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

1. 0:00 – 0:58

   How David’s Work Has Evolved

   1. CWChris Williamson0:00

      The first ever podcast episode that I recorded in America was with you.

   2. DSDr. David Sinclair0:05

      Yeah.

   3. CWChris Williamson0:06

      In 2019.

   4. DSDr. David Sinclair0:07

      Yeah.

   5. CWChris Williamson0:08

      Harvard Medical School, in your office with what looked like the illustration of a snail on the whiteboard, and it was filmed on two iPhones, one of which I'd had to borrow from a friend, and a single white USB microphone, and that was over seven years ago.

   6. DSDr. David Sinclair0:23

      Yeah, I remember-

   7. CWChris Williamson0:23

      And now here we are

   8. DSDr. David Sinclair0:24

      ... remember it well. Uh, when you were 12, right?

   9. CWChris Williamson0:26

      I was 12. Yeah, correct. Yeah.

   10. DSDr. David Sinclair0:28

       Uh, it was very clear in, from those days that you were gonna be a big success. You were smart, driven, came prepared. Uh, and look, this is beautiful now.

   11. CWChris Williamson0:38

       Full circle. Yeah, I had... I didn't realize, uh, Starbucks Venti has way more caffeine in than the British equivalent, and it took my fucking face off. [chuckles] And I was sat opposite you trying to think about Yamanaka factors and how important NAD and resveratrol in, in yogurt is. Meanwhile, um, my whole body was vibrating.

2. 0:58 – 5:53

   Can Scientists Actually Reverse Blindness?

   1. CWChris Williamson0:58

      But, you know, you've done maybe more than almost anyone to make the biology of reversing aging a part of mainstream conversation. So I want to talk about kind of everything that's happened since we first sat down, you know, the Yamanaka factors, what's happening with NAD and resveratrol, new discoveries. Like-

   2. DSDr. David Sinclair1:16

      Right

   3. CWChris Williamson1:16

      ... before we get into that, though, what discoveries have excited you most since 2019?

   4. DSDr. David Sinclair1:23

      Gee, uh, a lot. I, I'm very lucky to have a lab where there's up to 40 people running around making discoveries. I go back there to recharge. It's a, it's like a Willy Wonka. You've been there, so you know what it's like. It's unparalleled. I wish every- wish everyone could come visit. Um, the highlights would be... So in 2020, we published on the cover of Nature magazine that we could reverse aging safely in an animal for the first time, a mouse. We cured its blindness. That was pretty big. Cover of Nature, it's what most scientists dream of in their lifetime. So that was a pretty big high. Since then, uh, it's been rewarding to see that it's been repeated not just by other labs, but in different animals, monkeys. It's been working in different tissues, so it's not just the eye anymore where we first tested it. It's pretty much working in, in every part of the animal's body. And then the big thing is we've now gone into people. So there are people getting their, hopefully their age reversed in their eye to cure their blindness, or at least improve their vision at the very least.

   5. CWChris Williamson2:31

      Why start in the eye?

   6. DSDr. David Sinclair2:33

      Yeah, good question. Um, this is a gene therapy, so we're introducing genes that are very powerful. They're called Yamanaka factors, you mentioned them, and but we use a, a subset of them that don't cause any trouble. If you just use what Professor Yamanaka used, it's not gonna be very healthy. It's, it's actually quite dangerous. So we use a subset of those, and we deliver them with a little virus-like particle, and the safest way to deliver a virus-like particle into a human is to go into a space that's enclosed, it's not gonna spread. Um, and, uh, the eye is where it's most been tested. And so we're-- we did it for safety reasons, not because it would work better in the eye. In fact, I told my student at the time, Juan Chang, that he was crazy to try to cure blindness. Why not do something easier like the liver? But he said, you know, the eye is, is probably the best place to start for safety reasons, and he was right.

   7. CWChris Williamson3:24

      Mm. I remember that, though. That was-- We were talking about that in 2019 when I was in your lab. What has... Th- there's been this recent release that came out last month. What's that? Why is that so special?

   8. DSDr. David Sinclair3:41

      The one about that we've gone into humans?

   9. CWChris Williamson3:42

      Mm-hmm.

   10. DSDr. David Sinclair3:43

       Uh, well, I think most people thought the aging field was a lot w- a lot further behind. You know, age reversal you see online, "Oh, we've done this in human cells. We've done it in a mouse," but suddenly there are people now getting what could be the world's first true age reversal drug.

   11. CWChris Williamson4:01

       Mm.

   12. DSDr. David Sinclair4:01

       So for us, it was old news. We, we'd been doing this and expecting it for a while. In fact, we made the discovery back, uh, in two thousand sixteen, seventeen. So it's, for us, it wasn't so, so amazing.

   13. CWChris Williamson4:13

       Mm.

   14. DSDr. David Sinclair4:13

       But for the world, I think it was a shock to hear that people are actually getting this potentially age reversal drug for the first time.

   15. CWChris Williamson4:19

       What would be the issue that somebody has in their eye which would be reversed? What's the, the sort of patient that this would take?

   16. DSDr. David Sinclair4:25

       Well, so this is the, the thing that makes me super excited is that every piece of d- or type of damage and disease that's, that's been tested in animals, uh, not just mice, but larger animals, it's worked to improve the vision of either a disease or damage. So for instance, if you pinch the nerve, uh, you laser it, or you give a mouse glaucoma, pressure in the eye, uh, we can treat that effectively. And nothing reverses blindness currently except for this treatment in animals even. And so that's what's exciting. Even macular degeneration, uh, glaucoma, the two leading causes of blindness in the world, both of them are really, really easily treated by this, uh, new, uh, mechanism. We call the drug ER100, which is Epigenetic Reversal 100.

   17. CWChris Williamson5:15

       Mm-hmm.

   18. DSDr. David Sinclair5:15

       Um, but yeah, pretty much any disease or injury could theoretically be fixed, treated, uh, by this technology.

   19. CWChris Williamson5:24

       Any theor- theoretically any disease or injury could be treated by this?

   20. DSDr. David Sinclair5:28

       Well, in the eye, um, but even beyond that, the liver, motor neurons, so ALS, uh, the brain has been reversed in aging, memory comes back, uh, even joints. There was a Chinese study that came out recently, looked very good. You-- They used our technology to rebuild bone and cartilage in, in, uh, osteoarthritis. And so, you know, I don't know anything else that just rebuilds body parts

3. 5:53 – 8:57

   How Does ER100 Work?

   1. DSDr. David Sinclair5:53

      like this.

   2. CWChris Williamson5:53

      Can you explain how it works to a simpleton?

   3. DSDr. David Sinclair5:57

      Uh, not you, but, uh, I don't think anybody listening is a simpleton, but it- it's actually quite simple, the, the good news. We take three genes that are normally turned on early in life. And these three genes make factors that turn on a cascade of, of events that the cell uses to reboot itself. The simple way to think of it is that I hypothesize that the body has software that gets corrupted as we get older. So an old person still has information there, it's just that it's been corrupted, the software. We call that the epigenome. It's separate from the genome, which is the DNA. The epigenome sits on top of that and controls the DNA. So in, in my book, Lifespan, it's a little dated now, but you might remember I chose a CD as the analogy. The epigenome is the reader of the music, and the DNA is the music itself, and aging is a scratched CD. So for those listeners and viewers who don't really know what a CD is, they were really cool things we could put 20 songs on. But a better analogy now would be your phone has software. You know, a really old phone is slow. It can be corrupted, can get o- you know, over- overused. Um, and so we can reboot that. And we, we found that these three genes that we put in, which we call O, S, and K for short, these Yamanaka genes, trigger a program that embryos normally use to reset their age or something very similar to that program.

   4. CWChris Williamson7:24

      Hmm.

   5. DSDr. David Sinclair7:25

      Um, something you might not know, most people don't know this, is that when we're fertilized, and we've all been fertilized, we wouldn't exist, and then we need to reset this epigenome. The software needs a reset to go back to being young again, and that happens-

   6. CWChris Williamson7:38

      No way.

   7. DSDr. David Sinclair7:39

      It's, it's a fact. It's shocking but true. Young, very young embryos are old, and then they get reset. So the, the software is really... It's not software, it's the way the DNA is folded in the cell, and every cell has to compact the DNA 'cause it's six feet long, has to fit into a microscopic little, little ball. And, uh, how that's compacted depends on what kind of cell you're gonna get. So if you want to make a nerve cell, you compact different genes, and when you compact them, they switch off.

   8. CWChris Williamson8:08

      Hmm.

   9. DSDr. David Sinclair8:08

      But you need to read nerves that make nerve cells, so you open those up. And this, this bundling and opening of DNA is what the epigenome does. And my theory, called the Information Theory of Aging, said that this pattern, pattern of bundle loop, bundle loop, which is different for every cell type, gets corrupted, gets eroded during aging, and that literally is aging.

   10. CWChris Williamson8:31

       Mm-hmm.

   11. DSDr. David Sinclair8:31

       And we tested this and published it in 2023, and we created a mouse where we could disrupt those loops and bundles, and the mouse's cells lost their function. They lost their identity. The nerve cells forgot how to be nerve cells, uh, and the mouse literally got old. We could speed up that process by corrupting that software, the epigenetic software. And then when we did that, which took us 13 years, uh, we started working on reversing that process, which is how we get

4. 8:57 – 10:14

   Is Aging a Disease?

   1. DSDr. David Sinclair8:57

      to here.

   2. CWChris Williamson8:57

      Yeah, people see aging as a certainty, but you call it a disease. Is it truly a disease, or is that just a useful metaphor?

   3. DSDr. David Sinclair9:06

      Well, it's just a word really [chuckles] , so we can call aging whatever we want, but I prefer to think of aging as a disease because otherwise we're not really treating it. Most doctors don't think of old age as something that is preventable or treatable, even though now we, we believe we understand that it is very treatable-

   4. CWChris Williamson9:23

      Mm

   5. DSDr. David Sinclair9:23

      ... uh, or at least slowable. Um, so I think it's a useful way to look at aging as something that we should address, um, even starting early in life to try to slow it down at least. Um, we all need to stick around for longer 'cause the technology that's coming is incredible. Um, and I proposed this in my book and, uh, even put it on the back cover and, uh, it was... A lot of people were telling me that that's crazy. "Don't say that, David. It's gonna be scandalous. People are gonna not take you seriously as a scientist." Um, but I'm glad, uh, Matt, my co-author, Matt LaPlante, convinced me we should go for it. Actually, that was his main role besides writing was to say, "David-

   6. CWChris Williamson10:03

      Go for it

   7. DSDr. David Sinclair10:03

      ... just do it 'cause don't worry what your colleagues will say," 'cause some of them can be pretty brutal. So we put it in there and, uh, and it's seemingly been embraced by a lot of people, and now you hear it

5. 10:14 – 14:01

   What’s Next in Age Reversal?

   1. DSDr. David Sinclair10:14

      quite often.

   2. CWChris Williamson10:15

      What's the technology that's coming? If that's what we've done so far-

   3. DSDr. David Sinclair10:17

      Mm-hmm

   4. CWChris Williamson10:18

      ... what do the next few years have in store for us?

   5. DSDr. David Sinclair10:22

      Well, there's a fork in the road. I don't know when it's coming, but it's similar to the singularity with AI or, or AGI. We... When we show, and it's a matter of when, not if, that aging is reversible in humans, 'cause it works in all these other animals, it'll work in us. We're basically just slightly more intelligent monkeys, and it works fine in, in the monkeys. That's gonna be a turning point, I believe, for humanity. There'll be a lot of people who say, "All right. Now let's get on board. Let's invest. Let's blow this out of the water." There's already a lot of billions of dollars put into this, but it's gonna, gonna be big like AI when that happens. But these technologies, let's say it works in the eye and now we can treat, perhaps cure most types of blindness, then we're gonna... We're already doing this. I should... You know, I can't talk about too much, but we're already looking at other tissues, the liver, for example, and maybe there's joints and hearing that we can also repair. Ultimately, where this is going, obviously, is whole body reset. Um, and we can do this in mice easily in my lab now w- and others have done this and they live longer.

   6. CWChris Williamson11:31

      Every cell in a single organism?

   7. DSDr. David Sinclair11:33

      Uh, well, we don't have the technology with the viruses and the genes to reset every cell, and that's a limitation of getting the genes into every cell. We can't do that. You can-- We can basically at best get it into half of the cells, but still a lot of them.

   8. CWChris Williamson11:48

      Mm-hmm.

   9. DSDr. David Sinclair11:49

      Um, we've taken a, a path that's a little different now. You know how I was saying we've been doing this for a while, and the world doesn't really know what we're up to in my lab. Um, I can reveal that over the last five years we've made breakthroughs in turning it into a pill. That's the next big thing that'll come out of my lab, is revealing that we can give a mouse, an old mouse something orally. So we-- They don't chew on the pill. We give it down their throat for- Three days a week for a month, uh, and we see that they are, uh, uh, rejuvenated in many ways, including, um, not just their memory, but things like even their skin quality

   10. CWChris Williamson12:25

       What does... What, what's happening? What, what's the pill doing to them?

   11. DSDr. David Sinclair12:28

       Well, that's a lot of work. Uh, we're still trying to figure that out, but we-

   12. CWChris Williamson12:31

       So you know it works-

   13. DSDr. David Sinclair12:33

       Well, we know it works

   14. CWChris Williamson12:33

       ... but you don't necessarily know why or how it works.

   15. DSDr. David Sinclair12:35

       Well, we, we actually literally don't know how the genes that are in the eye of humans now work really. That's a big question in, in my lab, uh, is trying to answer: where is this backup copy of software? Um, but we do know it works. That's the hard part. And then figuring out how it works will be important to make these drugs even better and more powerful and more potent and longer lasting. But what we do know is that the epigenome is involved in the pill, uh, not just in the gene therapy, because we can disrupt that, uh, polishing of the CD or the reset of the software.

   16. CWChris Williamson13:07

       Mm.

   17. DSDr. David Sinclair13:07

       Um, there are genes called TETS, uh, which make proteins that strip, uh, away chemicals off DNA. These are key to the epigenome reset in embryos as well as in our bodies. And we can get rid of them or inhibit them with a chemical. Um, and we can feed those to the mice or give it to the cells, and we have some good evidence, um, I hope my students don't kill me for saying this publicly, but we do have good evidence that the pill, let's call it, the cocktail, does work through this epigenetic thing. It's not just, oh, the cells are getting stressed out by the chemicals, and they fight back and they live longer. It's, it's not that. It's truly through this reset mechanism, and we can show that-

   18. CWChris Williamson13:50

       Mm

   19. DSDr. David Sinclair13:51

       ... by getting rid of these TET enzymes that strip chemicals off the DNA. And without that mechanism, the cells don't get younger, even with the chemicals.

