,
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00:54:42Okay. Let's talk about your current drugs stack. What are you taking? How's your daily stack
00:54:47changed versus what you were doing when you wrote the book?
00:54:51It hasn't changed. That's the amazing thing. I thought I'd have to change things depending on
00:54:54the science, but the science has held up. So in the morning, and if you go to page 304 of Lifespan,
00:55:01it's still there. And I still do that. Risveratrol. It's been back and forth, controversial. It's not
00:55:09controversial in scientific circles. There's a few naysayers, but they make a living out of it.
00:55:14Resveratrol is from plants that are stressed and they activate SIRT1, this resetter and slower of the
00:55:20epigenome noise. So I've been taking about a teaspoon, call it a gram of resveratrol every morning,
00:55:28almost every morning for the last, gee, probably 20 years. Doing all right. It seems to help in
00:55:34clinical trials. It's been tested in a number of clinical trials. I mix it with either a little bit of
00:55:39olive oil or Greek yogurt or vegan yogurt. And it's been good to me. I also take that with NMN,
00:55:53which is an NAD supplement. It's a precursor. We studied both in my lab and we just resubmitted a
00:55:59paper. This is something I can reveal. We just resubmitted a paper to be published that showed that
00:56:06NMN is very good for the health of old mice and can extend the lifespan of mice, particularly females.
00:56:13And so that'll come out probably resubmitted.
00:56:16Yeah. We had reviewers' comments, criticisms, spent another year working on it to please them
00:56:22and send it back. We'll see what they say. What was the controversy? Because I know
00:56:27since the last time we spoke, there's been some furor around resveratrol, some more furor around
00:56:34NAD, maybe NMN as well. Can you explain what happened?
00:56:37Yeah, sure. These are all typhoons in a teacup or whatever it is.
00:56:43I can't stop drinking your drink. It's very good.
00:56:45Good. That's all I needed.
00:56:48So let's start with resveratrol. I try not to bore everybody. SIRT1 is an enzyme. I'll use my hands.
00:56:54It's an enzyme that carries out reactions that stabilizes the epigenome so it doesn't decay. So
00:57:00think of it as stopping the corruption of the software. More SIRT1 is better. So there are two
00:57:05ways to activate SIRT1 with a pill rather than exercise and dieting. And if you do all of them,
00:57:12I think it's the best. So you can either take resveratrol and that we showed in 2003,
00:57:19a long time ago, I'm old, activates SIRT1 directly. So the enzyme is removing chemicals from the epigenome
00:57:28and making it stable. And it can do it slowly. You know what a Pac-Man is. You're old enough.
00:57:35So it's chewing away chemicals, stabilizing things. The faster the better. Resveratrol binds
00:57:42physically to the enzyme and now makes it chomp faster. Okay. The controversy that came up was
00:57:47that Pfizer, a team at Pfizer, not the whole company, just a group in the company, put out a paper in 2010
00:57:53that said resveratrol doesn't do this. It must be an artifact. It's doing something else that makes
00:57:59it look like this. So we then spent three years testing that and found exactly how it works to the
00:58:07atomic level. We could even block it by changing an amino acid in this protein. And we actually have
00:58:12a study now that we've made a mouse that has this block and resveratrol doesn't make the mouse
00:58:18healthier anymore. It doesn't live longer. So that's as good as evidence that you could get that we were
00:58:23right in the first place and Pfizer was wrong. And we've put out papers since and others have shown
00:58:29that we were right. So no controversy. Going head to head with Pfizer is no small task.
00:58:34It was brutal. That was one of the hardest things in my life because I remember trying to defend
00:58:40myself in public. It was on NBC. And I said, I'm not sure what Pfizer is doing, but our chemicals
00:58:47don't kill mice and they activate the enzyme. And the comments were brutal. Sinclair thinks he's better
00:58:53than Pfizer if Pfizer knows what they're doing. I will say that I don't have ill will towards those
00:59:02scientists because it's the job of scientists to challenge theories. What I do have a problem with
00:59:09is the people who still say it's wrong and are trying, you know, just to get at me.
00:59:14What's the remnant? If you've put something out which pushes back against Pfizer, what is the remnant
00:59:19argument? There isn't one. The problem is that what I've gotten to see in my career over 30 years
00:59:27is the media loves the negative story, but the redemption story isn't as popular. So it's never
00:59:34come out in these journals like nature. They put out the negative story, but they never did the, oh,
00:59:42that was wrong. So it's just a matter of reporting. But in scientific circles, everyone's read our
00:59:48science paper from 2013 and it's not debated. That the evidence is put to rest in your opinion.
00:59:55Yeah. Yeah. It's at the atomic level. Unless you want to complain about atomic theory, you know,
01:00:01we're done here. Okay. And what happened with NAD, NMN?
01:00:07So yeah, let's bring everyone up to speed on what NAD is. So SIRT1 also can be activated by giving it
01:00:13fuel, which is NAD. SIRT1 chomps with NAD. And in fact, this is not often known. The chemical that it
01:00:20takes off the epigenome structures is donated to NAD. So without NAD, you can't take the chemicals off.
01:00:27And more levels of NAD make it work faster and better. And if you give it to cells, you see more
01:00:33stable and healthier cells. There was dogma that NAD levels went down with aging and that boosting it
01:00:43back up was healthy. So the second part is true. We have shown in cells, in animals, and even in humans
01:00:51for the last and by we, I mean the field, not just my lab, that raising NAD levels above normal baseline
01:00:58is very good for humans. Okay. I can give you examples. Shelley Basin, you could look up in PubMed,
01:01:05he's got a couple of really good papers giving NMN, which is the precursor to NAD to people that are
01:01:11either obese or pre-diabetes or even super fit ones. Maybe the super fit isn't published yet,
01:01:18but he's done the work and reported about it. You see improvements from lipids, whole bunch of lipids,
01:01:26cholesterol, blood pressure, body weight. So raising NAD, I think most people would say that it's good
01:01:32for humans and animals. Okay. And again, we're going to publish that it's good for longevity too.
01:01:36Where the debate that came up, I think you're talking about the one that was maybe a few months ago.
01:01:44Somebody showed that human blood levels in white blood cells, the white blood cells don't have
01:01:50less NAD as you get older. So some people who love to make a living of being naysayers,
01:01:55especially towards my career, jumped on that and said the whole theory is wrong. If white blood cell
01:02:02NAD levels don't go down with aging, then the whole theory must be incorrect, which as you can tell is
01:02:07complete BS. In fact, we've known for probably a decade that that was true and it doesn't affect
01:02:13the theory. We know that raising NAD levels in humans either by exercise or by supplementation
01:02:20is good for you. So it was crazy to say the whole theory fell apart. It was just a way to get clicks,
01:02:25I think. What's the status? I'd looked at something to do with it was a pharmaceutical,
01:02:32then it was a supplement, and now I don't know what the level of access is with NAD and stuff
01:02:36at the moment. How's that classified? Yeah. Just a final thought, there is a really good study that
01:02:42showed that people who have lower levels of NAD in their muscle, I think it was not as metabolically
01:02:50active as those that have higher levels or they had metabolic syndrome. Anyway, we could check it out,
01:02:56but there is some good correlations between NAD levels and age-related conditions. I want to be
01:03:03accurate. All right, so the FDA thing. Basically, it was that there's a rule in the US that if any
01:03:13molecule, whether it's natural or synthetic, goes into a human clinical trial, before it's on the market,
01:03:20people can't put it on the market, because then it negates the reason to do a clinical trial.
01:03:24And we need clinical trials to know if things work. Makes sense. The law makes sense. Where things
01:03:30got crazy was a company that I started called Metro Biotech started a clinical trial with NMN,
01:03:37and a little later, people started putting NMN on the market. And I've always said publicly,
01:03:42you can read it, fine, let's do both. Let's do the clinical trials, make a drug, it's going to be pure,
01:03:48it's going to be tested, and there'll be supplements that are less rigorously produced for people that are
01:03:53not sick. But for the sick ones who have diabetes or need a drug, we'll have that. Happy world.
