Joe Rogan Experience #1234 - David Sinclair

1. 0:01 – 1:10

   Can aging be slowed—or reversed? Setting the stakes for longevity science

   1. JRJoe Rogan0:01

      Here we go. Five, four, three, two, one. David.

   2. DSDavid Sinclair0:08

      Joe.

   3. JRJoe Rogan0:09

      How are you, sir?

   4. DSDavid Sinclair0:10

      Great. Thanks.

   5. JRJoe Rogan0:10

      Thanks for being here, man. I appreciate it.

   6. DSDavid Sinclair0:12

      Hey, thanks for having me on.

   7. JRJoe Rogan0:13

      Really looking forward to talking to you. Very much so.

   8. DSDavid Sinclair0:16

      Well...

   9. JRJoe Rogan0:16

      Um, this is a fascinating subject for me. Anti-aging. The idea that you'll be able to stop aging, or even possibly pull it back, or at v- very least slow it down. What do you think?

   10. DSDavid Sinclair0:29

       I think that's all on the table. We've been doing this for years in the lab. Now we've just got to figure out how to do it in people.

   11. JRJoe Rogan0:33

       When I talk to someone like you as an actual research scientist in this stuff, I always want to know, what are you doing to yourself?

   12. DSDavid Sinclair0:39

       Ah. How long have you got? (laughs)

   13. JRJoe Rogan0:42

       (laughs) Like, what do you do on a daily basis?

   14. DSDavid Sinclair0:43

       What do I do? I'm-

   15. JRJoe Rogan0:44

       First of all, are you 100 years old?

   16. DSDavid Sinclair0:46

       Uh, getting there.

   17. JRJoe Rogan0:47

       How old are you?

   18. DSDavid Sinclair0:47

       Uh, turning 50. So...

   19. JRJoe Rogan0:49

       Oh, you're turning 50? Hmm.

   20. DSDavid Sinclair0:50

       Yeah.

   21. JRJoe Rogan0:50

       I wouldn't have thought you were 50. I would've figured you were for about 41, 42.

   22. DSDavid Sinclair0:56

       Oh, that's kind of you. Um-

   23. JRJoe Rogan0:57

       Hmm.

   24. DSDavid Sinclair0:57

       Well, my brother's the negative control and he's, he's, uh...

   25. JRJoe Rogan1:00

       Does he look like shit?

   26. DSDavid Sinclair1:01

       Well, I can't say that, but, uh...

   27. JRJoe Rogan1:04

       (laughs)

   28. DSDavid Sinclair1:04

       People say that he doesn't look as young as me and he's about three and a half years younger.

   29. JRJoe Rogan1:07

       Oh. So what are you doing personally?

2. 1:10 – 4:03

   Sinclair’s personal longevity routine: fasting, supplements, and lifestyle stressors

   1. DSDavid Sinclair1:10

      Uh, well, you know, most of the time, I'm in the lab and trying to run a bunch of companies to make these drugs a reality. Uh, but daily, you know, I try to keep a healthy weight. I do intermittent fasting, uh, which is pretty easy, 'cause I'm so busy, I forget to eat.

   2. JRJoe Rogan1:24

      How many hours do you give yourself per night?

   3. DSDavid Sinclair1:26

      Uh, well, I suffer from, uh, late night snacking, but I try to skip breakfast and, and even skip lunch if I'm busy. So I'm a night eater. Um, but that seemed to be good, 'cause a, a study came out about a couple of weeks ago, at least in mice, that it's not what you eat, it's when you eat that's most important for longevity.

   4. JRJoe Rogan1:43

      Really?

   5. DSDavid Sinclair1:43

      Yeah.

   6. JRJoe Rogan1:43

      And when, when being when? Like what's best?

   7. DSDavid Sinclair1:47

      Well, I, it doesn't actually matter, uh, if you eat a lot in the morning or a lot at night. I like nighttime eating. But you need a period during the day, at least if you're a mouse, probably if you're a human, where you're hungry. Um, and that puts your body in a defensive mode. And these, these are the things that we've been studying in my lab for the last 20 years. What are the processes that diet and exercise do for us that keep us healthy, and why does calorie restriction and intermittent fasting make animals live so much longer? And we think we've figured out a large part of how that works, and now we're mimicking that with molecules.

   8. JRJoe Rogan2:20

      Um, is the m- is the idea that you can mimic it with molecules and it'll be as effective as intermittent fasting?