6. 14:01 – 17:10

   How to Reverse Aging Without Going Too Far

   1. CWChris Williamson14:01

      Do you think there's gonna be a realistic upper bound to human life?

   2. DSDr. David Sinclair14:04

      Uh, well, the question is when. Uh, I think that ultimately there is no upper limit to human life. There are-- I just visited a bonsai garden in Japan where the trees are a thousand years old, and that's... They're not even halfway through their life. So biology doesn't have limits. It's just a question of what our genome encodes and our epigenome. But, you know, we have control this century over our own biology. We don't have to just be at the whim of what evolution and the Serengeti gave us. And I see... And no upper limit doesn't mean I think you and I will be immortals. That's right now beyond our imagination. Well, it's definitely imagination, but it's beyond technology-

   3. CWChris Williamson14:42

      Mm

   4. DSDr. David Sinclair14:42

      ... that I can think of. Uh, but I do think that some of us will have a chance to live decades longer, and probably the first person to live to a hundred and fifty is already alive.

   5. CWChris Williamson14:54

      First person to live to a hundred and fifty is already alive?

   6. DSDr. David Sinclair14:56

      Yeah. I'm, I'm not the only one in my field saying that. It's, it's now realistic. I mean, think about it this way. W- It's hard to imagine the future, right? But the p- a kid born today is gonna live into the twenty-second century, and we can't even imagine what the world's gonna be like ten years from now.

   7. CWChris Williamson15:12

      Mm-hmm.

   8. DSDr. David Sinclair15:13

      So the longer you live, actually, the longer you get to live.

   9. CWChris Williamson15:17

      Surely, if someone took age reversal pills for long enough, they'd just become a baby. Is that not the way it works?

   10. DSDr. David Sinclair15:22

       Well, we, we made sure that wouldn't happen. That was one of the, the things that Wan Chang, my student-

   11. CWChris Williamson15:26

       You Benjamin Button everybody into a-

   12. DSDr. David Sinclair15:28

       Yeah. Well, that was the trick

   13. CWChris Williamson15:29

       ... embryonic death.

   14. DSDr. David Sinclair15:30

       Okay. Yamanaka, um, Professor Yamanaka won the Nobel Prize for making cells go back to age zero and making them into stem cells, but that's not gonna help us. We don't want to strip away the identity of all our cells. We'd die within a, a couple of days. And, and in fact, if you do that to an animal, it tra- it tragically does die or gets, gets cancer. So what took us the longest time from two thousand and fourteen to two thousand seventeen was figuring out how to reverse aging, but not so much that it loses the identity of the cell-

   15. CWChris Williamson16:01

       Mm

   16. DSDr. David Sinclair16:01

       ... or erases it. And my student, Wan Chang, uh, famously almost quit the project. He was doing his PhD. He was in his last year, and nothing was working. He was either having no effect on the human cells in the dish, or they would be becoming cancerous. And he said, "David, I, I don't know how to stop it halfway." And we came up with one last experiment that, thank goodness it works, 'cause we, you know, wouldn't be talking about it now. Um, we tried a subset, just three of the Yamanaka genes, and leaving one of these Yamanaka genes out was key. Without that final gene, it's called cMyc, we call it M. Without M, the M gene, cells don't go back a hundred percent. They go back about seventy-five and stop.

   17. CWChris Williamson16:45

       Mm.

   18. DSDr. David Sinclair16:45

       And, and that was the breakthrough. The stop was really hard to find, uh, but it's there. And it's one of the reasons-

   19. CWChris Williamson16:51

       Or else it'd just turn everything into stem cells.

   20. DSDr. David Sinclair16:53

       Yeah, yeah, or cancer. It's even worse. Um, well, maybe not, not worse, but it's definitely bad.

   21. CWChris Williamson16:58

       Mm.

   22. DSDr. David Sinclair16:58

       You're not gonna live longer or cure blindness.

   23. CWChris Williamson17:00

       Mm-hmm.

   24. DSDr. David Sinclair17:00

       But that was a breakthrough, and, and Wan Chang sent me the pictures of the cells that were younger and said, "Eureka, I think we've done it," and it, it was a remarkable thing to witness.

7. 17:10 – 20:40

   What Most Longevity Experts Secretly Believe

   1. CWChris Williamson17:10

      What do you think most longevity experts secretly believe but can't prove or won't say publicly at the moment?

   2. DSDr. David Sinclair17:17

      Gosh, that's a good question. I was gonna say most of them secretly think that I hype this stuff way, way more than I should, which is, again, a, not a fair thing 'cause my lab is eight years ahead of what we've published. Um, but I think most s- most aging researchers, I can say for a fact behind the scenes, say, "This is gonna be much bigger and more powerful than we expected." Uh, I've been told by some of my colleagues, "Don't say that number a hundred and fifty. It makes us look bad," you know? And I'll say, "Well, do you believe in it?" "Yeah, but we can't say that 'cause we're scientists, and we'll lose credibility."

   3. CWChris Williamson17:52

      Mm.

   4. DSDr. David Sinclair17:52

      So yeah, I think a lot of the scienc- scientists are very cautious by nature, by the profession. I'm considered an outlier speaking my mind and what I believe in, but most scientists don't 'cause it, uh, it's not something scientists typically do.

   5. CWChris Williamson18:06

      Mm. Why is it that you're seen as an outsider? Are, are you throwing more caution to the wind than other people? Is it that their criteria for, uh, evidence is, is different to yours? Is it that your lab has got access to information that other people don't?

   6. DSDr. David Sinclair18:26

      Well, there's a few reasons. It's definitely that my lab has information that nobody else knows, and that's been, uh, difficult my whole career, knowing that something's true but it's not published yet. So in the minds of my colleagues, it doesn't exist yet. And in fact, my book came out s- in some cases years before we published the work. So the public knew my lab's work before other colleagues had seen it. Um, that's also rare. Another reason why, uh, I'm a bit of an outsider is, um, I'm not doing this to be a scientist. I'm doing this because I'm on a mission, and my life is irrelevant. Um, I would literally die to achieve this mission. And so, you know, if I get criticized or if I speak my mind, I real- really don't care. It's-

   7. CWChris Williamson19:11

      What's the mission?

   8. DSDr. David Sinclair19:12

      Uh, to impact in a positive way as many lives as possible. Um, this was since I was, uh, four years old. My grandmother gave that mission to me 'cause she lived through World War II and the aftermath in Europe and, uh, she told me the horrific things that humans did and can do, and she was always saying we can do better as a species. And I feel like, uh, I want to die knowing that I've done the most for humanity that I could possibly do. And, and if it upsets a few people, I don't care.

   9. CWChris Williamson19:45

      I've learned from over a thousand podcast episodes, the easier that you make your health routine, the more consistent you'll be. It's like golf, right? You want to keep it simple and not mix a bunch of pills. You want the eye of the tiger, not the DUI of the tiger. That's why I'm such a huge fan of AG1. One scoop contains seventy-five vitamins, minerals, probiotics, and whole food source ingredients in a single daily drink, and that's why I've been taking it every single morning for nearly five years now. And they've taken it a step further with AG1 Next Gen, backed by four clinical trials. In those trials, it was shown to fill common nutrient gaps, improve key nutrient levels in just three months, and increase healthy gut bacteria by ten times, even in people who already eat well. Plus, if you're still unsure, they've got a ninety-day money-back guarantee, so you can buy it and try it every single day for three months. And if you don't like it, they will give you all of your money back. Right now, you can get twenty percent off a welcome kit and that ninety-day money-back guarantee by going to the link in the description below or heading to drinkag1.com/modernwisdom. That's drinkag1.com/modernwisdom.

8. 20:40 – 22:45

   The Biggest Levers for Reversing Aging

   1. CWChris Williamson20:40

      Longevity is a huge field, right? It includes everything. When you think about all of the different types of interventions that people can do, how do you chunk them into groups? Sort of what are the buckets that people should be thinking about as contributing to their-

   2. DSDr. David Sinclair20:53

      Yeah

   3. CWChris Williamson20:54

      ... lifespan?

   4. DSDr. David Sinclair20:55

      Yeah, so I talk about this on, on my YouTube as well. So there's a lot of detail on there now, and I've relaunched it. It's really disgusting.

   5. CWChris Williamson21:00

      Congratulations. Welcome back into the fray.

   6. DSDr. David Sinclair21:02

      Thanks.

   7. CWChris Williamson21:02

      I'm glad that you've stopped doing the wasteful work in your lab and gone into the serious work of YouTube videos.

   8. DSDr. David Sinclair21:07

      Yeah. I was, uh, working on, uh, solving aging and now, now that the clinical trials have started, I'm back to more important-

   9. CWChris Williamson21:13

      Back to being an influencer

   10. DSDr. David Sinclair21:13

       ... more important things.

   11. CWChris Williamson21:14

       Mm-hmm.

   12. DSDr. David Sinclair21:15

       Uh, but yeah, so what we talk about on the podcast is what are the, the major things that people can do to slow down aging and even reverse aspects of it.

   13. CWChris Williamson21:23

       But if we've got this technology coming soon-

   14. DSDr. David Sinclair21:25

       Yeah

   15. CWChris Williamson21:25

       ... you're eight years ahead, everybody is doing the longevity escape velocity bet, right? For every day that I live, there's more days that I can hopefully live. So in the interim, those are the buckets, right? That's the stuff that people need to focus on now.

   16. DSDr. David Sinclair21:37

       For sure. I think anyone that doesn't focus on their longevity, uh, might miss the boat. Um, it'd be tragic if you, you died a few days before, you know, some of these technologies came out. And this is... I'm not worried about you killing over anytime soon. You're very fit. Um, but you know, your parents, your grandparents, think about them. So try to encourage them to live the healthy lifestyle that we're, we're going to discuss now. The buckets are, uh, lifestyle. So within that, there's the obvious things we can talk about, which is what you eat, how you move, how you rest, your stress, these kind of things. That's what you can do and you should do on a daily basis. It's what I do. Then there's, uh, drugs, which some of which may work, so that's metformin, rapamycin, some senolytics, and probably GLP-1 receptor agonists would fall into that bucket. Um, and then there's supplements, which is the Wild West. There's a lot of things said about them. Um, I believe in a few of them based on a lot of animal research and some human data.

   17. CWChris Williamson22:38

       Mm.

   18. DSDr. David Sinclair22:38

       Uh, those are the three main things, uh, that you should do in your daily life to maximize your chance of getting these medicines.

9. 22:45 – 32:47

   Can We Survive 2 Weeks Without Food?

   1. CWChris Williamson22:45

      Okay. Lifestyle stuff.

   2. DSDr. David Sinclair22:46

      Yeah.

   3. CWChris Williamson22:46

      Last time that we were talking, it was all about calorie restriction and primarily fasting as a route toward calorie restriction. How should people eat if they want to live as long as possible now-

   4. DSDr. David Sinclair22:59

      Yeah

   5. CWChris Williamson22:59

      ... with your twenty twenty-six data?

   6. DSDr. David Sinclair23:01

      Well, actually what I've been saying, uh, actually on, on my podcast for now, what, four years, uh, it hasn't changed. And my book, Lifespan, which came out, we were talking about when we first met in two thousand and nineteen, it... Nothing in that book I've had to revise. It's all consistent.

   7. CWChris Williamson23:16

      So there's no retractions from the book in twenty nineteen?

   8. DSDr. David Sinclair23:18

      No. No, and my lab's never retracted anything and at this point never been proven wrong, which is a blessing and I knock on, touch on wood. But that's good news, which means that the things that I've said before, people can go back and learn still. Um, if this is the first time you're seeing me, uh, you know, let's, let's start. So the, the main things about fasting are we know from animals, um, and some human data, but mostly from animals, that if you restrict how often you eat, um, and to some extent how much you eat, you get longevity benefits. Um, and we can talk about protein ratio to carbs to fats. That's also a whole big debate, as you know. But generally, I, I like to eat one meal a day, maybe two if I'm being social, but not three. I think three meals a day plus snacks is marketing. Um, breakfast being the most important meal of the day was General Mills, I believe, uh, one of those companies, Kellogg's perhaps. But, uh, this is, you know, it's all marketing. Humans are not built to eat that consistently. I don't think cavemen were sitting around eating their big breakfast saying, "What are we going to eat for lunch?" I think, you know, maybe if they just killed a mammoth, but generally they were pretty hungry a lot of the time, and our bodies have adapted to that. We're not meant to always be satisfied. Um, and so I try to be hungry and if I gain a little bit, bit of weight, sometimes I travel and I eat well and Serena and I, uh, we do, uh, sometimes love to eat. I'll come home from travel and just I won't eat for three days. Sometimes two weeks I can go without food. It's not a big deal for me.

   9. CWChris Williamson24:51

      Two weeks without food?

   10. DSDr. David Sinclair24:53

       Yeah. Okay. I might munch on a, on a piece of celery or something, but that's not really nutrition. I will drink a lot. I'll drink a lot of low-calorie, zero-calorie drinks, a lot of tea, that kind of stuff, but I can go without food for two weeks. It feels great. After the first three days, I'm over the hunger feeling. Um, I can see on my monitor, which I've got one on here.

   11. CWChris Williamson25:15

       CGM.

   12. DSDr. David Sinclair25:16

       Uh, the CGM. Yep. Uh, I can see the great impact it's had, having on my body. I can monitor it on my rings. I do blood tests, which is important. You don't wanna just guess what's working, what isn't. But yeah, I know two weeks sounds like a lot, but-

   13. CWChris Williamson25:30

       It is a lot. It's like-

   14. DSDr. David Sinclair25:31

       I feel great

   15. CWChris Williamson25:31

       ... it doesn't sound like a lot, it is a lot.