01:04:02The legal team at Metro Biotech made a decision without my approval, actually with my disapproval,
01:04:09to write a letter to the FDA pointing out that there was this law that they shouldn't have
01:04:16simultaneously sales and clinical trials. I objected. The FDA initially said you shouldn't be selling
01:04:26NMN on the market in the US according to that law, though they didn't enforce it. And then it was
01:04:34recently reversed.
01:04:35So now it is enforced?
01:04:37No, I mean the opposite. The FDA, I believe, says it's okay to have NMN on sale now.
01:04:44Oh, interesting. Okay.
01:04:45There was a court case that I think resolved that.
01:04:48Are you still taking the baby aspirin?
01:04:50Yeah, I am. That's controversial, too.
01:04:53One baby aspirin a day?
01:04:55Yeah, the 81 milligrams. Though 81 is only because a trial did 81. It's not magical.
01:05:01Brilliant.
01:05:02But yeah, you could take 100 probably. But talk to your doctor.
01:05:06Do you want to talk about aspirin in detail?
01:05:07Sure.
01:05:09The reason for the controversy is if you dig into it, and I do this because it's my living,
01:05:15most people don't have time. The American Medical Association weighed the risk of
01:05:22having stomach bleeding and other complications versus lowering the amount of risk of cardiovascular
01:05:29events and came to the conclusion that looking across everybody, it doesn't make sense.
01:05:37But I'm totally against the word everybody when it comes to health.
01:05:41Everybody's different. So I believe in precision medicine. And there's a group of people, for example,
01:05:47that where it does make sense to take baby aspirin. It's been shown that there can be benefits.
01:05:53And it's those people, just as an example, who have high levels
01:05:57of lipoprotein A or LP little a. I'm one of them. So I continue to take baby aspirin.
01:06:04But these are decisions to make with your physician.
01:06:07What else? Because I can't work out whether we call resveratrol a supplement or a drug
01:06:13or a pharmaceutical. I'm sure you can get it in pharma grade. But what else from the
01:06:19not foods consumption stack are you taking? Because aspirin would definitely be in the sort of meds
01:06:25category, I suppose. What have we missed off?
01:06:27Well, there's whole websites devoted to what people think I take every morning.
01:06:30Okay.
01:06:32Set the record straight. What is it you're taking?
01:06:35Well, that will, I'll have to come back for another show or people can listen to my podcast.
01:06:41Yes.
01:06:41Because it's a whole, it's a whole box of things and I'm not taking them all the same day.
01:06:45But I still like alpha lipoic acid for mitochondrial health. So I've been taking that for over a decade
01:06:54now. I did a PhD on it, so I know a little bit about its benefits. But that was a long time ago.
01:07:00Let's see. CoQ10, of course, because I'm actually on a statin. I might switch to a PCSK9 inhibitor
01:07:05because it's more effective, but my family is very high cholesterol.
01:07:08No, I'm on Repatha.
01:07:09Great.
01:07:09Yeah.
01:07:10You like it?
01:07:11I've actually stopped taking Repatha because I want to see if it's causing some brain fog.
01:07:17Oh.
01:07:18That is sometimes associated. It's anecdotal. But I noticed ApoB went through the floor,
01:07:26fucking brilliant, brought everything back in line. Isn't that lovely? Brain stopped working quite in
01:07:34the way that I wanted it to. Okay. Well, let's see what happens if I take a little bit of a break and
01:07:38let's see if brain comes back in line with where I want. But I found Repatha largely. I've got the
01:07:43every two weeks one rather than the monthly. And that's been good. But I've also been taking
01:07:47telemissartin as well because I didn't realize this until, I guess, I've done a lot of health
01:07:54discovery since the last time that we sat down. I have every polymorphism under the sun for somebody
01:08:00that's going to have high cholesterol and high blood pressure. Just a really perfect suite of
01:08:07hyperabsorber, hyperretainer, all of the dispositions that you want.
01:08:11Are you on Zedia?
01:08:12No. What's that?
01:08:15That's the common name. I thought I'd use it.
01:08:17It is the drug that blocks uptake of cholesterol. So the combination of a statin and
01:08:27the Zedia has been shown to be very effective at low and cholesterol.
01:08:30The supplement industry is full of products making claims that they can't back, which is why I'm such
01:08:34a massive fan of Momentus. Their co-founder Jeff Byers played in the NFL and saw firsthand just how
01:08:39wildly the quality of supplements can vary, so he built Momentus around a higher standard.
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01:08:55what's in the tub. It's why Momentus is trusted inside all 32 NFL locker rooms. It's why I've trusted
01:09:01them with my own supplements for years. Best of all, Momentus offers a 30-day money-back guarantee,
01:09:06so you can buy it and try it for 29 days. If you don't love it, they will give you your money back,
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01:09:16money-back guarantee by going to the link in the description below or heading to livemomentus.com/modernwisdom
01:09:20and using the code MODERNWISDOM at checkout. That's L-I-V-E-M-O-M-E-N-T-O-U-S.com/MODERNWISDOM
01:09:26and MODERNWISDOM at checkout. I did carnivore toward the back end of 2024, meat and fruit, technically,
01:09:34for six, nine months or so when I was recovering from living in a house with toxic mold. It was really
01:09:39brutal, but I actually felt phenomenal. It looked great, shredded, jacked in the gym, energy was good,
01:09:46a little on edge, like a little adrenaline-y all the time, but that's maybe to be expected,
01:09:51right, without any starch or carbs to sort of really bring you into land. And I managed to get
01:09:57my cholesterol up into the 400s, which- 400s? Yep. Yeah, it was really impressive. It was kind
01:10:02of like a personal- only briefly. You had creamy blood. And then brought it back down. But
01:10:09it's kind of what I've come to- you're right to say that
01:10:14everybody is different. Everybody has a different system. And the fascinating thing when you do these
01:10:20sorts of playing around with self-experimentation and intervention is you find out there's something
01:10:25that can make you feel amazing, make you look amazing. It's like in all of the subjective metrics
01:10:31that I care about. Right.
01:10:32Shit's going great. Except for the one that might kill me pretty quick. And then I went and did a
01:10:38clearly scan, which is fucking unbelievable technology, by the way. Basically, this special type of
01:10:46contrast scan is able to look inside of the arteries of your heart and look at plaque buildup without
01:10:53having to do anything invasive. It's magic. And I had a small, very small, but mild amount of plaque
01:10:59progression. Okay, I need to put the kibosh on this. Regardless of how jacked and alert I feel, I need
01:11:06to eat a much more sort of Mediterranean, low-fat, low-protein diet. Please. Yeah.
01:11:12Yeah. And I know it's not proven, but I do like the idea of plaque reversal. So there's two ways that
01:11:20we know of that might do it. One is reducing your LDL so low that it reverses. So Repatha,
01:11:26that kind of drug. There's an oral PCSK9 inhibitor just has come on the market, which I've
01:11:34got a prescription for. I'll try it out. That's one way. And then the second one was based on a study
01:11:40that had 1000 people in China. I know it's not the perfect study, but to me, it looks like it might
01:11:47be true. And given that this substance is so safe, the downside is cost me a few bucks. Natto kinase.
01:11:55Do you know about natto kinase? No, what's that?
01:11:58So do you know what natto is? It's natural?
01:12:01No, you're lucky. Anyone who's been to Japan probably has seen at breakfast in the hotels,
01:12:09they serve this goopy, bean, sticky substance that if you lift it up, it looks like cobwebs and it smells
01:12:16like vomit. So Serena eats this stuff. I don't know how she does it. I have to hold my nose.
01:12:22That stuff, it's bacillus subtilis and smother bacteria eating soybeans. They found that there's
01:12:28an enzyme in that stuff that if you swallow it, it can remove, well, at least it looks like it can
01:12:34remove plaque, hence natto kinase. Kinase is the enzyme, natto is the food. And so I swallow,
01:12:45depending on the day, about 10,000 units of this stuff every morning.
01:12:49And some sort of capsule?
01:12:51Yes, just a capsule. You swallow it in the morning and I'm going to measure it. I typically do an
01:12:57ultrasound on my carotid every year. It's like the clearly, it's just on your neck and
01:13:04you can actually do your intermediate thickness, which is important. Tell your doctor if they do that,
01:13:10tell me my IMT. And that is a number that will tell you very similarly how you're doing
01:13:15cardiovascularly for your whole body. And I'm going to see if natto kinase makes a difference.