   9. DSDavid Sinclair2:28

      I think the molecules will be better. Um, and not only that, when we add them onto a healthy diet and exercise in the animals, they do even better. It's like a supercharged mouse.

   10. JRJoe Rogan2:37

       Now, when you add them onto the mice, do you also add them on with intermittent fasting, and is there an additional benefit?

   11. DSDavid Sinclair2:44

       Uh, we do. We do. Uh, one of the first molecules that, uh, infamous molecules that we, uh, are known for is resveratrol, from red wine. That molecule, discovered it in my 30s, or at least linked it to aging. What we showed was that if you give it to a fat mouse, they're as healthy as a thin mouse. Uh, they live just as long, they didn't get heart disease and all of the other bad stuff. Then what we did was interesting. We gave it to the mice either every day in their food, or let them skip a meal every day, so that they were fed every other day. And that combination of resveratrol plus every other day feeding, we had the longest lifespan we'd ever seen. And it was always additive. Same with exercise. If we give our latest molecule called NMN, uh, to a mouse, and we exercise it, it'll run even further than it could with either of those alone. So it's not an excuse to sit around and just eat chips and watch TV. It augments a healthy lifestyle. It gets you further than what you could get naturally.

   12. JRJoe Rogan3:40

       So in, in the, are you seeing a benefit in addition? So is the idea to compound all those things together?

   13. DSDavid Sinclair3:47

       Exactly. Right. So you asked about myself. So I, I do, I eat healthy. I try to skip meals. Uh, I also take supplements. Um, and in fact, most of my colleagues are, in the field of aging, or anti-aging, as, as people call it. Uh, so I take NMN every morning.

3. 4:03 – 7:08

   Resveratrol, NMN/NR, NAD: the ‘fuel and accelerator’ model for sirtuins

   1. JRJoe Rogan4:03

      What is NMN?

   2. DSDavid Sinclair4:04

      Good question. So let me take a quick step back.

   3. JRJoe Rogan4:07

      Oh, sure.

   4. DSDavid Sinclair4:08

      Uh, so about 20 years ago, uh, Lenny Guarente and a team of us at MIT discovered a set of genes that controls aging in yeast cells. Just brewer's yeast, what you find in beer and bread. And those genes are called sirtuins, and there are seven of them in our bodies, five in yeast. And what they do is they protect all organisms on the planet, plants, bacteria, humans, from deterioration and disease. They're like the Pentagon. They sense when we're hungry, sense when we're exercising, and they send out the troops to defend us. So when you, when you put more of these genes into a yeast cell or, or a mouse, they'll live longer. Between, oh, five to 20% longer. And so we think that these genes are responsible for the effects of dieting and exercise, which is great, which what that means is we can now mimic that with molecules. So NMN is one of those molecules. So is resveratrol. You can think of resveratrol as the accelerator pedal for the sirtuin genes. And the NMN is the, is the fuel. And without fuel, resveratrol won't work. So NMN is the f- the gas in the car.

   5. JRJoe Rogan5:08

      I've heard of resveratrol.

   6. DSDavid Sinclair5:09

      Yeah.

   7. JRJoe Rogan5:09

      But is NMN a new molecule? Is this commercially available?

   8. DSDavid Sinclair5:12

      Uh, some people have started selling it on the internet. Um...

   9. JRJoe Rogan5:15

      The fucking internet.

   10. DSDavid Sinclair5:16

       It's related to, uh, NR, which is sold by a bunch of companies. Uh...

   11. JRJoe Rogan5:21

       NR?

   12. DSDavid Sinclair5:22

       Yeah. Nicotinamide riboside is a supplement that raises the levels of a molecule called NAD.

   13. JRJoe Rogan5:27

       I feel like I should make a shopping list.

   14. DSDavid Sinclair5:30

       So the... (laughs)

   15. JRJoe Rogan5:31

       (laughs)

   16. DSDavid Sinclair5:32

       Get a pen. So while, while you're writing that down, Joe, so the sirtuins. Okay, get this. So sirtuins need NAD...

   17. JRJoe Rogan5:40

       Mm-hmm.

   18. DSDavid Sinclair5:40

       ... to work. Without them, uh, they don't work. In fact, if you don't have NAD in your body, you'd be dead in about 30 seconds. It's a really important molecule. But as we get older, we lose NAD. So by the time you're 50, like I almost am, you have about half the levels of what's- what you had when you were 20. So that's not good. And these sirtuins, they don't protect the body without high levels of NAD. So what NMN does, and this other molecule called NR, which both you can get on the internet, they...... boost the body's levels of NAD back up to youthful levels again. And if we give them to mice, uh, these molecules to, to mice or even to worms or yeast, they live longer and they're super healthy.