   16. DSDr. David Sinclair25:33

       It is a lot. And I'm a regular guy. I, I st- I'm not like some people that spend millions of dollars on their body and, and measure everything. I'm kind of lazy. I, I don't like being hungry. I like food. I like to snack. I, I like to stay up late. I'm a typical hedonist, if you let me go. Um, and actually, up until a year ago, I actually hadn't fasted more than 24 hours. I just couldn't do it. It's like, this is painful. Um, and I'm stressed, so if I'm stressed, I'm gonna eat. Um, but what I've learned over this past year is I can go beyond 24 hours, and once I'm over three days, something kicks in. Actually, we know molecularly there's something called chaperone mediated autophagy or CMA, which is the deep cleanse of these misfolded and modified proteins that you wanna get rid of for aging-

   17. CWChris Williamson26:18

       Hmm

   18. DSDr. David Sinclair26:18

       ... or slowing aging. And, uh, after those three days, you know, I, I start to feel amazing. My mind clears. Um, I don't feel bloated at all. Um, I don't even have to go to the toilet that often, except for all the tea, but you know what I mean. And, uh, yeah, I feel energized. And I, I'm measuring myself, so I'm making sure I'm not overdoing it. This is not for everybody. If you're skinny and you've got barely any fat or you're elderly, it's not for you. But for me, I gain weight and muscle pretty easily. I can fluctuate. And so I watch my weight come down. I've got, uh, a scale that measures my weight. Um, it's... I don't know if I can measure, uh, say the name or if it- it's-

   19. CWChris Williamson26:57

       Mm-hmm

   20. DSDr. David Sinclair26:57

       ... forbidden, but, um, I do like the Withings scale 'cause it-

   21. CWChris Williamson27:00

       Smart scale links to the phone.

   22. DSDr. David Sinclair27:02

       Yeah.

   23. CWChris Williamson27:02

       It will get you composition as well if you hold the handle.

   24. DSDr. David Sinclair27:04

       Yeah. And, and I've had one since 2013, so I've got all this data on my body weight and composition, which is awesome, and I'm trying to maintain that at the optimal level over these last 13 years.

   25. CWChris Williamson27:14

       What are you... Um, this two weeks thing is blowing my mind. What are you running on after 10 days? Are you... Why is malnutrition... Are you supplementing with, with vitamins-

   26. DSDr. David Sinclair27:22

       Oh, yeah

   27. CWChris Williamson27:22

       ... and stuff so that you don't get scurvy? Like why are you not dropping dead?

   28. DSDr. David Sinclair27:26

       Yes, I am. I am. No, I'm glad you said that, Chris, 'cause it's important to say I'm a scientist about this. I'm not just willy-nilly giving up everything.

   29. CWChris Williamson27:32

       Two celery and green tea, surviving for two weeks, just bro science-ing it. Yeah.

   30. DSDr. David Sinclair27:36

       Well, no, I'm not doing that. I, uh... The reason I'm using my hands is I travel, and at home I have a little carry pack with vitamin supplements, um, and medicines that I've been using and know very well what I need. I... Every morning it's a symphony of supplements and medicines, actually. I know what my body needs. I know what, what works. Uh, so I do that. So there's not... Not anybody can do that. So it's really important if you do fast for long periods, make sure you... Enough hydration, very important. We know that. But also I'm making sure that I'm not deficient in any minerals or vitamins, and so I'm, I'm taking in things like vitamin D, uh, vitamin C as well, and some nutrients that I know I can become deficient in.
10. 32:47 – 35:52

    The Most Effective Way to Fast

    1. CWChris Williamson32:48

       What would you say, let's say that someone finds this quite seductive, what would be a good start? A one-day fast, a three-day fast? And what, what should they do? What would be a, a rough protocol to follow without having to be a-

    2. DSDr. David Sinclair33:02

       Yeah

    3. CWChris Williamson33:03

       ... a conductor of supplements?

    4. DSDr. David Sinclair33:05

       Yeah. Well, if, if you're, if you've never fasted and you just wake up and you eat a normal breakfast, lunch, dinner, e- either you're, you're obese or you exercise a lot 'cause that's gonna put on weight. Um, but if you are willing to try, I would suggest skipping one meal and replacing it with a lot of liquids. So for me, I, I don't mind skipping breakfast. Not everybody wants to do that 'cause they work out and they feel like they need some food. Um, so you can instead, you can skip dinner. I would just have a very early dinner. Um, what I was doing for many years, for probably 30 years of my life, was trying not to eat anything until late lunch. Um, and you, you will initially feel hungry. This is the thing. Don't give up because it takes a few days for your body to get used to not having the food. It'll be screaming at your brain, "I'm so hungry, I'm gonna die if I don't eat this bacon and eggs." Uh, but get, get through it and actually after two weeks it'll become really weird to eat food in the morning-

    5. CWChris Williamson34:08

       Mm

    6. DSDr. David Sinclair34:08

       ... or at night. Your body gets used to it, your brain gets used to it, but it does take a while. And the cheat code is fill your stomach with lots of liquids. Not sugary drinks, not a lot of, uh, of calories. Zero if you can, or just a little bit. Um, I do have a little bit of calories in the morning because it's good with my supplements, but, um, a lot of water, so a low-calorie drink like this-

    7. CWChris Williamson34:32

       Yep

    8. DSDr. David Sinclair34:32

       ... or water, tea, um, black tea. Coffee is very good. They're both good. Actually, tea and coffee are both very good for you because they contain other molecules like polyphenols that again, can activate these enzymes that protect us.

    9. CWChris Williamson34:46

       Somewhere along the way, low energy just gets accepted as a part of getting older. Turns out there's a reason for that. As we age, our mitochondria, the parts of our cells that power us, become weaker and make less energy, which is why I'm such a huge fan of Timeline. They've developed this, that helps to clear out your damaged mitochondria so your cells can actually renew themselves. Timeline is backed by over a decade of research and has more than 50 patents, and is the number one recommended mitochondrial supplement on the planet. This isn't just theory. In clinical trials, people saw mitochondrial renewal increased by more than 40% in just 16 weeks, along with improvements in their overall energy. I've been using it for over two years, since my doctor recommended it to me way before I partnered with Timeline, and eat your heart out, Martin Shkreli, 'cause they've just dropped the price and it now starts at $99. Best of all, there is a 30-day money back guarantee, plus free shipping in the US, plus they ship internationally, and right now you can get that $99 price with an additional 20% off by going to the link in the description below or heading to timeline.com/modernwisdom using the code MODERNWISDOM at checkout. That's timeline.com/modernwisdom and MODERNWISDOM at checkout.

11. 35:52 – 40:33

    Does Calorie Restriction Actually Extend Human Life?

    1. CWChris Williamson35:52

       Have we seen any data that shows calorie restriction increases lifespan in humans? I know that this exists in rodents.

    2. DSDr. David Sinclair36:01

       Yes. Um-

    3. CWChris Williamson36:03

       There was a study that was done, was it macaques or something? And that didn't actually work because it was a two-decade study, and the first version of the study, it turned out that they hadn't fed them the same diet and split it in half. They'd fed one of them a junk food diet and the other one had been given a healthy one. Then they ran it back and it seemed like the data was mixed there. What's the evidence about calorie restriction for longevity in humans? Is there any?

    4. DSDr. David Sinclair36:26

       Uh, no. Uh, there's a lot of anecdotal and historical evidence that fasting is good for you, and there have been some short-term studies over a couple of years. There was the calorie study that showed that you could improve a lot of health biomarkers in humans over that time. That had lasting effects, including on the epigenome. But nobody's really done a prospective study, uh, with placebo. It's very hard to do that-

    5. CWChris Williamson36:49

       Mm-hmm

    6. DSDr. David Sinclair36:49

       ... or even controls. So we-- There's no proof, and I don't think anytime soon there'll be proof. But who wants to wait another 100 years till that happens? You can't. You've got to at least go based on the evidence. And in animals it's incontrovertible that, that if you do it with nutrition, not just starving, it's very good for you. Um- And that's why I do it. I would say with the monkey study, I know it very well because the two labs that disagreed about this, one, uh, is one of my best friends and the other one is my trainee. And they were-

    7. CWChris Williamson37:23

       Oh, wow, you're like Switzerland in between the two of them

    8. DSDr. David Sinclair37:25

       ... going at it. Yeah. I didn't really get involved, um, but I did bring them together and they, they came to a- the conclusion that, yes, it did extend lifespan. Um, it depended on the, the veterinary care and other, other environmental things. The University of Wisconsin, where the other lab is, uh, Rosalind Anderson is the professor that I originally trained, what is it, twenty years ago. Uh, she runs the study now, and her monkeys lived longer, and they also definitely incontrovertible, uh, evidence that they had less cancer and I think heart disease. But definitely overall disease burden in these monkeys was lower.

    9. CWChris Williamson38:04

       Mm.

    10. DSDr. David Sinclair38:04

        And they lived slightly longer. But even if they didn't live longer, I would say still look at the data on the diseases. I mean, who wants to get cancer and heart disease in their sixties and seventies?

    11. CWChris Williamson38:15

        Why would high calorie turnover increase your likelihood of cancer and heart disease?

    12. DSDr. David Sinclair38:22

        Well, there's a few different theories. The one that I like the best that's the simplest is that when your body is in a state of perceived adversity and running, building muscle, lifting weights and hunger are signs of adversity. Um, also eating plants that are stressed is a sign to your body that your food might run out. This is put your body in adversity mode. And this enzyme that I mentioned earlier called Sirtuin, which protects the epigenome, it responds to hunger and exercise. Um, there's a molecule called NAD that a lot of your listeners and viewers would know about. This enzyme responds to NAD levels. Uh, but long story short is when you're in adversity mode, your body switches from growth and reproduction into survival mode. And at least if you do that for some of your day or some of your week, you'll get some protection against the ravages of aging. Epigenetic changes, um, DNA damage, all of these things that we know contribute to aging.

    13. CWChris Williamson39:19

        Do you think that there would be a marked difference between somebody who restricted their calories by thirty percent over a, a year, let's say, and somebody who restricted their calories by thirty percent with big breaks in food? Calorie restriction versus calorie restriction through fasting. Do you think that those two people would have different kinds of outcomes?

    14. DSDr. David Sinclair39:39

        Hmm. So are the... One is eating more than the other?

    15. CWChris Williamson39:42

        No.

    16. DSDr. David Sinclair39:42

        Sorry.

    17. CWChris Williamson39:42

        They're both eating the same amount of calories.

    18. DSDr. David Sinclair39:44

        Oh, they're isocaloric as well.

    19. CWChris Williamson39:44

        One, one... Let's say that, let's say that-

    20. DSDr. David Sinclair39:46

        Yeah

    21. CWChris Williamson39:46

        ... um, somebody has a hundred calories an hour for eighteen hours of the day, and another person has one meal that's eighteen hundred calories per day.

    22. DSDr. David Sinclair39:54

        Okay. Um, there's a lot of evidence that eating within the time window is the one that's much healthier. Um, the friend that I mentioned earlier, Rafa- Rafael de Cabo down at the NIH here in the US, what he did in, again, in mice, but I think there's a lot of evidence that it would translate to humans. He gave mice roughly the same amount of calories, but he gave it to them all day, and they had to gobble it all down quickly. It didn't matter what they were eating. It was different amounts of protein, uh, carbohydrate, fat. He was hoping to find the optimal diet, but he found that the group that ate within that window lived substantially longer than the ones that ate continuously.

12. 40:33 – 44:23

    Is the Proteinmaxxing Movement Overhyped?

    1. CWChris Williamson40:34

       I saw you quote tweet something about protein being overhyped, the Proteinmaxxing Movement. What's your position on that?

    2. DSDr. David Sinclair40:43

       Yeah. No, protein is good. Um, I'm not against protein at all. I eat a lot of protein myself actually, mostly from plants for reasons that I'll get to. Uh, but the, this diehard be a carnivore, forget about the green stuff is, is definitely not consistent with the science of longevity. It's consistent with the science of bodybuilding, and it definitely-

    3. CWChris Williamson41:04

       Which of course we know-

    4. DSDr. David Sinclair41:05

       ... definitely works

    5. CWChris Williamson41:05

       ... is a superior science.

    6. DSDr. David Sinclair41:07

       Yeah.

    7. CWChris Williamson41:07

       To the science of longevity.

    8. DSDr. David Sinclair41:08

       Exactly. Yeah.

    9. CWChris Williamson41:09

       Yeah.

    10. DSDr. David Sinclair41:09

        Well, you know, I, as much as it doesn't look like it, I really like bodybuilding over other exercise. Um, I'm just busy. I used to work out a lot. Um, I love bodybuilding, and protein is essential for building muscle, no question, okay? And you can get a lot of protein from protein supplements and meat. Where I think it's been overhyped is we know that plants are essential for providing polyphenols and having l- a lack of branched-chain amino acids specifically is also very good for health. A lot of data on that, especially in animals, but some in humans. So branched-chain amino acids, some people listening will know what they are. Valine, leucine, leucine. These are three of the twenty amino acids that are found in more abundance in animals than in plants. And when you give animals a lot of these branched-chain amino acids, uh, they live shorter than if you give them less. And this has been shown in short-term studies in humans. If you restrict protein, um, that has a lot of branched-chain amino acids in humans, they get better metabolically. But I'm not saying you can't eat meat or you can't eat protein. What I'm saying is just doing one or the other, uh, is not really the best way to live.

    11. CWChris Williamson42:20

        Mm.

    12. DSDr. David Sinclair42:21

        I think the best way is to pulse it. Okay? So if you're working out, you want to build muscle, yeah, you can eat, you can eat meat. I eat meat occasionally. It's not a problem. But you want to have a period of your life or your, let's say, your day or your week where you're not eating meat or you're just not eating. Um, and that puts your body at least part of the time in this adversity mode.

    13. CWChris Williamson42:43

        Should you be doing both? Let's say that somebody's doing OMAD or, uh, 168 or some sort of fasting protocol. Would you still be looking to pulse protein intake as well separately to that?

    14. DSDr. David Sinclair42:55

        Yeah, I... Yes. Yeah, the answer would be-

    15. CWChris Williamson42:57

        So you'd maybe go one day a week without protein as well?

    16. DSDr. David Sinclair43:01

        Well, without protein, I don't think you'll live, right? You need some protein.

    17. CWChris Williamson43:05

        Mm-hmm.

    18. DSDr. David Sinclair43:05

        But you're... You mean huge amounts of protein or you mean meat?

    19. CWChris Williamson43:08

        No, I mean, like you're saying that there's- Time for you to focus on protein-

    20. DSDr. David Sinclair43:12

        Awesome

    21. CWChris Williamson43:12

        ... and then there's time not to. You should be fasting. I'm wondering whether you should be fasting from protein from a macronutrient standpoint as well, in your opinion.