01:13:20Fascinating. What's all this hype around erectile dysfunction medication?
01:13:26That's a lead in question. Well, yes, it's recently come into social media because it was found that
01:13:35these ED drugs are also good for some types of cancer and can change the immune system so that
01:13:42it goes from protecting the cancer to killing it. And I tweeted out what's not to love and millions of
01:13:48people saw that. Um, but I'm serious. I take, uh, uh, what is it? Um, Cialis is the common name. Um,
01:13:58to doubt Phil, um, every morning, that's a low dose. It's just, uh, a little bit. And I do that because
01:14:07in 2012, we published a paper that showed that one of the most pernicious causes of aging
01:14:15is low blood flow. And then we could reverse that with NMN through cert one, more blood flow.
01:14:22And it's really underappreciated how much a lack of blood flow leads to diseases, your,
01:14:28especially your, your muscles and your brain. And so I take this low dose in the hopes and expectation
01:14:34that I will, if I get dementia, it will be a decade later. And now add on that cancer killing, it's an
01:14:42amazing drug. And it was actually not even developed initially for these.
01:14:46It was an angina medication. Exactly. Do you know the story of why they realized it had that side
01:14:52effect? Um, was it, was it pulmonary? They, when, when they were doing the trial,
01:14:58typically you do a meds trial and patients come back into the lab and you ask them to give the drugs
01:15:04back and nobody has an issue, but none of the guys wanted to give the drugs back anymore. And the nurses
01:15:10noticed that the, uh, patients, when they were doing their interviews were sitting cross-legged
01:15:16and they had this strange contorting of the posture to try and hide the fact that they all had hard-ons
01:15:23and, uh, it, they said, Hey, we, we need the angina thing. We're not so sure about, but we've done
01:15:28some wonderful stuff to the penis. Uh, well, I can say taking a low dose, the good news is it doesn't
01:15:34make your, your penis get erect without warning. Okay. That isn't a problem. Yep. But the low dose
01:15:39really, um, I've let's put it this way. I haven't had any downsides yet. Fantastic. Uh, there's,
01:15:45there's one other thing, Chris, I want to say, which before I forget in my old age and my lack of
01:15:49blood flow is, um, so there's a, there's a study in mice at least that hints that lack of blood flow to
01:15:55hair follicles is a reason that you lose hair. And so my hope scientifically is that, uh, continuing
01:16:02to get blood flow in my hair follicles will keep my hair more hard-ons, less balding. That's the
01:16:08equation. Yeah. I don't, I don't know which one I'd choose if I had one, but that's true. I guess a lot
01:16:14of guys don't have that choice. Uh, human had said something to do with the, uh, perfusion of the
01:16:19prostate as well. Uh, that opening up blood flow is especially given how close you are to ground zero
01:16:27might be a, like a useful side of it. I don't know, man. I, I said my favorite conspiracy theory about
01:16:33this. I hope that it's working. I hope that it's a, uh, like pretty much all gains intervention that
01:16:40everybody can use. But my favorite conspiracy theory about why erectile dysfunction medication is being
01:16:45pushed so hard is that it reduces any of the stigma of any one guy having to take it. So darling,
01:16:50I've got to take it. It's important for my hair. Dr. David Sinclair told me that it would stop me
01:16:54from going bald. And also, you know, a great grandma, she had, she had Alzheimer's is very
01:16:59important for my neurodegeneration. And my, you don't want the prostate, you know, granddad,
01:17:02he had the prostate thing. So it's the, the ED. You don't need to worry about that. It's normalizing.
01:17:06There's a lot. I think you're a hundred percent right. And, uh, I'm sure there have been some
01:17:11wives like, honey, why are you eating 10 of them? Yeah. Yeah. Um, what about omega-3s? You know,
01:17:18omega-3s commonly touted as something that's very important for people's longevity. Why do you come
01:17:24in to land on omega-3 levels and supplementation? Uh, I take an omega-3, um, that the data looks really
01:17:32pretty good that, uh, if you have some of that, it's anti-inflammatory, whether or not it totally
01:17:36prevents heart disease. It's controversial now, but. Have you got a brand that you prefer?
01:17:45Yeah, but I won't say it. Okay. I'll tell you what I use. Nordic Naturals 2X are the best.
01:17:50Um, I do like, I do like them. Yep. Um, their products are really pure and distilled. So you
01:17:56want to avoid the cadmium and lead products. The what, what? The ones that have heavy metals. Okay.
01:18:01So I, I mean, I remember this, my mom would tell me this 25 years ago when I was a kid and she would
01:18:08be taking, and there would always be this line of low quality cod liver oil back in the day,
01:18:15low quality omega-3 supplements aren't really that good for you. So this is like, you know, mythological
01:18:22fucking ancient wisdom. It, it really is. And actually while we're on the topic of, um, contamination,
01:18:28I, uh, and other labs have measured, uh, supplements and they're often contaminated
01:18:33with things. And I even got sucked into a lawsuit because I said, I tested this product on it or this
01:18:40type of product and it had contamination. But I do want to say at the risk of some litigious activity
01:18:47against me that NMN and these NAD precursors can have contaminants in them. Now I don't sell,
01:18:56I don't market anything. I don't get any money despite people using my name and even video across
01:19:02the internet. So I have nothing to gain or really lose by this. Well, I've got a lot to lose, but
01:19:07nothing to gain. NMN can have things like, well, first of all, I think the study that was published,
01:19:14it's worth looking at by Andrea Meyer. Um, she's out of Singapore. She found that a lot of the NMN
01:19:20supplements didn't have NMN in it. And if they did, it was a low amount. And we found in my lab,
01:19:25which I don't think is in Andrea's paper is that there is endotoxin in NMN bulk and supplements.
01:19:33Endotoxin comes from bacteria, causes inflammation. It's part of the purification process, but they don't
01:19:38get rid of it. And we found out the hard way we were feeding it to mice to make them live longer,
01:19:42which is not going to work if it's contaminated. Hang on. So even the NMN that you were using in
01:19:47your lab that you thought was pure was so contaminated that it was infecting the study
01:19:52participants? 100%. Wow. So we've had to really work hard with manufacturers to get it really pure.
01:20:00How hard do people need to work? If somebody is taking an NMN supplement now,
01:20:04is there anywhere that a normal person can go that's not going to risk being contaminated?
01:20:09Hmm. Well, if I ever mentioned a brand, it's going to be, it'll blow up the internet,
01:20:15might not bring it down, but, um, I will say that to help the viewers, um,
01:20:22the, and the listeners of this show, I would go for a company that has a strong reputation
01:20:29that provides the analytics. So sometimes they give the spec sheet and you can see the purity.
01:20:36And, um, you know, some companies, they've got such a big reputation. They're not going to risk
01:20:40adulterating it or putting something else in it or giving you less.
01:20:44Um, GMP is important always. Any supplements should be, uh, good manufacturing practices. Um, USB label,
01:20:51look for those badges of purity. Um, and if your company that you like doesn't share the analytics
01:20:57online, you can write to them and say, can you please share that batch? And they often do that.
01:21:02Right. They're not cheap interventions for people. And if you're spending a lot of money on something,
01:21:06you want to make sure that it's actually, the worst thing is I'm taking this thing that I think
01:21:09is going to make me more healthy and it's actually making me sick.
01:21:12That's the real problem. Um, and so what, um, and I'm going to do a shameless plug,
01:21:17if that's okay. Um, I'm launching a community,
01:21:21a website community for us to figure this stuff out together. I'll be testing products. We'll learn
01:21:27what works together. Um, and I hope that it becomes the world's largest longevity community.
01:21:33What does the, what, what's the community built around? What is it?
01:21:36Yeah. It's called lifespan.com. So my show is lifespan. This is the website version. Um,
01:21:42my goal ultimately is to fix healthcare across the planet. We've done a top down government, big
01:21:50industry HMO. Um, we know that doesn't work. The U S especially is spending close to 20% of GDP on the
01:21:56healthcare and got some of the worst healthcare. So you've got to do something. So grassroots movement,
01:22:01lifespan.com will be a community that comes together to learn what works, what doesn't.