   19. JRJoe Rogan6:19

       Now, what level, like, how many milligrams are you taking of these things?

   20. DSDavid Sinclair6:24

       Uh, so yeah, NMN is, is, um, something I, I get from, for myself. I'm not selling anything. So I take a gram of NMN in the morning based on clinical trials that have been shown that that will raise NAD.

   21. JRJoe Rogan6:36

       With or without food?

   22. DSDavid Sinclair6:37

       Um, I take a little bit of yogurt that I make myself at home just to st-

   23. JRJoe Rogan6:41

       Look at you.

   24. DSDavid Sinclair6:41

       ... still me. Uh, yeah, I've been doing this for a while. Uh, and, uh, I only start doing stuff when I see it work in animals first. So take, take the yogurt, mix in some resveratrol. Resveratrol is great, but it's really insoluble. It's like brick dust. So in the yogurt, it'll dissolve. Take another half a gram of resveratrol.

   25. JRJoe Rogan6:59

       And how much, uh, half a gram?

   26. DSDavid Sinclair7:01

       Yeah. It's, it's a, it's a powder. I have a few kilos left over from clinical trials in my basement.

   27. JRJoe Rogan7:07

       (laughs)

4. 7:08 – 13:26

   Metformin, AMPK, mTOR: three major longevity pathways—and why rapamycin is risky

   1. DSDavid Sinclair7:08

      Uh, so yeah, that, that's gonna last me a few decades. Uh, and then I also take, at night, some metformin, which is probably the most radical thing that I take, which is a, a prescribable drug for diabetes.

   2. JRJoe Rogan7:19

      Netformin?

   3. DSDavid Sinclair7:20

      Met.

   4. JRJoe Rogan7:20

      Met, M?

   5. DSDavid Sinclair7:21

      M-E-T.

   6. JRJoe Rogan7:22

      And prescribable drug? So you, but you don't have diabetes?

   7. DSDavid Sinclair7:26

      I do not.

   8. JRJoe Rogan7:27

      But you take it for-

   9. DSDavid Sinclair7:30

      For preventing cancer, heart disease, Alzheimer's, and aging.

   10. JRJoe Rogan7:34

       Metfor- can you spell it? M-E-T-

   11. DSDavid Sinclair7:36

       F-O-R-M-I-N.

   12. JRJoe Rogan7:40

       Oh.

   13. DSDavid Sinclair7:40

       Uh, and so out of studies of 10,000 people and more, it's been shown that people who take metformin, even if, even if they have diabetes, are protected against other diseases of aging, even frailty. And so, m- most scientists, if you ask them in my field, will say, "Yeah, metformin is likely to extend your lifespan." It's just that the FDA doesn't let you have it for aging 'cause aging isn't a disease yet.

   14. JRJoe Rogan8:02

       So do you have to get diabetes to get it?

   15. DSDavid Sinclair8:05

       (sighs)

   16. JRJoe Rogan8:05

       Or do you have to get a sneaky doctor?

   17. DSDavid Sinclair8:06

       Well, I wouldn't call it a sneaky doctor, but the doctor typically has to be convinced 'cause they don't keep up with the literature.

   18. JRJoe Rogan8:11

       Right.

   19. DSDavid Sinclair8:12

       And it's, it's off-label.

   20. JRJoe Rogan8:13

       Okay.

   21. DSDavid Sinclair8:13

       Right.

   22. JRJoe Rogan8:14

       And how much do you take of that?

   23. DSDavid Sinclair8:15

       Uh, I take a gram of that as well.

   24. JRJoe Rogan8:17

       Wow.

   25. DSDavid Sinclair8:17

       Which is about a, a low dose. Uh, some diabetics take two grams, so it's not crazy amounts.

   26. JRJoe Rogan8:22

       Is there any side effects?

   27. DSDavid Sinclair8:23

       Well, the good news is that it's extremely rare that you get sick from any of these molecules. Um, in millions of patients around the world, nobody's getting sick. The worst you'll have, as far as I can tell, is a stomach upset. Um, and I get that, which is actually helpful. If I'm hungry, I, I lose my appetite. But, uh, I, I think the downside is extremely low, and the, the upside is, you know, anything's better than what's coming.