    22. DSDr. David Sinclair43:21

        I don't think so. I don't try to fast from protein. I try to fast from a lot of calories, and I also try to fast from a lot of animal protein, which has these branched-chain amino acids. And we know the molecular mechanisms. There's mTOR, which anyone who follows longevity will know about this mTOR. And if you're eating a ton of meat every meal or ev- every day, uh, your mTOR is gonna be active, and mTOR's role is to help cells divide, grow, build muscle. Great. That's what you wanna do. When you're young, you wanna build muscle, you wanna look good, you wanna be strong. Even if you're older and you have sarcopenia, mTOR is good. But we know that animals that have active mTOR live shorter than those that have less active mTOR. So how do you get the benefits of both? Well, that's what I'm saying, is have mTOR switch down, plant protein mainly, don't eat a lot. mTOR will help you when it's switched off, but you can rev it up when you wanna build muscle or, or, uh, run a marathon or something like that. You don't always have to be in one state or the other.

13. 44:23 – 47:39

    Could Sex Help You Live Longer?

    1. CWChris Williamson44:23

       Hmm. Okay, talking about exercise, has your exercise philosophy changed? What is the best exercise protocol for longevity, in your opinion?

    2. DSDr. David Sinclair44:30

       No, it hasn't changed a lot. Uh, it's... We're-- I just keep seeing studies that, that say the same thing over and over again, and then people argue about the latest one. We know that the best health is a combination of weightlifting. Uh, muscle is good for hormones, it's good for not breaking bones when you get older. Um, balance is important. And then the other one is aerobic. VO2 max, we know VO2 max is correlated with very long life. Um, and so you do need to lose your breath minimum three times a week, ten minutes. Um, it's rare that people talk about sex as a, a way to exercise. I see your eyes bulging. Um-

    3. CWChris Williamson45:11

       I'm just waiting to see where you're gonna go.

    4. DSDr. David Sinclair45:13

       [chuckles] Well, I, I was looking at, at, at a, at a tweet the other day, uh, at an X, whatever we call them now, and it was saying... Oh, y- I think... I won't say who, who it was, but they said, "Oh, you can lose your breath 10 times, uh, for 10 minutes, three times a week by doing XYZ." And I thought, "Well, no one ever mentioned sex." So if you have an active sex life, count that as part of your daily longevity routine or your weekly longevity routine.

    5. CWChris Williamson45:39

       Okay.

    6. DSDr. David Sinclair45:40

       But also-

    7. CWChris Williamson45:40

       Sufficiently vigorous sex can be-

    8. DSDr. David Sinclair45:43

       If you can go for 10 minutes vigorously, that's a good start for longevity.

    9. CWChris Williamson45:48

       Uh-huh. There's sometimes restrictors for that, um, that aren't simply cardiovascular, but go on.

    10. DSDr. David Sinclair45:53

        [laughs] Well, you can supplement it with, um, you know, just running on a treadmill, going outside, rowing, sport, all of this stuff. Just as long as... The, the way to know if you're exercising enough to build up your VO2 max is you shouldn't be able to carry out a conversation easily like this.

    11. CWChris Williamson46:08

        Mm-hmm.

    12. DSDr. David Sinclair46:08

        You're panting. Um, that's my judge. I need to do a lot more of it. I-- These days I tend to do a lot of my exercise aerobically running to catch a plane. Um, I admit that I'm not the perfect role model for exercise. Um, but I do know what the science says, and that is the combination of the, the weights, the balance, uh, and the aerobics.

    13. CWChris Williamson46:29

        Uh-huh. What about zone two? You haven't mentioned low and slow.

    14. DSDr. David Sinclair46:34

        [sighs] Well, if you can't do fast and quick and hit, uh, low and slow is fine. Walk, move, get up. Uh, I'm, I'm always walking around my office. I have a standing desk. I rarely sit down. So that kind of exercise is very good, certainly for balance, um, overall metabolism. So yeah, I, I try not to sit at all. Um, I'm sitting now, but I rarely sit during the day. Um, it's one of the things people find weird about me. They come to my office and I'm, I'm, I'm pacing, I'm twitching. I'm, I'm often chewing gum.

    15. CWChris Williamson47:06

        That's not the same as zone two though, right?

    16. DSDr. David Sinclair47:08

        No, no. Need to do a little bit more than that. Um, what I like to do as a sport, um, you know, tennis could get you there. I do a lot of gardening, so I'm carrying stuff.

    17. CWChris Williamson47:19

        Gardening is a sport?

    18. DSDr. David Sinclair47:21

        Yeah. That's my sport actually.

    19. CWChris Williamson47:22

        Okay.

    20. DSDr. David Sinclair47:22

        It's my big hobby.

    21. CWChris Williamson47:23

        Interesting.

    22. DSDr. David Sinclair47:24

        Lifting a lot of heavy plants and building walls and hammering and drilling and-

    23. CWChris Williamson47:29

        Mm-hmm

    24. DSDr. David Sinclair47:29

        ... all of that stuff. Um, but yeah, a little bit... You know, k- kayaking is something that I like is good. I'm not out of breath, but I'm out... You know, I'm getting a good workout.

14. 47:39 – 50:43

    Why Quality Sleep Is Essential for Longevity

    1. CWChris Williamson47:39

       Sleep and recovery and rest. What-

    2. DSDr. David Sinclair47:42

       Yeah

    3. CWChris Williamson47:43

       ... what is the most up-to-date data saying around that from a longevity?

    4. DSDr. David Sinclair47:47

       It's still the same. Um, it's... You do need to watch your sleep. If you're not getting quality sleep or sleeping for that long, it's gonna affect your metabolism. Figure out how much sleep your body needs at a minimum. You can do that using some of these rings. It's very good for that. Some people need eight hours, some people need seven hours. Typically, if you're younger, you need more. The good thing about getting older is you need less typically. But it's also about quality. Um, I can get away with five hours sleep, and my HRV is still in the 80s, 90s, um, because I'm getting deep sleep. I'm not drinking caffeine late in the afternoon. Um, I practice as best I can relaxation, meditation, practices breathing.

    5. CWChris Williamson48:27

       Mm-hmm.

    6. DSDr. David Sinclair48:27

       And that gets me to sleep and into REM and deep sleep pretty quickly. I also take a supplement that, uh, my partner Serena makes, and, um, it's got L-theanine and some other stuff that also I know from my own experiments gets me into deep sleep quickly. And so my efficiency is typically, according to these rings, uh, in the 90s, 90%, sometimes close to 100. And then I can get away with less, um, which is nice 'cause I travel a lot.

    7. CWChris Williamson48:55

       I think that's the big learning that everybody who starts using a wearable takes away from it, which is you're sleeping way less than you think you are. Like, well, you know, I was in bed for eight hours. It's like, no, you thought that you went to bed at 11:00, but it was actually sort of 11:30, and you were reading or watching TV until nearly 12:00. And then your actual efficiency was maybe 85%, so that seven hours has turned into 5:45 or 6:00 or something.

    8. DSDr. David Sinclair49:21

       Mm-hmm.

    9. CWChris Williamson49:21

       And yeah, it's stark. I've got maybe 1,500, maybe 2,000 nights on Whoop tracked, right, over the years, and it, it's-- you're just always sleeping less than you think you are. Like, if you don't have money to buy a wearable, just the rule is you're sleeping less than you think you are. That's it.

    10. DSDr. David Sinclair49:39

        Yeah, I agree, and especially if you're, you're eating late, drinking coffee or tea late, uh, or matcha. Caffeine a-and alcohol are big ones for bad sleep-

    11. CWChris Williamson49:49

        Mm

    12. DSDr. David Sinclair49:50

        ... um, not just stress. Having a hot room or too many blankets is another mistake that a lot of people make. Um, you can get those beds that cool you off.

    13. CWChris Williamson49:59

        Eight Sleep. Eight Sleep is-

    14. DSDr. David Sinclair50:00

        Eight Sleep.

    15. CWChris Williamson50:00

        Anyone that's not using an Eight Sleep, it's medieval. I understand they're expensive, but there's no one that I've got to do-- Yeah, they're a partner on the show or whatever, but, like, this has got nothing to do with it. Every single person that I've got to try it can't believe that what life was like before they had a, a cooled... And there's other cheaper versions out there, I'm sure. Eight Sleep's the best, but there's, there's, there's other ones that you can get. Trying to cool your bed from outside of your bed when the job of your bed is to keep the temperature in the bed the same is kind of a little bit like fighting against the tide.

    16. DSDr. David Sinclair50:31

        Yeah. Oh, exactly, and you should wake up every morning feeling totally rested, excited about the day.

    17. CWChris Williamson50:36

        Mm-hmm.

    18. DSDr. David Sinclair50:37

        If you're waking up and like, "Oh, I need a coffee. Ugh, I need a shower," you're probably not getting the sleep that you need.

15. 50:43 – 54:42

    Can Overthinking Shorten Your Lifespan?

    1. CWChris Williamson50:43

       Mm. You mentioned stress as well as kind of the fourth pillar when it comes to lifestyle.

    2. DSDr. David Sinclair50:48

       Mm.

    3. CWChris Williamson50:48

       What does that look like? How do you, how do you come to think about stress as a longevity doctor?

    4. DSDr. David Sinclair50:52

       Yeah, well, you can measure cortisol, for example, um, or DHEA cortisol r-levels. We're all stressed. You know, the, the old days of sitting around a campfire are not really there anymore. We're driving to work. We're worried about income, and so what we want to do is, uh, learn to, to deal with the daily stress. You know, the world is changing faster than ever. So what, what I've learnt personally is really not to let worries of life get me down. Um, I try not to focus on them. I have a happy place, which is an orchard, uh, on Cape Cod, and my mind, when it's stressing out and I feel my body tense up, I take myself there. I breathe. I'm amongst the trees. Um, if it gets really bad, I, I go there [chuckles] physically and do some work. But yeah, it's, it's all about learning not to ruminate. Um, and a lot of us A types, I'm sure you in your success are like that, "What did I r-do wrong? I could do that better. I'm worried about tomorrow. I'm worried about next week. I'm worried about ten years." Um, don't do that. It took me f-50 years of my life to figure out don't do that and how not to do that, and the last-

    5. CWChris Williamson52:06

       How do you, how do you stop worrying?

    6. DSDr. David Sinclair52:08

       You have to train yourself. It's like, don't be an idiot. Stop thinking about it. Um, it's not gonna kill you if you distract yourself with something else. Overthinking something is, is a real, uh, uh, issue for modern life, and, uh, so I don't do that anymore. If I, uh, find myself overthinking, I'll just say, "I'll think about it later," put it off to the side. And I used to be the kind of guy that I had to text back immediately and email back immediately. Put it aside. I'll get to it.

    7. CWChris Williamson52:36

       I think a lot of people are riven by the overthinking intrusions, that they just can't get their brain to focus on what's in front of them. There's always this concern. There's always this situation that could be a little bit worse, this thing that could make life a little bit harder that's coming down next, and yeah, you're, you're, uh, kind of being puppeted by these ghosts of the future that haven't yet come about.

    8. DSDr. David Sinclair53:02

       Yeah, that's the thing. What you realize when you get to my age, I'm now 57, is that it's never as bad as you think, and what, what I do know is I depend on myself. I know that these big problems in my life, and I've had big ones, deaths and issues, um, you get through it. You trust yourself. You know. You know, maybe when you're a teenager, in your, your 20s, you don't know that you can get through these things. I'm at an age where I know I'm not gonna die. I'm gonna get through it. It's gonna be okay. Um, if I have a problem, I'll solve it. Um, the sooner you can realize that, that you are capable of anything if you put your mind to it-

    9. CWChris Williamson53:41

       Hmm

    10. DSDr. David Sinclair53:41

        ... then you shouldn't stress about problems that come up.

    11. CWChris Williamson53:44

        Tell me if this sounds familiar. You train regularly. You eat reasonably well. You feel fine, but you're just kind of going off vibes. Most people have absolutely no idea what's going on inside their body, and that is why I partnered with Function. Function gives you access to more than 160 advanced lab tests spanning hormones, heart health, kidney function, and even detects early signals linked to more than 50 types of cancer. To put that in perspective, your typical annual physical might test 20 markers. Function runs over 160. It's huge. Best of all, you test twice a year, and everything lives inside of a simple dashboard. So you track trends over time, make sure you're moving in the right direction, and this level of testing would usually cost thousands, but with Function, it is $365 per year, just $1 a day to actually know what's happening inside of your body. And right now, you can get $25 off, bringing it down to 340 bucks. Get the exact same blood panels that I use and save $25 by going to the link in the description below or heading to functionhealth.com/modernwisdom. That's functionhealth.com/modernwisdom.

16. 54:42 – 56:24

    What Longevity Drugs Does David Take Every Day?

    1. CWChris Williamson54:42

       Okay, let's talk about your current drugs stack. What are you taking? How's your daily stack changed versus what you were doing when you wrote the book?

    2. DSDr. David Sinclair54:51

       It hasn't changed. That's the amazing thing. Uh, I thought I'd have to change things depending on the science, but the science has held up. Uh, so in the morning, and if you go to page, uh, what is it? 304 of Lifespan, it's still in, still there, uh, and I still do that, uh, resveratrol. It's been back and forth controversial. It's not controversial in scientific circles. There's a few naysayers, but they make a living out of it. Uh, resveratrol is from plants that are stressed, and they activate Sirtuin, this resetter of and slower of the epigenome, uh, noise. So I've been taking about a teaspoon, call it a gram of resveratrol every morning, uh, almost every morning for the last, gee, probably 20 years. Doing all right. Um, it seems to help in clinical trials. It's been tested in a number of clinical trials. I mix it with e-either a little bit of olive oil, that's my calories, um, or, uh, Greek yogurt or vegan yogurt, and, uh, it's been good to me. Um, I also take that with, uh, NMN, which is an NAD supplement. It's a precursor. We studied both in my lab. And, uh, we just resubmitted a paper. This is something I can reveal. We just resubmitted a paper, uh, to be published that showed that NMN is very good for the health of old mice and can extend the lifespan of mice, particularly females. And, uh, so that'll come out probably-

    3. CWChris Williamson56:15

       Resubmitted?

    4. DSDr. David Sinclair56:17

       Yeah. We, we had reviewers' comments, criticism, spent another year working on it to please them and send it back. We'll see what

17. 56:24 – 1:13:21

    The Truth Behind Controversial Longevity Drugs

    1. DSDr. David Sinclair56:24

       they say.

    2. CWChris Williamson56:24

       Hmm. What, what was the controversy? 'Cause I know since the last time we spoke, there's been some furor around resveratrol, some more furor around N-N-NAD, maybe NMN as well.

    3. DSDr. David Sinclair56:36

       Yeah.

    4. CWChris Williamson56:36

       Can you explain what happened?

    5. DSDr. David Sinclair56:37

       Yeah, sure. Uh, these are all typhoons in a teacup or whatever it is. I can't stop drinking your drinks. Very good.