01:22:06Um, and eventually where I want to take this is that we, we change how healthcare is done
01:22:12and with AI, with knowledge, with, you know, we're also funding medical research and testing a brand.
01:22:19So we know what's pure and we'll find new medicines together. I want to share in the profits of that
01:22:26with all of the members. So that's being launched soon. Um, that's cool. It's probably launched by now.
01:22:32Um, there's for members so that there's an unpaid versions. You can do show notes and you can see
01:22:38some, uh, some stuff, but if you, um, pay the $8 a month, um, we've pulled together something really
01:22:46interesting. We've got this community that we built, but also there's information that will basically
01:22:52compliment what we've been talking about today. There's a magazine world's first magazine written
01:22:58well-written by people who are doing the research. So you don't have to rely on some, uh, newspaper or
01:23:03a reporter who doesn't know anything who also wants clickbait. Um, I actually brought a copy of this
01:23:08magazine. I had it printed in hard copy just for you. Oh, let's get it. I want to see. You haven't
01:23:14seen it. This is, this has been hidden here. This is lifespan magazine. First one I've given out to anyone.
01:23:22And this is a gorgeous magazine that every member gets online. What if aging isn't damage, but lost
01:23:29information, a radical idea now entering human trials. Oh, that's, that's the paper from nature
01:23:35that I thought I'd give you as well in 2020 that changed everything. This is so cool. Thank you.
01:23:40You have a look inside. I'm so proud of how it looks now. Um, this is going to be coming out every
01:23:46month and it's got about a hundred pages of the real science, the real stories of what it's like
01:23:53and what we're learning before it even comes out in journals and in the media.
01:23:57Oh, this is cool. It's very beautifully put together. Beyond your birthday, Steve Horvath
01:24:03on the science of epigenetic aging. I know Steve Horvath. Yeah. Yeah. Steve discovered the
01:24:07epigenetic clock. Can a simple, simple multivitamin mineral supplement slow down aging?
01:24:12This is awesome. Congratulations. Thank you. Congratulations. I'm very proud of the team. It's a,
01:24:17it's a small but mighty team that we really, we're really driven by mission. We want to change the
01:24:22world and we want everyone to join us in it. Unreal. Uh, okay. Other interventions,
01:24:26other stuff that's happened. Cause since we, since we first sat down the world of longevity,
01:24:34biohacking has really sort of, it's not exploded. I think it's, I think it's become more sophisticated.
01:24:39You may say otherwise, the evidence may say otherwise, but at least from the like self-experimentation,
01:24:45uh, you know, 2017, 18, 19, it was a lot of the biohacker's handbook. It was, you know,
01:24:54Ben Greenfield's friend of the show sticking ultrasound things on his penis to see if he can
01:25:00improve his, his erection quality and his orgasm length and stuff. And then it seems like it's really
01:25:05come on data backed a lot more, um, evidence-based crowd stepping into this.
01:25:13Well, thank you to you, for example, uh, guys like you are bringing scientists like me and people who
01:25:19know what they're talking about so that people can hear it from the horse's mouth. Whereas before it
01:25:24was just somebody hyping and selling stuff which you couldn't trust. It's true. I mean, what's been
01:25:29interesting has been to see, at least in, in Greenfield's case, like how right he was about
01:25:34tons of stuff super early on. Yeah. Though I didn't mean to imply Ben was one of those people.
01:25:38But there's so many people, even, uh, uh, uh, Timo, Timo Arena, was it that wrote the biohacker's
01:25:43handbook? It's his coffee table book. I've still got my house in Newcastle. And I look at some of that
01:25:48and it's the same as the bodybuilder thing. So many bodybuilders stumbled onto a particular
01:25:55way to look at health or dieting or whatever that a decade later, science then comes back around and
01:26:01says, Hey, that's the way. But then also there are a lot of people that throw shit at the wall and much
01:26:06of it doesn't stick. Yeah. One of the most, uh, popular interventions that people are talking about
01:26:11contrast therapy, sauna and ice baths. What does the evidence say around cold and heat exposure for
01:26:18longevity? Um, increasingly we're learning, um, in 2019, when you and I first met,
01:26:25there was very little evidence actually. Um, and you're right by hacking was something that was
01:26:29looked down upon, especially by doctors. Um, and the public didn't know what was going on.
01:26:34Uh, then came the pandemic and most people saw their mortality and it's like, what are we going to do?
01:26:40And it's amazing to see what's happened since that it's become mainstream. And even doctors have had to
01:26:46learn about this because their patients are coming to them with more knowledge than they have,
01:26:51especially with AI now. Um, but we are, we are in a world now where the individual can know more about
01:26:58a certain topic than their own physician, which is incredible. Um, that does include sauna and cold
01:27:03bouts. When we met 2019, there was a little bit of data and saunas and nothing on cold bouts,
01:27:09except a mouse dunked in the cold. Um, now there's much better evidence. Um, I put it in my book,
01:27:14lifespan because, uh, I was told by the editor that that would be interesting, but I was hesitant
01:27:22because there was such little data on saunas and nothing on ice baths really. That's different now.
01:27:27I can now say as a scientist scouts honor. I was a scout. I forget how we do it. Um, that
01:27:35definitely sauna. There's a lot of evidence, mostly, uh, Nordic men have been studied, uh, less women,
01:27:41but if you do regular, what they call sauna bathing in Finland, a few times a week, your rate of heart
01:27:48disease can be much less than, and that is reproducible. So that I think saunas are great.
01:27:54Um, I try to do some of that myself, um, as hot as I can bear. Ice baths contrast. It makes sense
01:28:02scientifically, hasn't really been studied, but, uh, cold therapy, we do know it can activate brown
01:28:09fat, which is very good. What does that mean? Well, so we, we actually going back in history,
01:28:1530 years ago, we didn't know that we adults, humans had, uh, brown fat. Babies have brown fat.
01:28:22It's a highly metabolically active type of fat in babies that keeps them warm because they can't
01:28:28shiver initially. Um, and then using pet scanning, people at Harvard, some friends of mine discovered
01:28:34that adults can have brown fat on their own bodies as adults. Um, often they're in the back.
01:28:42You can get it more brown fat by, by doing cold belt, cold plunges and being cold. Um,
01:28:48do you want more brown fat? Yes. So I was going to say the, the brown fat's full of mitochondria,
01:28:55which are healthy. They, brown fat seems to secrete factors that are good for health. Um,
01:29:01but yes, people that have more brown fat tend to have better metabolism in general. And they also
01:29:07burn more energy, which is good in today's world where there's too much food around. So yeah, in general,
01:29:13yes, brown fat is considered very healthy. Um, but the older you get, the harder it is to,
01:29:17to make and convert from white to brown or beige. And, uh, so my view on that is, and that's true
01:29:25for mice. I'm not sure it's true for people, but let's say it is. I still believe that the earlier
01:29:30you start to build up your brown fat reserves, the better because by the time you're in your eighties,
01:29:35it's hard. Cold exposure is a good way to do that. Exactly. Right. Um, I don't know if it's true,
01:29:41but I like to experiment with sleeping a little cooler. And as I wrote and have said a few times,
01:29:48turn down the temperature, don't sleep with a lot of blankets. We've already talked about eight sleep
01:29:53beds. That is a way probably to burn more heat, more energy, but it might help if you're feeling
01:30:00cold during the night, uh, build up brown fat. That is a might, you will get more brown fat if you
01:30:07cold plunge, um, and do those kinds of things roll around in the snow. It is controversial though. I did
01:30:13see a little bit of pushback against Wim Hof and what he was saying. It may not be as spectacular
01:30:20as what he's claiming. The evidence for heat seems to definitely be stronger than the evidence for cold,
01:30:24like 10 to one, 20 to one. That's what I'm saying. Yeah. And I, it's strange because the
01:30:30immediacy of the reward, if anyone's had a cold shower or used a cold plunge, you feel really good.
01:30:35As long as you stay in for a little bit, you feel so good afterward, but I'm, I like to do it. It's
01:30:44fun or whatever, but I would probably take a sauna 20 times over taking a cold plunge. If I'm going
01:30:51to try and do something for my health. I'm the same. I do a hot every, every day, including a steam
01:30:56shower, but, uh, I cold plunge probably once every two weeks at best by, by turning on the cold tap.