   28. JRJoe Rogan8:50

       And what is the mechanism that metformin is operating under?

   29. DSDavid Sinclair8:54

       Okay. So that, so this is the great thing, is that over the last 20 years, we have figured out, we scientists have figured out that there are universal regulators of aging, from yeast to worms to mice and in humans. And there are three main pathways that we figured out respond to what we eat and how we exercise. And one of them is called AMPK, uh, and this is, uh, a target of metformin. And so I'm active, when I take metformin, I'm activating my AMPK, which will send out the troops. Uh, the sirtuins I've mentioned. That's the second of the pathways. And so I take NMN and resveratrol for that. And then the third one is called mTOR, which is a pathway in the body that responds to how many amino acids, how much meat you're eating. Uh, and it will also protect the body if you tweak it just the right way. And there's only one, besides eating low amounts of protein, the only way to, to affect that pathway is with a drug called rapamycin, which is, which is a little dangerous to try and is, is used for, uh, immunosuppressants. So it's not-

   30. JRJoe Rogan9:56

       Huh.
5. 13:26 – 1:13:06

   Protein, red meat, and performance trade-offs: mTOR, BCAAs, and ‘disposable soma’

   1. JRJoe Rogan13:26

      Ah. Interesting. Interesting. So low carb, low sugar. Um, any specific type of protein? Do you limit your amount of protein?

   2. DSDavid Sinclair13:36

      Yeah. I mean, uh, uh, I enjoy eating mammals just as much as anybody, but, um, I try to avoid them, um, for the main, well, two main reasons. One is that, uh, there's this TMAO molecule that seems to cause heart disease, um-

   3. JRJoe Rogan13:49

      TMAO?

   4. DSDavid Sinclair13:50

      Yeah.

   5. JRJoe Rogan13:51

      Yeah. Um, and how is it linked to heart disease?

   6. DSDavid Sinclair13:55

      Um ...

   7. JRJoe Rogan13:57

      In these epidemiology studies?

   8. DSDavid Sinclair13:59

      I forget, but I, I do recall that the study was able to give the TMAO to animals, and they developed heart disease.

   9. JRJoe Rogan14:06

      Hmm.

   10. DSDavid Sinclair14:06

       So it's somehow causing it. I forget exactly how. It might be damaging the genome. That's my recollection.

   11. JRJoe Rogan14:11

       With, uh, omnivores or predators?

   12. DSDavid Sinclair14:15

       Uh, I think it's red meat is the culprit.

   13. JRJoe Rogan14:18

       Right. So were they giving this to rats or were they giving this to-

   14. DSDavid Sinclair14:21

       It was a mouse study again.

   15. JRJoe Rogan14:22

       Mm.

   16. DSDavid Sinclair14:22

       So, I mean, mice might be different from humans, of course.

   17. JRJoe Rogan14:24

       Yeah.

   18. DSDavid Sinclair14:25

       Uh, but the other problem with, with meat in general from, from animals is that there's a lot of aminos in there, and it's easy to eat a lot of meat. Uh, and so if you have high levels of amino acids, it will activate this mTOR pathway, one of those three longevity pathways, and you don't want that.

   19. JRJoe Rogan14:43

       You don't want that?

   20. DSDavid Sinclair14:43

       You don't want that 'cause mTOR has evolved to sense times of adversity and stress and hunger.

   21. JRJoe Rogan14:49

       So why do people see a performance benefit when they consume branched-chain amino acids?

   22. DSDavid Sinclair14:55

       Ah, really good question. So in the short run, just like taking testosterone, it will give you performance benefits. But we think in the long run, uh, it'll actually come back to bite you.

   23. JRJoe Rogan15:08

       So how will bland- branched-chain amino acids come back to bite you?

   24. DSDavid Sinclair15:11

       So branched-chain amino acids will activate this mTOR pathway.

   25. JRJoe Rogan15:14

       Mm-hmm.

   26. DSDavid Sinclair15:15

       Um, and when we do that in animals, we actually, we reduce their lifespan. So it's the opposite. You wanna keep those levels low.

   27. JRJoe Rogan15:24

       That's interesting. That, that seems s- I mean, for a dummy like me, it seems counterintuitive 'cause, uh, what's making you perform better currently, you would see, you would think especially something like amino acids, a natural part of the human body, you would think that that would be beneficial. You're adding to your body-

   28. DSDavid Sinclair15:40

       Yeah.