    6. CWChris Williamson56:45

       Good.

    7. DSDr. David Sinclair56:46

       Um-

    8. CWChris Williamson56:46

       That's all I needed.

    9. DSDr. David Sinclair56:47

       The, uh ... So let's start with resveratrol. I try not to bore everybody. Um, Sirtuin is an enzyme. I'll use my hands. It's an enzyme that carries out reactions that stabilizes the epigenome so it doesn't decay. So think of it as stopping the corruption of the software. More Sirtuin is better. So there are two ways to activate Sirtuin, um, with, with a pill rather than exercise and dieting. Um, and if you do all of them, I think it's the best. So you can either take resveratrol, and that we showed in 2003, long time ago, I'm old, uh, activates Sirtuin directly. So the enzyme is removing chemicals from the epigenome and making it stable, and it can do it slowly. You know what a Pac-Man is? You're old enough. Uh, so it's chewing away, uh, the chemicals, stabilizing things. Faster, the better. Resveratrol, you know, binds physically to the enzyme and now makes it chomp faster, okay? The controversy that came up was that Pfizer, a team at Pfizer, not the whole company, just a group in the company, put out a paper in 2010 that said resveratrol doesn't do this. It, it must be an artifact. It's doing something else that makes it look like this. Um, so we, we then spent three years testing that and found exactly how it works to the atomic level. We could even block it by changing an amino acid in this protein. And we actually have a study now that we've made a mouse that has this block, and resveratrol doesn't make the mouse healthier anymore. It doesn't live longer. So that's as good as evidence that you could get that we were right in the first place and Pfizer was wrong. Um, and we've put out papers since, and others have shown that we were right. So no controversy there.

    10. CWChris Williamson58:32

        Well, going head-to-head with Pfizer is no small task.

    11. DSDr. David Sinclair58:34

        It was brutal. Uh, that was one of the hardest things in my life because I remember try to def-- trying to defend myself in public.

    12. CWChris Williamson58:41

        Hmm.

    13. DSDr. David Sinclair58:42

        It was on NBC. And I said, "I'm not sure what Pfizer is doing, but our chemicals don't kill mice, and they activate the enzyme." And the comments were brutal. "Sinclair thinks he's better than Pfizer. Pfizer knows what they're doing." Um, I will say that I don't have ill will towards those scientists because it's a, the job of scientists to challenge theories. Um, what I do have a problem with is the, the people who still say it's wrong and are trying, you know, just to get at me. They're-

    14. CWChris Williamson59:14

        What's the remnant? If you've put something out which pushes back against Pfizer, what is the remnant argument?

    15. DSDr. David Sinclair59:21

        There isn't one. The, the problem is that the, the m- what I've gotten to see in my career over 30 years is the media loves the negative story, but the redemption story isn't as popular. So it's never come out in these journals like Nature. They put out the negative story, but they never did the, "Oh, we were... That was wrong." So it's just a matter of reporting. Um, but in scientific circles, everyone's read our science paper, uh, from 2013, and it's not debatable.

    16. CWChris Williamson59:52

        That's put it to re- the, the evidence is put to rest, in your opinion?

    17. DSDr. David Sinclair59:56

        Yeah.

    18. CWChris Williamson59:56

        Yeah.

    19. DSDr. David Sinclair59:56

        Yeah. It's at the atomic level. Unless you want to complain about atomic theory, you know, we're, we're done here.

    20. CWChris Williamson1:00:02

        Okay. And what happened with NAD, NMN?

    21. DSDr. David Sinclair1:00:06

        Uh, so yeah, the... Let's bring everyone up to speed on what NAD is. So Sirtuin also can be activated by giving it fuel, which is NAD. Sirtuin chomps with NAD. Um, and in fact, this is not often known, the chemical that it takes off the epigenome structures is donated to NAD. So without NAD, you can't take the chemicals off. And more levels of NAD make it work faster and better, and if you give it to cells, uh, you see more stable and healthier cells. Um, there was dogma that NAD levels went down with aging and that boosting it back up was healthy. So the second part is true. We have shown in cells, in animals, and even in humans for the last, and by we, I mean the field, not just my lab, that raising NAD levels above normal baseline is very good for humans. Okay? I can give you examples. Um, Shelly Bason, you could look up, uh, in PubMed. He's got a couple of really good papers giving, uh, NMN, which is the precursor to NAD, to people that are either obese, uh, or have diabet- prediabetes or even super fit ones. Um, maybe the super fit isn't published yet, but he's done the work and reported about it. Um, you see improvements from lipids, whole bunch of lipids, uh, cholesterol, blood pressure, body weight. So raising NAD, I think most people would, would say that it's good for, for humans and animals. Okay? And again, we're going to publish that it's good for longevity too. Where the debate that came up, I think you're talking about the one that was maybe a few months ago. Um, somebody showed that human blood levels in white blood cells, the white blood cells don't have less NAD as you get older. So some people who love to make a living of being naysayers, especially towards my career, uh, jumped on that and said, "The whole theory is wrong. If white blood cell NAD levels don't go down with aging, then the whole theory must be incorrect."

    22. CWChris Williamson1:02:05

        Hmm.

    23. DSDr. David Sinclair1:02:06

        Which is, as you can tell, is complete BS. In fact, we, we've known for probably a decade that that was true, and it, it doesn't affect the theory. We know that raising NAD levels in humans, either by exercise, uh, or by supplementation, is good for you. So it was crazy to say the whole theory fell apart. It was just a way to get clicks, I think.

    24. CWChris Williamson1:02:26

        Hmm. What's the status? I'd looked at something to do with it was a pharmaceutical, then it was a supplement, and now I don't know what the level of access is with NAD and stuff at the moment. How... What's... How is that classified?

    25. DSDr. David Sinclair1:02:39

        Yeah. Um, or just a final thought. There is a really good study that showed that people who have lower levels of NAD in their muscle, um, I think it was are not as metabolically active as those that have higher levels-

    26. CWChris Williamson1:02:52

        Hmm

    27. DSDr. David Sinclair1:02:52

        ... and... or they had metabolic syndrome. Anyway, we could check it out, but, but there is some good correlations between NAD levels and, and age-related conditions. Want to be accurate. All right, so the FDA thing. Um, basically it was that there's a rule in the US that if any molecule, whether it's natural or synthetic, goes into a human clinical trial before it's on the market, people can't put it on the market, 'cause then it negates the reason to do a clinical trial, and we need clinical trials to know if things work. Makes sense. The law makes sense. Where things got crazy was, uh, a company that I started called MetroBiotech started a clinical trial with NMN, and a little later, people started putting NMN on the market. And I've always said publicly, you can read it, "Fine, let's do both. Let's do the clinical trials, make a drug. It's gonna be pure, it's gonna be tested, and there'll be supplements that are less rigorously produced for people that are not sick. But for the sick ones who have diabetes or need a drug, we'll have that." Happy world. Um, the legal team at MetroBiotech made a decision without my approval, actually with my disapproval, to, um, write a letter to the FDA pointing out that it, it, that there was this law that they shouldn't have simultaneously sales and clinical trials. Uh, I objected. Um, the FDA, uh, initially said, "You shouldn't be selling, uh, NMN on the market in the US according to that law," though they didn't enforce it, and then it was recently reversed.

    28. CWChris Williamson1:04:36

        So now it is enforced?

    29. DSDr. David Sinclair1:04:38

        It... No, I mean the opposite. The FDA s- I believe says it's okay to have NMN on sale now.

    30. CWChris Williamson1:04:44

        Oh, interesting. Okay.
18. 1:13:21 – 1:17:16

    Can Erectile Dysfunction Medication Treat Cancer?

    1. CWChris Williamson1:13:21

       What's all this hype around erectile dysfunction medication?

    2. DSDr. David Sinclair1:13:25

       [laughs] That's a lead in question. Um, well, yes, it's recently come into social media because it was found that, that, that, uh, these ED drugs are also good for some types of cancer and can change the immune system so that it goes from protecting the cancer to killing it. Uh, and I tweeted out, "What's not to love?" And it... millions of people saw that. Um, but I'm serious. I, I take, uh, uh, what is it? Um, Cialis is the common name, um, tadalafil, um, every morning. A s- a low dose. It's just, uh, a, a little bit. And I, I do that because In 2012, we published a paper that showed that one of the, the most pernicious causes of aging is low blood flow, and that we could reverse that with NMN through Sirt1, more blood flow. And it's really underappreciated how much a lack of blood flow leads to diseases, your... Especially your, your muscles and your brain. And so I take this low dose in the hopes and expectation that I will, if I get dementia, it will be a decade later.

    3. CWChris Williamson1:14:39

       Mm.

    4. DSDr. David Sinclair1:14:39

       And now add on that cancer killing, it's an amazing drug. And it was actually not even developed initially for these. It was-

    5. CWChris Williamson1:14:46

       It was an angina medication, wasn't it?

    6. DSDr. David Sinclair1:14:48

       Exactly. Right?

    7. CWChris Williamson1:14:48

       Do you know the story of why they realized it had that side effect?

    8. DSDr. David Sinclair1:14:53

       Um, was it, was it pulmonary-

    9. CWChris Williamson1:14:56

       They-

    10. DSDr. David Sinclair1:14:56

        ... uh, hypertension? I think the-

    11. CWChris Williamson1:14:57

        When, when they were doing the, the trial, typically you do a, a, a meds trial and patients come back into the lab and you ask them to give the drugs back and nobody has an issue. But none of the guys wanted to give the drugs back anymore.

    12. DSDr. David Sinclair1:15:09

        [laughs]

    13. CWChris Williamson1:15:09

        And the nurses noticed-

    14. DSDr. David Sinclair1:15:11

        Mm

    15. CWChris Williamson1:15:11

        ... that the, uh, patients, when they were doing their interviews, were sitting cross-legged.

    16. DSDr. David Sinclair1:15:16

        [laughs]

    17. CWChris Williamson1:15:16

        And they had this strange-

    18. DSDr. David Sinclair1:15:19

        Yeah

    19. CWChris Williamson1:15:19

        ... the contorting of the posture to try and hide the fact that they all had hard-ons.

    20. DSDr. David Sinclair1:15:23

        Yeah.

    21. CWChris Williamson1:15:23

        And, uh, it- they said, "Hey, we, we... The angina thing we're not so sure about, but we've done some wonderful stuff to the penis." Uh-

    22. DSDr. David Sinclair1:15:30

        Yeah. Well, I, I can say taking a low dose... The good news is it doesn't make your, your penis get erect without warning.

    23. CWChris Williamson1:15:37

        Okay.

    24. DSDr. David Sinclair1:15:37

        That isn't a problem.

    25. CWChris Williamson1:15:38

        Yep.

    26. DSDr. David Sinclair1:15:39

        But the low dose really, um, I've... Let's put it this way, I haven't had any downsides yet.

    27. CWChris Williamson1:15:43

        Fantastic. Uh-

    28. DSDr. David Sinclair1:15:44

        There's, there's one other thing, Chris, I want to say which, before I forget in my old age and my lack of blood flow, is, um, so there's a, there's a study in mice at least that hints that lack of blood flow to hair follicles is a reason that you lose hair. And so my hope scientifically is that, uh, continuing to get blood flow in my hair follicles will keep my hair.

    29. CWChris Williamson1:16:06

        More hard-ons, less balding. That's the equation.

    30. DSDr. David Sinclair1:16:09

        Yeah.
19. 1:17:16 – 1:21:15

    The Hidden Danger of Heavy Metals in Supplements

    1. CWChris Williamson1:17:16

       Yeah. Um, what about omega-3s? You know, omega-3s commonly touted as something that's very important for people's longevity. Where do you come in to land on omega-3 levels and supplementation?

    2. DSDr. David Sinclair1:17:28

       Uh, I take an omega-3. Um, the, the data looks really pretty good that, uh, if you have some of that, it's anti-inflammatory. Whether or not it totally prevents heart disease, it, it's controversial now, but-

    3. CWChris Williamson1:17:41

       Have you got a brand that you prefer?

    4. DSDr. David Sinclair1:17:45

       Yeah, but I won't say it. Um-

    5. CWChris Williamson1:17:47

       Okay. I'll tell you what I use. Nordic Naturals two X are the best.

    6. DSDr. David Sinclair1:17:50

       Um, I do like, I do like them.

    7. CWChris Williamson1:17:53

       Yep.

    8. DSDr. David Sinclair1:17:53

       Um, their products are really pure and distilled, so you want to avoid the cadmium and lead products.

    9. CWChris Williamson1:17:59

       The what, what?

    10. DSDr. David Sinclair1:18:00

        The ones that have heavy metals.

    11. CWChris Williamson1:18:01

        Okay. So I, I, I mean, I remember this. My mom would tell me this 25 years ago when I was a kid, and she would be taking... And there would always be this line of low-quality cod liver oil back in the day. Low-quality omega-3 supplements aren't really that good for you. So this is like, you know, mythological-

    12. DSDr. David Sinclair1:18:22

        Yeah

    13. CWChris Williamson1:18:22

        ... fucking ancient wisdom.

    14. DSDr. David Sinclair1:18:24

        It, it really is. And actually, while we're on the topic of, um, contamination, I, uh, and other labs have measured, uh, supplements and they're often contaminated with things. And I even got sucked into a lawsuit because I said I tested this product and it... Or this type of product, and it had contamination. But I, I do want to say, at the risk of some litigious activity against me, that NMN and these NAD precursors can have contaminants in them.

    15. CWChris Williamson1:18:56

        Hmm.

    16. DSDr. David Sinclair1:18:56

        Now, I don't sell, I don't market anything. I don't get any money despite people using my name and even video across the internet. So I have nothing to gain or lo- really lose by this. Well, I've got a lot to lose, but nothing to gain. NMN can have things like... Well, first of all, I think the study that was published, it's worth looking at by Andrea Meyer, um, she's out of Singapore. She found that a lot of the NMN supplements didn't have NMN in it, and if they did, it was a low amount. And we found in my lab, which I don't think is in Andrea's paper, is that there is endotoxin in NMN bulk end supplements. Endotoxin comes from bacteria. It causes inflammation. It's part of the purification process, but they don't get rid of it. And we found out the hard way. We were feeding it to mice to make them live longer, which is not gonna work if it's contaminated.

    17. CWChris Williamson1:19:44

        Hang on. So even the NMN that you were using in your lab that you thought was pure was so contaminated that it was infecting the study participants?

    18. DSDr. David Sinclair1:19:54

        Right. 100%.