01:31:03What do you make of Brian Johnson's approach to longevity?
01:31:07Well, it's totally different. Um, putting the two of us side by sides. Some people do it's,
01:31:12it's not the same animal. Uh, I'm doing science. I'm doing the research and figuring out the molecular
01:31:17mechanisms. Um, he's a compliment to that. He is self-experimenting. It's not a clinical trial.
01:31:23Obviously he will admit that, but where I think Brian shines, um, is in a couple of areas. He's very
01:31:30courageous. I like that he stuck his neck out. I have a lot of, uh, admiration for those people who
01:31:37are brave that way. Um, he's also been, um, helpful bringing a spotlight to the field of longevity.
01:31:45And I remember a lot of my colleagues, uh, my highbrow colleagues in longevity
01:31:50really said, he's the worst thing that's, that's happened to us to this field. He brings a bad name
01:31:55to longevity, but I, I disagree. I think that he, that we as a field of scientists had a marketing
01:32:04problem. As much as we talked about longevity, it wasn't getting through up until 2020, almost
01:32:10nobody had used this word. Even Brian came along. Um, I came along, but definitely Brian got a lot of
01:32:16attention and I think it's been helpful to wake people up from their stupor. Uh, not everybody,
01:32:24but a lot of people just live their lives and eat whatever they want. Um, do a little bit of exercise.
01:32:29Brian said, we can be much better about this. We can science the heck out of this. And I love that
01:32:36approach. And so I think it's complimentary. I'm saying let's do real science, clinical trials,
01:32:43molecular, uh, but also with an N of one doing pre-treatment, post-treatment, see what happens
01:32:50under doctor supervision. We can learn some things too. Um, yeah, I, I think Brian deserves a lot of
01:32:58credit for, for that, for bringing attention to what you've got, you've got a highly unsexy field.
01:33:04I'm not saying Brian Johnson's sexiest guy on the planet, but he's definitely made an existingly
01:33:08unsexy field, at least a little bit more sexy. What knowing what you know about his approach to,
01:33:14um, the fundamentals for longevity? Have you got any smell test or sort of lick your finger to work out
01:33:23where the wind is coming from or you think, oh, he might really be onto something there. Is there
01:33:27something that he might be out ahead of where the, the data or the research or the science is at the
01:33:31moment? Um, not really. I, I, I don't pay as much attention to him as I probably, uh, should or could.
01:33:46Um, I do look at some of the, the blood work that he posts and, uh, there's a particular test,
01:33:54um, that's called the Dunedin pace of aging, which is a measurement of your epigenome changing.
01:33:59So we, Steve in the magazine, Steve Horvath discovered the epigenetic clock.
01:34:03For those of you who don't know what that is, it's chemicals on the DNA
01:34:07that change with time. These are like the scratches on the CD or the software corruption. You can measure
01:34:12that. You can do it before and after, or you take it every, you know, three months or every year.
01:34:19And Brian has published publicly his results and you can determine what is representative
01:34:27of your pace of aging. And his was, I recall something like 0.4 something. And one would be
01:34:34you're aging one year for every year. And you know, if you're two, you're doubling your rate of aging.
01:34:40So you're going to die early. According to that, that's one of the lowest paces of aging I've ever
01:34:44seen for a human. So that's pretty impressive. If that's maintained, he could live decades longer
01:34:51than the average. He's supposed to. Then he would, if he didn't take care of himself.
01:34:56Is that taking into account telomeres or no, with that Dunedin pace of aging?
01:35:00No, it's not. I don't believe so. It's just, uh, looking at the, what's called DNA methylation
01:35:07pattern on the DNA. What do you think are the biggest wastes of money that people spend on longevity?
01:35:12Oh, well, the overdosing of vitamins, particularly B vitamins. Um, I think that if you're on a vegan
01:35:22diet, yeah, you should make sure you're not deficient in any B vitamins. Um, generally,
01:35:28if you're taking a lot of multi, uh, what do you call it? Multivitamins, uh, it's excessive
01:35:36and it can actually be toxic if you have too much. So vitamin C, uh, can be pro oxidation,
01:35:42not antioxidant if you take a lot continuously. So overall, I'm not, I'm not for multivitamins.
01:35:50Um, I do believe you should measure your vitamin, uh, in your blood. And if you're deficient,
01:35:56you should make sure you're not deficient, but overdosing on vitamins, especially B, you know,
01:36:01you could do IV. Some people do that. I think, yeah, you'll get a short term hit, but I, I nibble
01:36:07on my B vitamins. I don't take the whole thing. I tried again, the self-experimentation over the
01:36:13last couple of years, recovering from this, this mold complex illness stuff has been interesting to say
01:36:18the least. And the start of last year, one of the potential culprits for why I was feeling so shitty
01:36:25was methylation. So did a bunch of genetic testing came back. I've got four different polymorphisms
01:36:30that make me suck at B vitamins, like one in the blood, one in the brain, one in the methylation,
01:36:34and one in the something else. One of the potential put forward, uh, explanations was,
01:36:40well, your mean collicular volume, your MCV is high. It's like just like 101 or whatever,
01:36:45which is just above the upper range. Oh, well, maybe this is something to do with Bs.
01:36:48I was like, okay, well, I'll try some, uh, intramuscular methylated B12, like 500
01:36:56micrograms. So you tiny, tiny, tiny, tiny little, it's almost like got to put a huge needle in your
01:37:00leg to put this teeny, tiny amount of B vitamins in. I didn't realize that you can get something if you
01:37:05push it too far called B12 induced confusion. So you can actually just make yourself confused and your
01:37:13brain gets very slippery, given that this was the thing that I was trying to push back against.
01:37:16What I'm saying is I know what happens when you push B vitamins too far. Um, and I actually did
01:37:20that the week. It was the biggest week of the show last year where I had Rogan. I was on Rogan
01:37:25on the Thursday and then recorded with Naval Ravikant on the Saturday. And I went into it going,
01:37:29I've like poisoned myself with fucking B vitamins. And now I can't think straight. It was fine. It was,
01:37:34it all ended up being great in any case, but, uh, yeah. Okay. So, um, spending too much money on,
01:37:39uh, vitamins, multivitamins is one of the biggest wastes. What else?
01:37:43Well, at the risk of being sued, um, I would say-
01:37:47That's a big cue.
01:37:48I'm not sure about, again, I'm not saying it's wrong. I'm just not sure about
01:37:55a certain laser therapy. Um, Serena, my partner loves shooting lasers at her body, but I-
01:38:03For skincare? Uh, internal as well.
01:38:06How do you shoot a laser internally?
01:38:10Well- Which, which hole does it go in?
01:38:12Yeah. Well, it, it shines on your skin back and forth. So I don't know if that
01:38:16is doing anything. I'd like to see some data on that.
01:38:18Is that like red light stuff?
01:38:20It's red light, but it's different colors and wavelengths.
01:38:22Oh yes. Yeah. I've seen those things. There's huge, big panels that people can stand in front of.
01:38:27Well, the red light is not crazy. So certain infrared, I've got near infrared panels. I'd have
01:38:33that actually, I'd shine that in the shower sometimes.
01:38:35Okay.
01:38:36And that, that science is coming around to confirming some benefits there. So I think
01:38:42that's fine. And the red light saunas, um, I'm going to get one and see how that goes.
01:38:45But the yellow lights and the others-
01:38:47Yeah. These other things, it looks like it's, uh, 4th of July, uh, in, in the house,
01:38:52but I'm not sure about that one. Um, but you know, you have got to be careful. What
01:39:00you say is BS now turns out to be true.
01:39:03This is where the biohackers get it right, dude. This is where the biohackers get it right.
01:39:06Yeah. Even peptides, you know, now we're seeing a lot of them are actually really helpful.
01:39:11Talk to me about GLPs. Cause you know, this has been, this wouldn't have even been a discussion,
01:39:17right? Three letters that I'd never have even heard put together the last time that we
01:39:21sat down in 2021 and certainly not in 2019. Yeah. What's your opinion on GLPs?
01:39:28Uh, in general, I'm very favorable. The, the number of studies that come out are showing
01:39:34that they're actually quite useful, especially micro dosing for healthy people.