   29. JRJoe Rogan15:40

       ... something that it needs.

   30. DSDavid Sinclair15:41

       Yeah, you would. But, but what you should consider is that it's a trade-off. Uh, there's a, a theory that's probably correct. Uh, it's the, uh, some Tom Kirkwood's the- theory called the disposable soma. And our bodies wanna do one of two things. We either wanna grow really fast and reproduce fast, build up a lot of muscle, cells divide. That's great in the short run. Y- you know, you'll be fertile, you can run, but actually, that's at the expense of hunkering down and building a long-lasting body.
6. 22:19 – 29:10

   Young blood, startups, and treating aging as a disease—plus the overpopulation debate

   1. DSDavid Sinclair22:19

      And that's why if you fuse an old mouse to a young mouse, you can have these benefits that the young mouse imparts on the old and actually negatively vice versa.

   2. JRJoe Rogan22:27

      And when you say f- by fuse, you mean by taking the blood of the old mouse and putting into the- the young mouse?

   3. DSDavid Sinclair22:32

      Right. But what we- what we actually do, 'cause that's too hard, um, you can do it in humans, but in mice, what you do is you sew the skin together so that-

   4. JRJoe Rogan22:39

      Yikes.

   5. DSDavid Sinclair22:39

      ... the blood flows between them. Yeah, it's- it's not so pleasant but they- they don't seem to be too badly affected once they learn how to walk in sync.

   6. JRJoe Rogan22:49

      Jesus. Now, uh... (laughs)

   7. DSDavid Sinclair22:52

      (laughs) By the way, to all you listeners, we don't do those experiments in my lab. But, uh, when I say we, I mean-

   8. JRJoe Rogan22:57

      Yes. Scientists.

   9. DSDavid Sinclair22:58

      ... we, scientists.

   10. JRJoe Rogan22:58

       The scientific community as a whole. Um, w- what are your thoughts on, if you have any, about the startups that are actually taking the blood of young people and in- injecting it into the bodies of older folks?

   11. DSDavid Sinclair23:14

       Uh, s- so I don't think there's a scientific reason to say it won't work, and the scientists who are involved are some of my great colleagues, uh, very smart people. Um-

   12. JRJoe Rogan23:22

       Have you ever done it?

   13. DSDavid Sinclair23:23

       No. No, it's a bit extreme for me, but I think it could work.

   14. JRJoe Rogan23:27

       Right.

   15. DSDavid Sinclair23:27

       Uh, it's just a little bit out there for me.

   16. JRJoe Rogan23:30

       A little.

   17. DSDavid Sinclair23:30

       But what- what they're going to do, what they're doing actually is treating people with neurological disorders, um. A lot of these startups, and I- I'm involved in probably 15 startups right now, what we're trying to do is treat diseases of aging, uh, and even rare childhood diseases because you can't treat aging, uh, as a business model. There is no disease called aging yet.

   18. JRJoe Rogan23:50

       Right.

   19. DSDavid Sinclair23:50

       Um, but I... anyway, getting back to the science, I think that it's based on sound science. But the future is- is, I think, a- a better way to go about this is to find what the actual molecules are in the blood and just make those, don't give the whole kit and caboodle.

   20. JRJoe Rogan24:05

       Yeah. And, uh, when you- you've said this twice, you think aging is a disease or maybe perhaps should be treated as a disease or classified?

   21. DSDavid Sinclair24:12

       Oh, I absolutely think aging should be classified as a disease. We should think of it as a disease. I mean, uh, why- why shouldn't we? Everything else that goes on in the body over time that's bad for us is considered a disease. D- do you know why aging isn't considered a disease formally?

   22. JRJoe Rogan24:27

       Because it happens to everybody?

   23. DSDavid Sinclair24:28

       Exactly.

   24. JRJoe Rogan24:29

       Hmm.

   25. DSDavid Sinclair24:30

       That's the only reason. Well, it happens to most people, 90% of people in the developed world, but why is that a reason to say, "Oh, it's natural, we should just deal with it?"... we used to say that about cancer and we used to say that about dying from an infection.

   26. JRJoe Rogan24:41

       When you say it happens to 90% of the people in the developed world, what happens to the other 10? They die?

   27. DSDavid Sinclair24:46

       Hit by a bus, I guess.

   28. JRJoe Rogan24:47

       Oh, okay. I see what you're saying. So they die young?