    19. CWChris Williamson1:19:54

        Wow.

    20. DSDr. David Sinclair1:19:55

        So we've had to really work hard with manufacturers to get it really pure.

    21. CWChris Williamson1:20:00

        How hard do people need to work? If they... If somebody's taking an NMN supplement now, is there anywhere that a normal person can go that's not gonna risk being contaminated?

    22. DSDr. David Sinclair1:20:09

        Mm. Well- If I ever mention a brand, it's gonna be... It'll blow up the internet. Might, might bring it down. But, um, I will say that to help the viewers, um, the, and the listeners of this show, I would go for a company that has a strong reputation that provides the analytics. So sometimes they give the sh- spec sheet, and you can see the purity. And, um, you know, some companies, they've got such a big reputation, they're not gonna risk adulterating it or putting something else in it or giving you less. Um, GMP is important always. Any supplement should be, uh, good manufacturing practices, um, USB label. Look for those badges of purity. Um, and if your company that you like doesn't share the analytics online, you can write to them and say, "Can you please share that batch?" And they often do that.

    23. CWChris Williamson1:21:02

        'Cause it's not cheap, right? They're not cheap interventions for people, and if you're spending a lot of money on something, you wanna make sure that it's actually... Uh, the worst thing is I'm taking this thing that I think is gonna make me more healthy, and it's actually making me sick.

    24. DSDr. David Sinclair1:21:13

        That's the real problem. Um, and so what,

20. 1:21:15 – 1:24:24

    The Benefits of Creating a Longevity Community

    1. DSDr. David Sinclair1:21:15

       um... And I'm gonna do a shameless plug, if that's okay. Um, I'm launching a community, uh, a website community for us to figure this stuff out together. I'll be testing products. We'll learn what works together. Um, and I hope that it becomes the world's largest longevity community.

    2. CWChris Williamson1:21:33

       What does the... What, what's the community built around? What is it?

    3. DSDr. David Sinclair1:21:36

       Yeah, it's called lifespan.com. So my show is Lifespan. This is the website version. Um, my goal ultimately is to fix healthcare across the planet. We've done a top-down government, big industry HMO. Um, we know that doesn't work. The US especially is spending close to 20% of GDP on the healthcare and got some of the worst healthcare. So we've gotta do something. So grassroots movement, lifespan.com will be a community that comes together to learn what works, what doesn't. Um, and eventually where I wanna take this is that we, we change how healthcare is done, and with AI, with knowledge, with, you know... We're also funding medical research and testing of brands, so we know what's pure, and we'll find new medicines together. I wanna share in the profits of that with all of the members. So that's being launched soon. Um-

    4. CWChris Williamson1:22:30

       That's cool

    5. DSDr. David Sinclair1:22:30

       ... it, it's probably launched by now. Um, there's, for members... So there, there's an unpaid version. You can do show notes, and you can see some, uh, some stuff. But if you, um, pay the $8 a month, um, we've pulled together something really interesting. We've got this community that we've built, but also there's information w- that will basically complement what we've been talking about today. There's a magazine, world's first magazine written, well-written by people who are doing the research. So you don't have to rely on some, uh, newspaper or reporter who doesn't know anything, who also wants clickbait. Um, I actually brought a copy of this magazine. I had it printed in hard copy just for you.

    6. CWChris Williamson1:23:12

       Oh, let's get it. I wanna see.

    7. DSDr. David Sinclair1:23:14

       You haven't seen it. This is, this has been hidden here. This is Lifespan Magazine, first one I've given out to anyone. And this is a gorgeous magazine that every member gets online.

    8. CWChris Williamson1:23:27

       What if aging isn't damage but lost information? A radical idea now entering human trials.

    9. DSDr. David Sinclair1:23:33

       Oh, that's, that's the paper from Nature that I thought I'd give you as well in 2020 that changed everything.

    10. CWChris Williamson1:23:38

        This is so cool. Thank you.

    11. DSDr. David Sinclair1:23:40

        Have a look inside. I'm so proud of how it looks now. Um, this is going to be coming out every month, and it's got about 100 pages of the real science, the real stories of what it's like and what we're learning before it even comes out in journals and in the media.

    12. CWChris Williamson1:23:58

        Oh, this is cool.

    13. DSDr. David Sinclair1:23:59

        Inside this look.

    14. CWChris Williamson1:23:59

        I mean, it's very beautifully put together. Beyond Your Birthday: Steve Horvath on the Science of Epigenetic Aging. I know Steve Horvath.

    15. DSDr. David Sinclair1:24:06

        Yeah. Yeah, Steve discovered the epigenetic clock.

    16. CWChris Williamson1:24:08

        Can a simpy mul- simple multivitamin mineral supplement slow down aging? This is awesome. Congratulations.

    17. DSDr. David Sinclair1:24:15

        Thank you.

    18. CWChris Williamson1:24:16

        Congratulations.

    19. DSDr. David Sinclair1:24:16

        I'm very proud of the team. It's a, it's a small but mighty team that we really- we're really driven by mission. We wanna change the world, and we want everyone to join us in

21. 1:24:24 – 1:31:04

    Sauna vs Cold Plunges: Which Is Better for Longevity?

    1. DSDr. David Sinclair1:24:24

       it.

    2. CWChris Williamson1:24:24

       Unreal. Uh, okay, other interventions, other stuff that's happened, 'cause since we, since we first sat down, the world of longevity, biohacking has really sort of... It's not exploded. I think it's, I think it's become more sophisticated. You may say otherwise. The evidence may say otherwise.

    3. DSDr. David Sinclair1:24:41

       Mm-hmm.

    4. CWChris Williamson1:24:42

       But at least from the, like, self-experimentation, uh, you know, 2017, '18, '19, it was a lot of The Biohacker's Handbook. It was, you know, Ben Greenfield's, a friend of the show, he, s- sticking ultrasound things on his penis to see if he can improve his-

    5. DSDr. David Sinclair1:25:01

       [laughs] Yeah

    6. CWChris Williamson1:25:01

       ... his erection quality and his orgasm length and stuff. And then it seems like it's really come on data-backed, a lot more, um-

    7. DSDr. David Sinclair1:25:09

       Hmm

    8. CWChris Williamson1:25:10

       ... evidence-based crowd stepping into this.

    9. DSDr. David Sinclair1:25:13

       Well, thank you to, to you, for example. Uh, guys like you are bringing scientists like me and people who know what they're talking about, so the people can hear it-

    10. CWChris Williamson1:25:22

        Mm-hmm

    11. DSDr. David Sinclair1:25:22

        ... from the horse's mouth. Whereas before, it was just somebody hyping and selling stuff which you couldn't trust.

    12. CWChris Williamson1:25:28

        It's true. I mean, what's been interesting has been to see, at least in, in Greenfield's case, like, how right he was about tons-

    13. DSDr. David Sinclair1:25:35

        Yeah

    14. CWChris Williamson1:25:35

        ... of stuff super early on.

    15. DSDr. David Sinclair1:25:36

        Yeah, though I didn't mean to imply Ben-

    16. CWChris Williamson1:25:38

        No, it-

    17. DSDr. David Sinclair1:25:38

        ... was one of those people.

    18. CWChris Williamson1:25:39

        But there's so many pe-... Even, uh, uh, uh, Timo, Timo Areena was it that wrote The Biohacker's Handbook? It's his coffee table book I've still got in my house in Newcastle. And I look at some of that, and it's the same as the bodybuilder thing. So many bodybuilders stumbled onto a particular way to look at health or dieting or whatever that a decade later, science then comes back around and says, "Oh, yeah, that's the way." But then also there are a lot of people that throw shit at the wall, and much of it doesn't stick.

    19. DSDr. David Sinclair1:26:07

        Yeah.

    20. CWChris Williamson1:26:07

        One of the most, uh, popular interventions that people are talking about, contrast therapy, sauna and ice baths. What does the evidence say around cold and heat exposure for longevity?

    21. DSDr. David Sinclair1:26:21

        Increasingly, we're learning. Um, in 2019 when you and I first met, there was very little evidence actually. Um, and you're right, biohacking was something that was looked down upon, especially by doctors, um, and the public didn't know what was going on. Uh, then came the pandemic, and most people saw the mortality and it's like, "What are we gonna do?" And it's amazing to see what's happened since, that it's become mainstream and even doctors have had to learn about this because p- their patients are coming to them-

    22. CWChris Williamson1:26:50

        Mm

    23. DSDr. David Sinclair1:26:50

        ... with more knowledge than they have, especially with AI now. Um, but we are, we are in a world now where the individual can know more about a certain topic than their own physician, which is incredible. Um, that does include sauna and cold baths. When we met 2019, there was a little bit of data in saunas and nothing on cold baths except a mouse bunked in the cold. Um, now there's much better evidence. Um, I put it in my book, Lifespan, because, uh, I was told by the editor that that would be interesting, but I was hesitant because there was such little data on saunas and, and nothing on ice baths really. That's different now. I can now say as a scientist, Scouts Honor, I, I was a Scout, I forget how we do it, um, that definitely sauna, there's a lot of evidence. Mostly, uh, Nordic men have been studied, uh, less women. But if you do regular, what they call sauna bathing in Finland a few times a week, your rate of heart disease can be much less and-

    24. CWChris Williamson1:27:50

        Mm.

    25. DSDr. David Sinclair1:27:51

        And that is reproducible. So that, I think saunas are great. Um, I try to do some of that myself, um, as hot as I can bear. Ice baths contrast, it makes sense scientifically, hasn't really been studied, but, uh, cold therapy, we do know it can activate brown fat, which is very good.

    26. CWChris Williamson1:28:11

        What does that mean?

    27. DSDr. David Sinclair1:28:12

        Well, so we, we actually, going back in history 30 years ago, we didn't know that we adults, humans had, uh, brown fat. Babies have brown fat. It's a highly metabolically active type of fat in babies that keeps them warm 'cause they can't shiver initially. Um, and then using PET scanning, people at Harvard, some friends of mine discovered that adults can have brown fat on their own bodies as adults. Um, often in, they're in the back. You can get it, more brown fat by, by doing cold bath- cold plunges and being cold. Um, and-

    28. CWChris Williamson1:28:48

        Do you want more brown fat?

    29. DSDr. David Sinclair1:28:50

        Yes. So I was gonna say the, the brown fat's full of mitochondria, which are healthy. They s- Brown fat seems to secrete factors that are good for health. Um, but yes, people that have more brown fat tend to have better metabolism in general, and they also burn more energy, which is good in today's world where there's, well, too much food around. So yeah, in general, yes, brown fat is considered very healthy. Um, but the older you get, the harder it is to, to make and convert from white to brown or beige.

    30. CWChris Williamson1:29:21

        Mm.
22. 1:31:04 – 1:35:09

    Is Bryan Johnson’s Protocol Actually Working?

    1. CWChris Williamson1:31:04

       What do you make of Bryan Johnson's approach to longevity?

    2. DSDr. David Sinclair1:31:07

       Well, it's totally different. Um, it- Putting the two of us side by side, some people do, it's, it's not the same animal. Uh, I'm doing science, I'm doing the research, I'm figuring out the molecular mechanisms. Um, he's a complement to that. He is self-experimenting. It's not a clinical trial, obviously. He will admit that. But where I think Bryan shines, um, is in a couple of areas. He's very courageous. I like that he stuck his neck out. I, I have a lot of, uh, admiration for those people who are brave that way. Um, he's also been, um, helpful bringing a spotlight to the field of longevity, and I remember a lot of my colleagues, uh, my highbrow colleagues in longevity really said he's the worst thing that's, that's happened to our f- to this field. He brings a bad name to longevity. But I, I disagree. I think that he, that we as a field of scientists had a marketing problem. As much as we talked about longevity, it wasn't getting through.

    3. CWChris Williamson1:32:07

       Mm.

    4. DSDr. David Sinclair1:32:08

       Up until 2020, almost nobody had used this word even. Bryan came along, um, I came along, but definitely Bryan got a lot of attention, and I think it's been helpful to wake people up from They're stupor

    5. CWChris Williamson1:32:22

       Mm-hmm

    6. DSDr. David Sinclair1:32:23

       Uh, not everybody, but a lot of people just live their lives and eat whatever they want, um, do a little bit of exercise. Bryan said, "We can be much better a- about this. We can science the heck out of this." And I love that approach, and so I think the... it's complementary. I'm saying, let's do real science, clinical trials, molecular, uh, but also with an N of one, doing pre-treatment, post-treatment, see what happens under doctor supervision. We can learn some things too. Um, yeah, it, I, I think Bryan deserves a lot of credit for, for that, for bringing attention to what's possible

    7. CWChris Williamson1:33:01

       And look, you've got a, you've got a highly unsexy field.

    8. DSDr. David Sinclair1:33:04

       Yeah.

    9. CWChris Williamson1:33:04

       I'm not saying Bryan Johnson's the sexiest guy on the planet, but he's definitely made a, an existingly unsexy field at least a little bit more sexy. What, uh, knowing what you know about his approach to, um, the fundamentals for longevity, have you got any smell test or sort of lick your finger to work out where the wind is coming from, where you think, "Oh, he might really be onto something there"? Is there something that he might be out ahead of where the, the data or the research or the science is at the moment?

    10. DSDr. David Sinclair1:33:34

        [sighs] Um, not really. I, I, I don't pay as much attention to him as I probably, uh, should or could.

    11. CWChris Williamson1:33:46

        Mm.

    12. DSDr. David Sinclair1:33:46

        Um, I do look at some of the, the blood work that he posts and, uh, there's a particular test, um, that's called the Dunedin Pace of Aging, which is a measurement of your epigenome changing. So we... Steve, in the magazine, Steve Horvath discovered the epigenetic clock. For those of you who don't know what that is, it's chemicals on the DNA that change with time. These are like the scratches on the CD or the software corruption. You can measure that. You can do it before and after, or you take it every, you know, three months or every year. And Bryan has published publicly his results, and you can determine what is representative of your pace of aging. And his was, I recall, something like 0.4 something versus... And one would be you're aging one year for every year.

    13. CWChris Williamson1:34:36

        Yep.

    14. DSDr. David Sinclair1:34:37

        And, you know, if you're two, then you're doubling your rate of aging, so you're gonna die early. According to that, that's one of the lowest paces of aging I've ever seen for a human, so that's pretty impressive. If that's maintained-

    15. CWChris Williamson1:34:49

        Mm

    16. DSDr. David Sinclair1:34:49

        ... he could live decades longer than the average human.

    17. CWChris Williamson1:34:52

        He's supposed to.