01:39:39If you're obese, it it's, it's almost a must go talk to your doctor. I think if you can't lose weight
01:39:44alone, please consider using these. I think obesity is the fastest way to, to an early grave,
01:39:50it certainly ages you faster, but if you're, if you're like you and you're already, already close
01:39:55to optimal, are they useful? I think so that there are off target things besides obesity and metabolism.
01:40:05That seems to be important brain health, um, immune system, new things are cropping up all the time.
01:40:11It's as close to a longevity drug as we probably have right now, given really what we're seeing.
01:40:17Yeah. It's still early days cause we, we need to do longterm and there are some downsides. There is
01:40:23increased risk of, but low risk of kidney issues and even blindness. Um, don't panic. It's, it doesn't
01:40:30happen very often. So it's still really rare, but there it's not perfectly safe. So I just want to make
01:40:35sure people know that it's not like going out injecting, uh, candy into you or anything. Um,
01:40:41but I do think that, uh, and I have taken chill P1s, um, small doses to see how I would feel, what
01:40:48would happen. I definitely didn't have hunger. That was obviously what would happen. And I lost weight
01:40:53more easily. Um, I didn't take it long enough to be able to tell if other things were benefited. It looks
01:41:00like, uh, there's protection against, uh, dementia from those who are on the weight loss drugs.
01:41:08And this is from a mechanism other than just calorie restriction. There's something else.
01:41:12It's hard to tell, right? Cause most of the people on them are already overweight, but yeah,
01:41:18I saw a study recently. Um, I don't remember the journal, um, but I'll look it up and, and post it
01:41:24online on my social, uh, but I did see one that had really good evidence that it was not due to weight
01:41:31loss. It's just, uh, I would say in general, whenever I go to a longevity conference and there's a company,
01:41:37uh, like Novo Nordisk or Lilly, like you should see this latest study. We've shown that it does this
01:41:43thing that we didn't expect at all as a side effect. Um, and it's funny, these companies are now calling
01:41:49themselves also longevity companies. It's become that fashionable as well.
01:41:55Well, I suppose anything that, anything that reduces morbidity technically in one form, I mean,
01:42:03people that make helmet, bike helmets are longevity companies, you know?
01:42:06Well, you're right. And it's, it's a word that's unfortunately getting overused like anti-aging was
01:42:1230 years ago. And we'll have to come up with something else to do.
01:42:15I'm sure he'll come up with something sexy. Huberman says he thinks retitrutide will be
01:42:19a trillion dollar drug. Do you reckon about that?
01:42:22Um, I think it's possible. Uh, if the oral ones really look good, they may actually be, uh,
01:42:31even more interesting, but yeah. What is it? Something like 10% of Americans have either tried it or been
01:42:37on these drugs.
01:42:38I think 45% of Americans say that they would. Jerry, can you, uh, chat GPT, whatever the,
01:42:44the numbers are of GLP users and desired, uh, users in the USA to find that out. Uh, but yeah, I mean,
01:42:55what is it? Obesity is twice as big of an issue as malnutrition, as a, as starvation now globally.
01:43:01It's a billion people that are obese and half a billion people that are starving. It's like the number
01:43:05one leading cause of malnutrition globally is obesity currently around about 11% of us adults,
01:43:1129 million Americans ever used to GLP 15%. So that means that only what's that about
01:43:21two thirds of people who have used one are currently using one.
01:43:27And 91% of Americans are aware of them. Uh, 20% of us households, you say, uh, how many people
01:43:36want to, uh, I'm sure that this was from, uh, the most recent book that's Johan Hari brought out
01:43:44saying that it's a 45% of Americans would either have tried or want to try them.
01:43:56About 40% of us adults have obesity. Yeah. I will say that my number is correct. Yeah. That sounds
01:44:02great. Um, yeah, I, I mean the off target effects of this. Oh, it seems like people don't want to
01:44:11drink alcohol so much though. It seems their cravings for video games and porn get curtailed
01:44:17sometimes. I mean, I were getting into not just like neurobiology, but the framing of your own sense of
01:44:28self. What is your mission? I am the sort of person that is disciplined. I'm the sort of person that can
01:44:34do hard things. I don't need to eat that food. I'm not going to have that junk. What is the snowball
01:44:39effect that turns everyone into kind of a micro David Goggins, because they're working hard in one area of
01:44:45their life and diet is usually the first frontier that people get stuck into when it comes to discipline,
01:44:51right? I, on both sides of it, whether it's good or bad and okay, well maybe I'm going to get up on
01:44:55time. You know, I didn't eat the junk food last night. I'm on a bit of a roll. Yeah. Maybe it was
01:44:59pharmacopharmacologically, uh, assisted with what I did with my discipline around food,
01:45:05but I'm getting up on, or maybe there is some super magic wizardry that's going on inside of the brain.
01:45:10I don't know, but it's, it's definitely interesting and like it does feel the one,
01:45:16the one problem is it feels like an artificial solution to an artificial issue, which is we
01:45:21shouldn't have a food environment, which is so hyper palatable and calorie dense and attractive
01:45:25that we now need to medicate our way out of this.
01:45:28Yeah, it is dystopian for sure. Yeah. Um, but it's a blessing that, that obesity is declared
01:45:34a disease and then companies worked on it. And now we have these meds. I want aging to be the same.
01:45:40Aging should be declared a disease. We work on drugs and then we treat it. And in the same way that GLP
01:45:45ones now are saving the world, the same will be true. I believe 20, 30 years that people will say,
01:45:50why didn't we treat aging earlier? What common health advice today do you think people will laugh
01:45:56at in 50 years time? Uh, yeah, I think that, uh, eating three meals and snacking that this,
01:46:08you go to the, you go to the supermarket and there's health bars down the whole aisle,
01:46:12aisle that you're supposed to never be hungry. That's going to be seen as extremely toxic. You,
01:46:17you, your body needs to feel hungry sometimes, uh, have a break from food. So this,
01:46:23this trend of you're a bad parent. If your child feels hunger is going to be looked at like,
01:46:29Oh, what were you doing to our kids? Do you think AI is going to
01:46:35make bigger inroads into longevity research? I don't know what, I mean, again, you know,
01:46:41seven years ago when we sat down, AI, you, with your snail, you're drawing of a
01:46:44fucking snail on the whiteboard, there was no AI to be found. I don't remember what the snail was.
01:46:50I asked you about it at the time and it was something to do. It was explaining. It was
01:46:54some nerd stuff. This is how the molecular something, something. Oh, I remember we, we,
01:46:59we said, Chris is coming. Let's draw a snail. Throw a fucking snail. The idiot British guy will
01:47:03get him in and he'll be convinced that it's actually something really important. What's AI doing to
01:47:08longevity research? Yeah. Well, you asked me, do I think I know it's having a big impact already on
01:47:13research. My lab is thriving on it. It's going way faster. We just did something in a few months
01:47:20that would have taken us 160 years. And that was, that's using old technology that these days we can
01:47:27do. I'll tell you, tell you a story. That's funny. On Friday, I had a meeting with a student that just
01:47:33came to my lab over the summer and he's been here maybe three weeks and he's 19 years old.
01:47:40And I gave him a task. I said, according to the information theory of aging,
01:47:44if you look at all this data that's out there that nobody's looked at in a certain way,
01:47:49it should have this signature. And if it has that signature, we might be right. We might have found
01:47:55the backup copy to the software. And I said, okay, that that's your task. Go, go do that thinking,
01:48:01you know, help keep them busy for the next five years. Yeah, exactly. Because I've had about three
01:48:06people in my lab try to do that and they were not really successful. And he came in on Friday and
01:48:13he's with his team and his mentors. And we sat in my office and they've all got this big grin on their
01:48:17face and they threw up on the LCD screen in my office, the results. And this wasn't just the usual,
01:48:23I wrote some code in R and ran it. And we got some graphs. This was truly using AI. He was using one of
01:48:33the leading AI models. And he presented it like it was already published work with beautiful graphs and
01:48:41looking at terabytes of data that's out there in a new way. And he found something that professors and
01:48:48the experts in the field have missed for the last 10 years. And it's right there. There's this
01:48:53signature. He goes, I've given it a new name because I didn't know what to call it. This signature,
01:48:57I'm calling it the reverse tail. I said, what the heck is a reverse tail? And he said, well,
01:49:02I called it this because of that. And I said, dumb name. We'll think of a new name for it.
01:49:06But it's amazing. Love the idea of ship branding.
01:49:09Yeah. We'll work on branding later. But the fact that you found it is incredible. And that's a 19
01:49:14year old. I think he just finished high school and with AI, he's going to revolutionize biology,
01:49:20I believe. And that's just one kid. Imagine when whole teams are doing this.
01:49:24That's wild. That's wild. So have you, has there been anything as far as you're aware in the field
01:49:31of longevity that's been, uh, generated or inspired by AI that has gotten itself to
01:49:39trials testing and, and fully published as a world changer or is we still at the frontier of that?
01:49:46Not reading me meeting the real world yet.
01:49:48Oh, we we're, we're undergoing this revolution. So tomorrow's gonna be better than yesterday,
01:49:52but we're now at a point where almost somebody on their phone can discover a drug candidate.
01:50:02Whereas it would have taken a pharmaceutical company years, uh, and hundreds of millions of dollars.
01:50:08It's that world we can go from now that, um, uh, Demis has service has, and his team,
01:50:16not just him has cracked the code for protein folding.
01:50:19We now know all the chess pieces we were guessing, and it took years to find out what one chess piece
01:50:25looked like. And there's over 15,000 of these pieces now. These are all now modeled in 3D.
01:50:34Now we know not just how they look in 3D because they used to be one dimensional based on the DNA.
01:50:39Now we've got three dimensional amino acid structures. Now we're seeing how they fit together. Computer is
01:50:44actually smart enough to figure out which ones dock with each other. And eventually we'll figure out how
01:50:48they're all working together, uh, an artificial AI version of a cell. We can do in silico experiments
01:50:56at the molecular level now and dock trillions. Last year, it was billions. Now this year,
01:51:03it's trillions of chemicals, real drugs, and imaginary drugs.
01:51:08It's kind of like a virtual environment.
01:51:09Yeah.
01:51:09It's like a virtual lab.
01:51:10Yeah.
01:51:11Are these accurate? So if I run the synthetic lab, is it one-to-one with the real world?
01:51:18It's not one-to-one, but it increases your odds exponentially.
01:51:23Because you don't need to do test, test, test, okay, maybe this. You can discount a lot,
01:51:27and then the interesting ones get moved into the real world.
01:51:29Yeah. Yeah. And, and the old way of doing it, which felt really modern was you have libraries of little
01:51:36plates, hundreds of these little plates with 96 or sometimes 384 little wells, and each one has a
01:51:43different chemical that's physically in a freezer somewhere. You have to pull it out, give it to the
01:51:47robot. The robot then does its work overnight, tests it on cells, take a picture of the cells.
01:51:53You know, this kind of work is, is, is slow compared to today, which is we don't even need to have the
01:52:00fridge. We can make up trillions of potential drugs, test them, run it for a few weeks. It'll tell us,
01:52:07here's the top 200 and probably at least half of them are pretty good.
01:52:12It feels fucking primitive.
01:52:14And now we can do that experiment with hundreds instead of trillions. And trillions is impossible,
01:52:18by the way. Um, the most a pharmaceutical company would screen would be in the millions.
01:52:22Now we do trillions. Uh, and then you can even order them online. That's the thing that blows
01:52:27me away. We got a set of 200 that we think can reverse aging using AI. Um, and then I thought,
01:52:34oh, it's going to take us a long time to synthesize these 200. No, we just order them up. The company
01:52:39can make them for us in a matter of weeks. Now we've got them in the lab. We're testing them on human
01:52:44cells. We've developed an AI system that can tell us whether the 90 year old cells, skin cells from a
01:52:51human are going back to being 20 or anything in between just by looking at them. We paint them
01:52:56with dyes, different colors. And then where we're at is hopefully in the next month or so,
01:53:04give it two months, we will have a set of chemicals that can replace the current cocktail
01:53:11that reverses aging in the mouse that if you're paying attention earlier, not you, but listeners,
01:53:16if you've just joined us, I was talking about, we've got things that we can give a pill or a
01:53:21swallowing thing, a drink to a mouse swallowing thing, a drink, um, to a mouse and it reverses its
01:53:29age. We've got that, but it's a cocktail, a very secret cocktail, but it's got at least three things
01:53:35in it. We want to bring it down to one and turn it into either a supplement or drug or a patch or
01:53:42a thermal thing and some kind of cream or all of the above. But we're getting really close to being
01:53:49able to have the single molecule that can truly safely reverse aging in human cells. We'll test it
01:53:56on the mice and, uh, we'll run from there. How big of a role is expectation in how someone lives?
01:54:03If somebody thinks about aging as being associated with frailty and degeneration,
01:54:09can that actually make them live less long? Oh, you mean mentally if they're, yeah,
01:54:15that's well studied. If you're optimistic and you're enjoying life and you don't just get retired,
01:54:21just retire and be bored. Um, yeah, mental attitude is huge. Um, Robert Voldinger, a Harvard scientist,
01:54:27has found that the mental attitude and your social life is as important as your blood pressure and
01:54:33cholesterol, if not more important. And the one thing that was the best was have a reliable partner.
01:54:38I went through a divorce. It was horrific during COVID and I believe that it took years of my life. So
01:54:44it felt like it anyway, but, uh, it was, it was a shock. I didn't know it was coming,
01:54:49but, uh, it's brutal. Um, anyone that is young getting married, just beware. Um,
01:54:56we all change over decades. So that's, uh, something to keep in mind.
01:55:02But the point there is, uh, the amount of stress and cortisol that runs through your body when you have
01:55:07a really big life event, moving house, breakups, uh, death in the family, your own illness. These are
01:55:15age accelerators. And on the other hand, we've talked about today, the kind of things that
01:55:18keep you healthy. Um, the exercise, the diet, the social life, the sleep, the relaxation,
01:55:24these are all we know, um, are likely to not just slow aging, but eventually keep you disease free.
01:55:31And I do, I do want to mention that often people think, oh, I don't want to live longer because I
01:55:35don't want to be old for longer. That's not what we're talking about. We're talking about still being
01:55:39young and vigorous in your nineties. My father's almost nineties, 87. Now he'll be here on Friday
01:55:46from Australia. It'll be, I think second or third time he's come to the U S he was just in Japan.
01:55:51This is not a typical 87 year old. He is living life probably better than he did in his forties.
01:55:56He's out every night with different people, mostly, uh, uh, women that he's excited about. Um,
01:56:04nothing good friends. I won't, I don't want to disparage my father. He's not a dirty man, but,
01:56:11um, he, he is a very sociable guy. And in his forties, he was raising me and I wasn't easy to,
01:56:17to raise. I was a pain in the gut. He will, he will say he's never had a better time in his life than
01:56:22now at 87. If you were 35 or 40 again, and you could only do two or three things for longevity,
01:56:30what would they be? Um, definitely don't overeat, be lean, watch your weight, have a BMI of around,
01:56:39let's say 20 to 24. Make sure you, you don't get overweight. Um, obviously don't over drink and don't
01:56:47smoke. These are clearly really the worst things you can do having lost a mother to smoking. Um,
01:56:54so don't eat too much, right? Try to skip meals, uh, work out, maintain a very good body mass,
01:57:00um, and exercise. Those are the fundamentals. Everyone will tell you that. Um, what I didn't
01:57:05realize till I was in my fifties was how important food is. I thought vegetables were a garnish for meat.
01:57:11I love meat. Um, they taste, meat tastes great, but I've, I've switched over to being more plant
01:57:16focused and I've seen a great improvement in my overall health and biomarkers.
01:57:20So those are good. Learn not to stress. We've talked about, um, that took me a long time to,
01:57:24to learn that as well, but I've never been healthier because I've, it's been slow,
01:57:28but I've learned how to do all these things really well.
01:57:31I want to do a lightning round. So in a sentence or two, give me your review on these interventions
01:57:35for longevity. Okay. Okay.
01:57:37Okay. Creatine.
01:57:38We doing, how are we, how are we scoring?
01:57:40Just however you want. Give me a review. Yes, no, like it, don't like it, useless, buy it,
01:57:45do whatever you think, whatever you don't.