    18. DSDr. David Sinclair1:34:54

        Than he would if he didn't take care of himself.

    19. CWChris Williamson1:34:56

        Is that taking into account telomeres or no with that Dunedin Pace of Aging thing?

    20. DSDr. David Sinclair1:35:00

        No, it's not.

    21. CWChris Williamson1:35:01

        Interesting.

    22. DSDr. David Sinclair1:35:01

        No, I don't, I don't believe so. It's, uh, just, uh, looking at the what's called DNA methylation pattern on the DNA.

23. 1:35:09 – 1:39:11

    Are Vitamins a Waste of Money?

    1. CWChris Williamson1:35:09

       What do you think are the biggest wastes of money that people spend on longevity?

    2. DSDr. David Sinclair1:35:14

       Oh, well, the overdosing of vitamins, particularly B vitamins. Um, I think that if you're on a vegan diet, yeah, you should make sure you're not deficient in any B vitamins. Um, generally, if you're taking a lot of multi... uh, what do you call it? Multivitamins, uh, it's excessive, and it can actually be toxic if you have too much. So vitamin C, uh, can be pro-oxidation, not antioxidant, if you take a lot continuously. So overall, I'm not, I'm not for multivitamins. Um, I do believe you should measure your vitamin, uh, in your blood, a- and if you're deficient, you should make sure you're not deficient. But overdosing on vitamins, especially B, you know, you could do IV. Some people do that. I think, yeah, you'll get a short-term hit, but I, I nibble on my B vitamins. I don't s- take the whole thing.

    3. CWChris Williamson1:36:11

       I tried... Again, the self-experimentation over the last couple of years recovering from this, this mold complex illness stuff has been interesting, to say the least. And the start of last year, one of the potential culprits for why I was feeling so shitty was methylation. So I did a bunch of genetic testing, came back, I've got four different polymorphisms that make me suck at B vitamins, like one in the blood, one in the brain, one in the methylation, and one in the something else. One of the potential put forward, uh, explanations was, well, your mean corpuscular volume, your MCV, is high. It's like just at like 101 or whatever, which is just above the upper range. Oh, well, maybe this is something to do with Bs. I was like, okay, well, I'll try some, uh, intramuscular methylated B12.

    4. DSDr. David Sinclair1:36:55

       Mm-hmm.

    5. CWChris Williamson1:36:55

       Like 500 micrograms. So you tiny, tiny... teeny tiny little... It's almost like gotta put a huge needle in your leg to put this teeny tiny amount of B vitamins in. I didn't realize that you can get something if you push it too far called B12 induced confusion. So you can actually just make yourself confused, and your brain gets very slippery. Given that this was the thing that I was trying to push back against, what I'm saying is I know what happens when you push B vitamins too far.

    6. DSDr. David Sinclair1:37:19

       Oh.

    7. CWChris Williamson1:37:19

       Um, and I actually did that the week... It was the biggest week of the show last year where I had Rogan. I was on Rogan on the Thursday and then recorded the Naval Ravikant on the Saturday, and I went into it going, "I've, like, poisoned myself with f- fucking B vitamins, and now I can't think straight." It was fine. It was... It, it all ended up being great in any case. But, uh, yeah, okay. So, um, spending too much money on, uh, vitamins, multivitamins is one of the biggest wastes. What else?

    8. DSDr. David Sinclair1:37:43

       Well, at the risk of being sued, um-

    9. CWChris Williamson1:37:46

       [chuckles]

    10. DSDr. David Sinclair1:37:46

        ... I would say-

    11. CWChris Williamson1:37:47

        That's a big Q

    12. DSDr. David Sinclair1:37:48

        ... I'm not sure about... Again, I'm not saying it's wrong. I'm just not sure about, uh, certain laser therapy. Um, Serena, my partner, loves shooting lasers at her body, but I, I-

    13. CWChris Williamson1:38:03

        For skincare?

    14. DSDr. David Sinclair1:38:05

        Uh, internal as well. So-

    15. CWChris Williamson1:38:07

        How do you shoot a laser internally?

    16. DSDr. David Sinclair1:38:10

        Well-

    17. CWChris Williamson1:38:10

        Which, which hole does it go in?

    18. DSDr. David Sinclair1:38:12

        Yeah, well, it, it shines on your skin back and forth. So I don't know if that is doing anything. I'd like to see some data on that.

    19. CWChris Williamson1:38:18

        Is that like red light stuff?

    20. DSDr. David Sinclair1:38:20

        It's red light, but it's different colors and wavelengths.

    21. CWChris Williamson1:38:22

        Oh, yes. Yeah, I've seen those things, those huge, big panels that people can stand in front of.

    22. DSDr. David Sinclair1:38:27

        Well, the red light is not crazy, so certain infrared. I've got near-infrared panels. I have that actually. I shine that in the shower sometimes.

    23. CWChris Williamson1:38:36

        Okay

    24. DSDr. David Sinclair1:38:37

        And that the science is coming around to confirming some benefits there. So I think that's fine. And the red light saunas, um, I'm gonna get one and see how that goes.

    25. CWChris Williamson1:38:45

        But the yellow lights and the others-

    26. DSDr. David Sinclair1:38:47

        Yeah, these other things. It looks like it's, uh, 4th of July, uh, in, in the house, but I'm not sure about that one. Um, but you know, you have got to be careful what you say is BS now turns out to be true five years from now.

    27. CWChris Williamson1:39:04

        This is where the biohackers get it right, dude. This is where the biohackers get it right.

    28. DSDr. David Sinclair1:39:06

        Yeah.

    29. CWChris Williamson1:39:07

        They-

    30. DSDr. David Sinclair1:39:07

        Even peptides, you know, now we're seeing a lot of them are actually really

24. 1:39:11 – 1:45:53

    Could GLP-1s Protect Against Dementia?

    1. DSDr. David Sinclair1:39:11

       helpful.

    2. CWChris Williamson1:39:12

       Talk to me about GLPs because, you know, this has been-

    3. DSDr. David Sinclair1:39:15

       Yep

    4. CWChris Williamson1:39:15

       ... this wouldn't have even been a discussion, right? Three letters that I'd never have even heard put together the last time that we sat down in two thousand and twenty-one.

    5. DSDr. David Sinclair1:39:23

       Mm-hmm.

    6. CWChris Williamson1:39:23

       And certainly not in twenty nineteen.

    7. DSDr. David Sinclair1:39:25

       Yeah.

    8. CWChris Williamson1:39:25

       What's your opinion on GLPs?

    9. DSDr. David Sinclair1:39:28

       Uh, in general, I'm very favorable. The, the number of studies that, that come out are showing that they're actually quite useful, especially microdosing for healthy people. If you're obese, it, it's, it's almost a must. Go talk to your doctor. I think if you can't lose weight alone, please consider using these. I, I think obesity is the fastest way to, to an early grave. It certainly ages you faster. But if you're, if you're like you and you're already, already close to optimal, are they useful? I think so. The- there are off-target things besides obesity and metabolism that seem to be-

    10. CWChris Williamson1:40:06

        Hmm

    11. DSDr. David Sinclair1:40:06

        ... important. Brain health, um, your immune system. New things are cropping up all the time. It's as close to a longevity drug as we probably have right now given-

    12. CWChris Williamson1:40:16

        Really?

    13. DSDr. David Sinclair1:40:16

        ... what we're seeing. Yeah. It's still early days because we, we need to do long term, and there are some downsides. There is increased risk of, but low, uh, risk of kidney issues and even blindness. Um, don't panic. It's, it doesn't happen very often. So it's still really rare. But there... It's not perfectly safe. So I just want to make sure people know-

    14. CWChris Williamson1:40:36

        Yeah

    15. DSDr. David Sinclair1:40:36

        ... that it's not like going out injecting, uh, candy into you or anything. Um, but I do think that, uh, and I have taken GLP-1s, um, small doses to see how I would feel, what would happen. I definitely didn't have hunger. That was obviously what would happen, and I lost weight more easily. Um, I didn't take it long enough to be able to tell if other things were benefited. It looks like, uh, there's protection against, uh, dementia from those who are on the weight loss drugs.

    16. CWChris Williamson1:41:08

        And this is from a mechanism other than just calorie restriction. There's something else going on.

    17. DSDr. David Sinclair1:41:13

        It's hard to tell, right? Because most of the people on them are already overweight. But yeah, I saw a study recently, um, I don't remember the journal, um, but I'll look it up and, and post it online on my social. Uh, but I did see one that had really good evidence that it was not due to weight loss. It's just, uh, I would say in general, whenever I go to a longevity conference and there's a company, uh, like Novo Nordisk or Lilly, they're like, "You should see this latest study. We've shown that it do- it does this thing that we didn't expect at all-

    18. CWChris Williamson1:41:45

        Hmm

    19. DSDr. David Sinclair1:41:45

        ... as a side effect." Um, and it's funny, these companies are now calling themselves also longevity companies. It's become that fashionable as well.

    20. CWChris Williamson1:41:55

        Well, I suppose anything that, anything that reduces morbidity technically in one form. I mean, people that make helmet, bike helmets are longevity companies, you know?

    21. DSDr. David Sinclair1:42:07

        You're right, and it's, it's a word that's unfortunately getting overused like anti-aging was-

    22. CWChris Williamson1:42:12

        Hmm

    23. DSDr. David Sinclair1:42:12

        ... thirty years ago, and we'll have to come up with something else to distinguish.

    24. CWChris Williamson1:42:15

        I'm sure we'll come up with something sexy.

    25. DSDr. David Sinclair1:42:16

        Yeah.

    26. CWChris Williamson1:42:16

        Huberman says he thinks retatrutide will be a trillion-dollar drug. Do you reckon about that?

    27. DSDr. David Sinclair1:42:24

        Um, I think it's possible. Uh, if the oral ones really look good, they, they may actually be, uh, even more interesting. But yeah, what is it? Something like ten percent of Americans have either tried it or been on these drugs or-

    28. CWChris Williamson1:42:39

        I think forty-five percent of Americans say that they would. Jerry, can you, uh, ChatGPT whatever the, the numbers are of GLP users and desired, uh, users in the USA? Let's find that out. Uh, but yeah, I mean, what is it? Obesity is twice as big of an issue as malnu- as, uh, as starvation now globally. There's a billion people that are obese and half a billion people that are starving. It's like the number one leading cause of malnutrition globally is obesity. Currently, around about eleven percent of US adults, twenty-nine million Americans ever used a GLP, fifteen percent. So that means that only, what's that? About two-thirds of people who have used one are currently using one. And ninety-one percent of Americans are aware of them. Uh, twenty percent of US households... Can you say, uh, how many people want to? Uh, I'm sure that this was from, uh, the most recent book that Johann Hari brought out, saying that it's like forty-five percent of Americans would either have tried or want to try them. About forty percent of US adults have obesity from... Yeah, um, we'll say that my number is correct.

    29. DSDr. David Sinclair1:44:01

        Yeah.

    30. CWChris Williamson1:44:02

        Cool.
25. 1:45:53 – 1:54:00

    What’s AI Doing to Longevity Research?

    1. CWChris Williamson1:45:53

       What common health advice today do you think people will laugh at in 50 years' time?

    2. DSDr. David Sinclair1:46:01

       Uh, yeah, I think that, uh, eating three meals and snacking, that this... You go to the, you go to the supermarket, and there's health bars down the whole aisle, aisle, that you're supposed to never be hungry. That's gonna be seen as extremely toxic. You, you, your body needs to feel hungry sometimes, uh, have a break from food. So this, this trend of you're a bad parent if your child feels hunger is gonna be looked at like, "Oh, what were we doing to our kids?"

    3. CWChris Williamson1:46:31

       Hmm. Mm-hmm. Do you think AI is going to make bigger inroads into longevity research? I don't know what... I mean, again, you know, seven years ago when we sat down, AI w- you, with your snail, your drawing of a fucking snail on the whiteboard, there was no AI to be found.

    4. DSDr. David Sinclair1:46:48

       Yeah. I don't remember what the snail was, dude.

    5. CWChris Williamson1:46:50

       I asked you about it at the time, and it was something to do... It was explaining... It was some nerd stuff. This is how the molecular something, something.

    6. DSDr. David Sinclair1:46:57

       Oh, I remember. We, we, we said, "Chris is coming. Let's draw a snail for no reason."

    7. CWChris Williamson1:47:01

       Draw a fucking snail. He's the idiot British guy. We'll get him in-

    8. DSDr. David Sinclair1:47:04

       [laughs]

    9. CWChris Williamson1:47:05

       ... and he'll be convinced that it's actually something really important. What's AI doing to longevity research?

    10. DSDr. David Sinclair1:47:09

        Yeah. Well, you asked me do I think. I know it's having a big imp- impact already on research. My lab is thriving on it. It's going way faster. We just did something in a few months that would've taken us 160 years, and that was l- That's using old technology. These days we can do... I'll tell you, I'll tell you a story that's funny. On Friday, I had a meeting with a student that just came to my lab over the summer, and he's been here maybe three weeks, and he's 19 years old. And I gave him a task. I said, "According to the information theory of aging, if you look at all this data that's out there that nobody's looked at in a certain way, it should have this signature. And, uh, and if it has that signature, we might be right. We might have found the backup copy to the software." And I said, "Okay, that, that's your task. Go, go do that," thinking, you know, how-

    11. CWChris Williamson1:48:02

        Keep him busy for-

    12. DSDr. David Sinclair1:48:03

        It'll take him months

    13. CWChris Williamson1:48:03

        ... the next five years. Yeah.

    14. DSDr. David Sinclair1:48:04

        Exactly, because I've had about three people in my lab try to do that, and they were not really successful. And he came in on Friday, uh, and he's with his team and his mentors, and we sat in my office, and they've all got this big grin on their face, and they threw up on the LCD screen in my office the results. And this wasn't just the usual, "I wrote some code in R and ran it and, and we got some graphs." This was truly using AI. He was using one of the, the, the, the leading AI models. And he presented it like it was already published work with beautiful graphs and looking at terabytes of data that's out there in a new way. And he found something that professors and the experts in the field have missed for the last 10 years, and it's right there. There's this signature. He goes, "I've given it a new name because I didn't know what to call it. This signature, I'm calling it the reverse tail." I said, "What the heck is a reverse tail?" And he said, "Uh, well, I called it this because of that." And I said, "Dumb name. We'll think of a new name for it." But it's amazing.

    15. CWChris Williamson1:49:07

        Love the idea, shit branding.

    16. DSDr. David Sinclair1:49:09

        Yeah. We'll work on branding later. But the fact that you found it is incredible. And that's a 19-year-old, uh, I think he just finished high school, and with AI, he's gonna revolutionize biology, I believe, and that's just one kid. Imagine when whole teams are doing this.

    17. CWChris Williamson1:49:25

        That's wild. That's wild. So have you... Has there been anything as far as you're aware in the field of longevity that's been, uh, generated or inspired by AI that has gotten itself to trials, testing, and, and fully published as a, a world change, or is, are we still at the frontier of that not really me- meeting the real world yet?

    18. DSDr. David Sinclair1:49:48

        Oh, we, we're, we're undergoing this revolution, so tomorrow's going to be better than yesterday. But we're now at a point where almost somebody on their phone can discover a drug candidate.

    19. CWChris Williamson1:50:02

        Hmm.

    20. DSDr. David Sinclair1:50:02

        Whereas it would have taken a pharmaceutical company years, uh, and hundreds of millions of dollars. It's that world. We can go from... Now that, um, uh, Demis Hassabis has, and his team, not just him, has cracked the code for protein folding, we now know all the chess pieces. We were guessing, and it took years to find out what one chess piece looked like. And there's, uh, over 15,000 of these pieces now. These are all now modeled in 3D. Now we know not just how they look in 3D because they used to be one-dimensional based on the DNA. Now we've got three-dimensional amino acid structures. Now we're seeing how they fit together. Computer is actually smart enough to figure out which ones dock with each other, and eventually we'll figure out how they're all working together, uh, an artificial AI version of a cell. We can Do in silico experiments at the molecular level now and dock trillions, last year it was billions, now this year it's trillions of chemicals, real drugs and imaginary drugs

    21. CWChris Williamson1:51:08

        It's kind of like a virtual environment.

    22. DSDr. David Sinclair1:51:09

        Yeah.

    23. CWChris Williamson1:51:09

        It's like a virtual lab.

    24. DSDr. David Sinclair1:51:11

        Yeah.

    25. CWChris Williamson1:51:11

        Are these accurate? So if I run the synthetic lab, is it one-to-one with the real world?

    26. DSDr. David Sinclair1:51:19

        It's not one-to-one, but it, it increases your odds exponentially

    27. CWChris Williamson1:51:23

        Because you don't need to do test, test, test, okay, maybe this. You can discount a lot, and then the interesting ones get moved into the real world?

    28. DSDr. David Sinclair1:51:30

        Yeah. Yeah. And, and the old way of doing it, which felt really modern, was you have libraries of little plates, hundreds of these little plates with 96 or sometimes 384 little wells, and each one has a different chemical that's physically in a freezer somewhere. You have to pull it out, give it to the robot. The robot then does its work overnight, tests it on cells, take a picture of the cells. You know, this kind of work is, is, is slow compared to today, which is we don't even need to have the fridge. We can make up trillions of potential drugs, test them, run it for a few weeks. It'll tell us, "Here's the top 200," and probably at least half of them are pretty good.

    29. CWChris Williamson1:52:12

        It feels fucking primitive.

    30. DSDr. David Sinclair1:52:14

        And now we can do that experiment with hundreds instead of trillions.
26. 1:54:00 – 1:56:24

    Can Your Mindset Affect How Long You Live?

    1. CWChris Williamson1:54:00

       How big of a role is expectation in how someone lives? If somebody thinks about aging as being associated with frailty and degeneration, can that actually make them live less long?

    2. DSDr. David Sinclair1:54:12

       Oh, you mean mentally? If they're-

    3. CWChris Williamson1:54:14

       Sure

    4. DSDr. David Sinclair1:54:14

       ... Yeah. That's well-studied. If you're optimistic and you're enjoying life and you don't just get retire- just retire and be bored, um, yeah, mental attitude is huge. Um, Robert Waldinger, a Harvard scientist, has found that the mental attitude and your social life is as important as your blood pressure and cholesterol, if not more important. And the one thing that was the best was have a reliable partner. I went through a divorce. It was horrific, uh, during COVID, and I believe that it took years off my life, so it felt like it anyway. But, uh, it was a, it was a shock. I didn't know it was coming. But, uh, it's brutal. Um, anyone that is young getting married, just beware. Um, we all change over decades, so that's, uh, something to keep in mind. But the point there is, uh, the amount of stress and cortisol that runs through your body when you have a really big life event, moving house, breakups, uh, death in the family, your own illness, these are age accelerators. And on the other hand, we've talked about today the kind of things that keep you healthy. Um, the exercise, the diet, the social life, the sleep, the relaxation, these are all we know, um, are likely to not just slow aging, but eventually keep you disease-free. And I do, I do want to mention that often people think, "Oh, I don't want to live longer because I don't want to be old for longer."

    5. CWChris Williamson1:55:36

       Mm.

    6. DSDr. David Sinclair1:55:37

       That's not what we're talking about. We're talking about still being young and vigorous in your 90s. My father's almost 90. He's 87 now. He'll be here on Friday from Australia. It'll be, I think, second or third time he's come to the US. He was just in Japan. This is not a typical 87-year-old. He is living life probably better than he did in his 40s. He's out every night with different people, mostly, uh, uh, women that he's excited about. Um, no they're good friends. I wouldn't-

    7. CWChris Williamson1:56:06

       Mm. [laughs]

    8. DSDr. David Sinclair1:56:06

       I don't want to disparage my father. He's not a dirty man. But, um, he, he is a very sociable guy, and in his 40s, he was raising me, and I wasn't easy to, to raise. I was a pain in the butt. He will, he will say he's never had a better time in his life than now at 87.

27. 1:56:24 – 1:57:31

    The Two Things That Matter Most for Longevity

    1. CWChris Williamson1:56:25

       If you were 35 or 40 again and you could only do two or three things for longevity, what would they be?

    2. DSDr. David Sinclair1:56:32

       Um, definitely don't overeat. Be lean. Watch your weight. Have a BMI of around, let's say, 20 to 24. Make sure you, you don't get overweight. Um, obviously don't over-drink and don't smoke. These are clearly really the worst things you can do, having lost a mother to smoking. Um, so don't eat too much, right? Try to skip meals. Uh, work out, maintain a very good- Body mass, um, and exercise. Those are the fundamentals. Everyone will tell you that. Um, what I didn't realize till I was in my 50s was how important food is. I thought vegetables were a garnish for meat. I love meat. Um, they taste... Meat tastes great. But I've, I've switched over to being more plant-focused, and I've seen a great improvement in my overall health and biomarkers.

    3. CWChris Williamson1:57:20

       Mm.

    4. DSDr. David Sinclair1:57:21

       So those are good. Learn not to stress, we've talked about. Um, that took me a long time to, to learn that as well. But I've never been healthier because I've... It's been slow, but I've learnt how to do all these things really well.

28. 1:57:31 – 2:03:02

    Which Longevity Methods Actually Work?

    1. CWChris Williamson1:57:31

       I want to do a lightning round. So in a sentence or two, give me your review on these interventions for longevity. Okay?

    2. DSDr. David Sinclair1:57:37

       Okay.

    3. CWChris Williamson1:57:38

       Creatine.

    4. DSDr. David Sinclair1:57:38

       We doing... How we, how we scoring?

    5. CWChris Williamson1:57:41

       Just however you want. Give me a review. Yes, no, like it, don't like it, useless, buy it, do whatever you think, whatever you don't.

    6. DSDr. David Sinclair1:57:47

       Okay. All right. So creatine, um, in favor of it and take it.

    7. CWChris Williamson1:57:53

       Stem cells.

    8. DSDr. David Sinclair1:57:55

       Interesting, and if you have a certain condition like a, a joint that needs repair, can be helpful, but it's not long-term solution.

    9. CWChris Williamson1:58:06

       CPAP machine.

    10. DSDr. David Sinclair1:58:08

        Really important, um, for folks that have anoxia, lack oxygen at night for the brain. Um, though you could try other methods, which is lose weight, um, don't drink, uh, get a thin pillow, try to sleep on your stomach.

    11. CWChris Williamson1:58:23

        Hyperbaric oxygen therapy.

    12. DSDr. David Sinclair1:58:25

        Uh, in favor. There's good evidence that certainly cycling, uh, up and down in pressure is good for the brain and blood flow, and, uh, have done it myself and, uh, have seen improvements in wound healing in others. So yeah, in general, it's, it's a plus.

    13. CWChris Williamson1:58:41

        Blue light glasses.

    14. DSDr. David Sinclair1:58:44

        Yeah. Uh, y- you mean yellow, uh-

    15. CWChris Williamson1:58:48

        Blocks

    16. DSDr. David Sinclair1:58:48

        ... blue light blocking glasses? Um, I prefer to turn down the brightness of the lights at night and have a TV that's not so bright. But yes, I think they were much more fashionable five years ago, but I still use them, so yes. But definitely in general, watch out for bright light at night, but try to get violet and blue light in the morning. It's very important. A friend of mine in Japan found that if you don't see violet light, uh, and you're a mouse, you get, uh, shortsightedness.

    17. CWChris Williamson1:59:20

        So early morning light can be, uh, protective, like for your eyes?

    18. DSDr. David Sinclair1:59:24

        Yeah, yeah. And we live indoors, and we, we don't get enough of it from LEDs.

    19. CWChris Williamson1:59:28

        Okay. Glucose monitors.

    20. DSDr. David Sinclair1:59:29

        Love 'em.

    21. CWChris Williamson1:59:30

        Why?

    22. DSDr. David Sinclair1:59:30

        They're really good. Yeah, I, I, I think that we should all be empowered by our own data. Um, anyone who says, "I don't want to know about my biology," I think, uh, I don't agree with that. The CGMs have been very useful personally. I can see how I react to foods, and I was surprised. Um, grapes send me through the roof, white rice through the roof.

    23. CWChris Williamson1:59:51

        I remember the grape thing. You told me about that last time.

    24. DSDr. David Sinclair1:59:52

        Potatoes not. Yeah. And it's still true. I'm wearing one right now. I wear them fairly regularly. The other thing that surprised me about CGMs was I gave one to my son, who at the time was, I think, 17, and we had a competition, who can, uh, have the best blood glucose levels, and he would eat a lot of bad stuff. It changed his life. He is eating much healthier. He's now aware of what food does to his body. Now, I'm not saying go give it to children, but I do think there's an education and a behavioral change that can come with CGMs that, as I think you mentioned earlier today, can really, really make a difference.

    25. CWChris Williamson2:00:30

        Therapy.

    26. DSDr. David Sinclair2:00:31

        You mean just general, uh, psychology?

    27. CWChris Williamson2:00:35

        Talk therapy, psychotherapy.

    28. DSDr. David Sinclair2:00:37

        Well, I think it, it depends on the person and the therapist. Um, I think that talking about your problems can really help. Um, I think it can be overused. Um, as a friend, um, I've, I've tried everything. Um, I didn't find a lot of the therapists to be that useful. I found it better to read books and listen to experts and... Um, but I do think therapy is very important. I've, um, had kids that benefited from therapy. It's very hard being-

    29. CWChris Williamson2:01:07

        Mm

    30. DSDr. David Sinclair2:01:07

        ... a teenager these days, uh, with the pressures. So yeah, a thumbs up for therapy, though, make sure you have a therapist that is well qualified and provides benefits rather than just listens to your complaints.
29. 2:03:02 – 2:04:48

    When Health Optimisation Goes Too Far

    1. CWChris Williamson2:03:02

       How do you... You talked in- a lot today about Supplements, lifestyle interventions, rest, recovery, what the future's gonna look like, AI, GLPs. Something that we never got to talk about when me and, me and you first sat down were the perils of over-optimization. I think that it was so frontier-y in 2019. Z- everything was new and exciting, and you couldn't really be drowning in data in the same way as you can now.

    2. DSDr. David Sinclair2:03:27

       Mm-hmm.

    3. CWChris Williamson2:03:27

       And I wonder what you've come to believe about the negative health implications of caring too much about your health, of over-optimizing, the neuroticism taking away not only your enjoyment from life, but the effects of supposedly all of the interventions that you're actually trying to do.

    4. DSDr. David Sinclair2:03:50

       Yeah.

    5. CWChris Williamson2:03:50

       How do you come to think about over-optimization?

    6. DSDr. David Sinclair2:03:53

       Well, obsession about anything is possible and also deleterious to health. Uh, so if you have those tendencies, be careful. You know, it's true for anything, social media use as well. Um, and I, I can be o- obsessed. What, what I've done myself, which I recommend, is treat it like a hobby. It's fun. It's not too serious. You're not gonna die if you didn't sleep well last night. Um, and, you know, everything's challenge. Uh, my meals are an experiment. Um, not always. Sometimes it's a failed experiment. Um, but I live my life like it's a journey, and it's fun, and I'm testing things. Um, and so don't get too obsessed if you are not perfect when none of us are ever perfect.

    7. CWChris Williamson2:04:42

       Right.

    8. DSDr. David Sinclair2:04:42

       And none of us are gonna live forever, in my opinion. So enjoy the journey. Do as best you can.

30. 2:04:48 – 2:05:40

    Where to Find David

    1. DSDr. David Sinclair2:04:48

       Don't stress.

    2. CWChris Williamson2:04:49

       Heck yeah. David Sinclair, ladies and gentlemen. David, you're awesome. I appreciate you seven years later. Where should people go to check out everything that you've got going on?

    3. DSDr. David Sinclair2:04:56

       Uh, well, the big one is lifespan.com. Become a member, get the magazine, learn how to live longer, and we'll learn together. We'll do some big things together. Um, and I'm on social media. You can see what I do.

    4. CWChris Williamson2:05:08

       Your podcast season?

    5. DSDr. David Sinclair2:05:09

       Podcast is big. Uh, so that's on YouTube and all, all podcast. Uh, that's called Lifespan with Dr. David Sinclair. We have... We're building. We're about half a million followers, not like you, but-

    6. CWChris Williamson2:05:19

       You're alright

    7. DSDr. David Sinclair2:05:20

       ... we'll get there.

    8. CWChris Williamson2:05:20

       You're doing good.

    9. DSDr. David Sinclair2:05:21

       We did take some time off to do the trials, but we're back and, uh, even better now. So join us there too. Thank you, Chris.

    10. CWChris Williamson2:05:27

        Heck yeah. Appreciate you, mate.

    11. DSDr. David Sinclair2:05:28

        Likewise.

    12. CWChris Williamson2:05:28

        Till next time. All right. Goodbye, my beauties. Dude, yes. So good. Congratulations. You made it to the end of a podcast episode without dying. Now, here's another one. Go on, watch it.

Episode duration: 2:05:41