01:57:46All right. So creatine, um, in favor of it and take it.
01:57:52Stem cells.
01:57:53Interesting. And if you have a certain condition, like a, a joint that needs repair can be helpful,
01:58:03but it's not long-term solution.
01:58:05CPAP machine.
01:58:06Really important, um, for folks that have anoxia, lack oxygen at night for the brain.
01:58:15Um, though you could try other methods, which is lose weight, um, don't drink,
01:58:20uh, get a thin pillow, try to sleep on your stomach.
01:58:23CPAP hyperbaric oxygen therapy.
01:58:24Uh, in favor. There's good evidence that certainly cycling, uh, up and down in pressure is good for the
01:58:31brain and blood flow and, uh, have done it myself and, uh, have seen improvements in wound healing in others.
01:58:38So, yeah, in general, it's, it's a plus.
01:58:40Blue light glasses.
01:58:42Yeah.
01:58:44Uh, you, you mean yellow, uh, blue light blocking glasses?
01:58:50Um, I prefer to turn down the brightness of the lights at night and have a TV that's not so bright.
01:58:56But yes, I think they were much more fashionable five years ago, but I still use them.
01:59:02So yes, but definitely in general, watch out for bright light at night, but try to get
01:59:08violet and blue light in the morning.
01:59:10It's very important.
01:59:11A friend of mine in Japan found that if you don't see violet light, uh, and you're a mouse,
01:59:16you get, uh, short sightedness.
01:59:19So early morning light can be, uh, protective, like for your eyes.
01:59:24Yeah.
01:59:24Yeah.
01:59:25And we live indoors and we, we don't get enough of it from LEDs.
01:59:27Okay.
01:59:28Glucose monitors.
01:59:29Love them.
01:59:30They're really good.
01:59:31Yeah.
01:59:31I, I, I think that we should all be empowered by our own data.
01:59:35Um, anyone who says, I don't want to know about my biology.
01:59:38I think I don't agree with that.
01:59:41The CGMs have been very useful.
01:59:44Personally, I can see how I react to foods and I was surprised.
01:59:48Um, grapes send me through the roof, white rice through the roof.
01:59:51I remember the grape thing.
01:59:53Yeah.
01:59:54And it's still true.
01:59:55I'm wearing one right now.
01:59:56I wear them fairly regularly.
01:59:58The other thing that surprised me about CGMs was I gave one to my son who at the time was,
02:00:04I think 17.
02:00:06And we had a competition who can, uh, have the best blood glucose levels.
02:00:11And he would eat a lot of bad stuff.
02:00:14It changed his life.
02:00:15He is eating much healthier.
02:00:16He's now aware of what food does to his body.
02:00:19Now I'm not saying go give it to children, but I do think there's an education and a behavioral
02:00:23change that can come with CGMs that, as I think you mentioned earlier today, can really,
02:00:28really make a difference.
02:00:30Therapy.
02:00:31You mean just general, uh, psychology?
02:00:34Talk therapy, psychotherapy.
02:00:37Well, I think it depends on the person and the therapist.
02:00:41Um, I think that talking about your problems can really help.
02:00:45Um, I think it can be overused, um, as a friend.
02:00:49Um, I've, I've tried everything.
02:00:51Um, I didn't find a lot of the therapists to be that useful.
02:00:56I found it better to read books and listen to experts and, um, but I do think therapy is
02:01:01very important.
02:01:02I've, um, had kids that benefited from therapy.
02:01:05It's very hard being a teenager these days, uh, with the pressures.
02:01:09So yeah, a thumbs up for therapy though.
02:01:12Make sure you have a therapist that is well qualified and provides benefits rather than
02:01:17just listens to your complaints.
02:01:19Grounding.
02:01:21What do you mean?
02:01:21Grounding, uh, walking on grass, negative electric discharge.
02:01:28I don't think that's scientifically based, but I do think getting out in nature and
02:01:34touching, uh, nature, smelling nature, listening to nature is very valuable.
02:01:40And our body will turn out to respond in ways that we don't even understand yet.
02:01:46Marriage.
02:01:48Be careful who you marry.
02:01:50Um, know that it's not always forever.
02:01:55Know that people change over decades.
02:01:59Um, know that it's a long-term investment.
02:02:04Be loyal, never lie.
02:02:06And if kids are involved, try to work it out.
02:02:10Mouth taping.
02:02:12And, uh, mouth taping.
02:02:13Uh, so I, I do snore if I, uh, have a thick pillow or eat certain supplements at night.
02:02:22I've found.
02:02:23So I have tried mouth taping and Serena says, I make even more noises.
02:02:32Gasping.
02:02:33So I don't use mouth tape.
02:02:34I, I do use those nose strips because she thinks they help.
02:02:38Yeah.
02:02:38But no, I haven't had success myself with mouth taping.
02:02:42Testosterone therapy.
02:02:43Uh, I prefer natural versions.
02:02:46If you can't raise it naturally.
02:02:48Yeah.
02:02:49For older people, there's been a lot of benefits.
02:02:51Um, I mentioned Shelley Basin as a scientist that's worked on NMN.
02:02:55He's also done a lot of testosterone work, which shows benefits, but it doesn't extend lifespan.
02:02:59There was no evidence that it does that for longevity.
02:03:01How do you talk to a lot today about supplements, lifestyle interventions, breast recovery, what
02:03:07the future is going to look like, AI, GLPs, something that we never got to talk about when
02:03:12me, me and you first sat down with the perils of over optimization.
02:03:16I think that it was so frontier E in 2019, everything was new and exciting and you couldn't
02:03:24really be drowning in data in the same way as you can now.
02:03:27And I wonder what you've come to believe about
02:03:35the negative health implications of caring too much about your health,
02:03:40of over optimizing the neuroticism, taking away not only your enjoyment from life, but
02:03:45the effects of supposedly all of the interventions that you're actually trying to do.
02:03:50How do you come to think about over optimization?
02:03:53Well, obsession about anything is possible and also deleterious to health.
02:03:58So if you have those tendencies, be careful.
02:04:01You know, it's true for anything, social media use as well.
02:04:05And I can be obsessed.
02:04:07What I've done myself, which I recommend is treat it like a hobby.
02:04:12It's fun.
02:04:12It's not too serious.
02:04:14You're not going to die if you didn't sleep well last night.
02:04:17And everything's a challenge.
02:04:22My meals are an experiment.
02:04:25Not always.
02:04:26Sometimes it's a failed experiment.
02:04:29But I live my life like it's a journey and it's fun and I'm testing things.
02:04:36And so don't get too obsessed if you are not perfect when none of us are ever perfect.
02:04:42And none of us are going to live forever, in my opinion.
02:04:45So enjoy the journey.
02:04:46Do as best you can.
02:04:47Don't stress.
02:04:49Heck yeah.
02:04:49David Sinclair, ladies and gentlemen.
02:04:50David, you're awesome.
02:04:51I appreciate you.
02:04:52Seven years later.
02:04:53Why should people go to check out everything that you've got going on?
02:04:55Oh, well, the big one is lifespan.com.
02:04:58Become a member.
02:04:59Get the magazine.
02:05:00Learn how to live longer.
02:05:01And we'll learn together.
02:05:02We'll do some big things together.
02:05:04And I'm on social media.
02:05:07You can see what I do.
02:05:07Podcast season?
02:05:08Podcast is big.
02:05:09So that's on YouTube and all podcast.
02:05:12That's called Lifespan with Dr. David Sinclair.
02:05:16We're building.
02:05:17We're about half a million followers.
02:05:19Not like you, but we'll get there.
02:05:20You're doing good.
02:05:21We did take some time off to do the trials, but we're back.
02:05:23And even better now.
02:05:25So join us there too.
02:05:26Thank you, Chris.
02:05:27Appreciate you, mate.
02:05:28Likewise.
02:05:28Until next time.
02:05:29All right.
02:05:29Goodbye, my beauties.
02:05:30Dude.
02:05:31Yes.
02:05:31So good.
02:05:32Congratulations.
02:05:33You made it to the end of a podcast episode without dying.
02:05:36Now, here's another one.
02:05:39Go on.
02:05:40Watch it.
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