   29. DSDavid Sinclair24:50

       Yeah.

   30. JRJoe Rogan24:51

       Okay. Just clarifying. Um, uh, yeah, I agree. I mean, it, it's c- I mean, dis-ease. It's a, it's a, it's a problem, right? Aging's a problem. You, I, I saw an old gentleman yesterday and it was painful just to watch this poor guy walk, um, you know, hunched over and just struggling to move at an incredibly slow pace. That seems like a person with a disease.
7. 29:10 – 33:29

   Blue Zones and calorie restriction: Okinawa, portion control, and fasting practicality

   1. JRJoe Rogan29:10

      That's an interesting way of looking at it. Um, what populations as a whole, you know, when you look at the world, um, what, where are the people living the longest and why?

   2. DSDavid Sinclair29:22

      Well, it's debatable. Um, there are these Blue Zones. I think many of your listeners will have heard about those. Um, but there are pockets that have great genes, um, but they also have great diets and lifestyles. And so the, the best one that I'm familiar with is the, uh, island of Okinawa in Japan. And, uh, and by the way, I used to follow the Okinawa diet. Uh, a couple of my good friends wrote a book about it. So I was on tofu and some fish, felt really great, couldn't keep it up. But those people-

   3. JRJoe Rogan29:50

      Why couldn't you keep it up?

   4. DSDavid Sinclair29:51

      Uh, I had kids and our meals turned into pizzas and pasta.

   5. JRJoe Rogan29:55

      Oh. (laughs)

   6. DSDavid Sinclair29:55

      And yeah, unfortunately, but, uh, I'm getting back there now that my kids are teenagers. But, uh, the Okinawans, they, they live, uh, into their 100s, uh, fairly frequently. It's not one in a million. It's, it's more like one in, I think, 100,000 or something. So it's 10 times higher. They, they work, uh, most of their lives. They're physically active. They fast a lot and they have a lot of green leafy vegetables. And that seems to be the secret.

   7. JRJoe Rogan30:21

      And there's a, there were, th- they were selling s- something, it was something about their mineral rich diet. They, remember they were selling, it was like a big thing for a while, coral calcium, and they were using that as an example of why the Okinawans were living so long. Do you remember that kinda-

   8. DSDavid Sinclair30:36

      I do remember it.

   9. JRJoe Rogan30:37

      ... fad?

   10. DSDavid Sinclair30:37

       Yeah. But in scientific circles, we weren't really bothered with it.

   11. JRJoe Rogan30:41

       ... yeah. Like, there's, calcium is calcium, right?

   12. DSDavid Sinclair30:45

       Yeah. I don't, I don't know-

   13. JRJoe Rogan30:46

       I don't know if better-

   14. DSDavid Sinclair30:46

       ... much about it.

   15. JRJoe Rogan30:47

       ... better calcium from coral or something. I, I, I might even be wrong about that.

   16. DSDavid Sinclair30:51

       Yeah.

   17. JRJoe Rogan30:51

       But I just remember, um, reading about the Okinawans and the, the speculation. They eat seaweed as well, right?

   18. DSDavid Sinclair30:59

       They do.

   19. JRJoe Rogan30:59

       Which is very healthy.

   20. DSDavid Sinclair31:00

       Probably the, the best thing that they do is they don't overeat.

   21. JRJoe Rogan31:03

       Hmm.

   22. DSDavid Sinclair31:03

       You know, stop at 70%.

   23. JRJoe Rogan31:06

       Yeah. I'm a glutton. That's my number one problem. I just love to eat.

   24. DSDavid Sinclair31:11

       Yeah. Yeah. Me too. It's a struggle.

   25. JRJoe Rogan31:12

       And I keep going. Once I'm in it, I just wanna just keep f- shoving it in my face. But I've done a good job over the last few years of tapering that off and the intermittent fasting, I think, is probably one of the best things I've ever done in terms of, you know, just maintaining energy levels, maintaining body weight, that kinda stuff.

   26. DSDavid Sinclair31:29

       Yeah. Yeah. You, you look good. So I think that that's one of the best things that people can do. What we've known for 70 or more years actually is if you calorie restrict animals, actually even yeast cells and worms, they live longer.

   27. JRJoe Rogan31:42

       Hmm.

   28. DSDavid Sinclair31:42

       And this is the most robust way to, to prevent cancer, heart disease, Alzheimer's in a mouse. Um, and so the intermittent fasting is just a way of mimicking this calorie-restricted diet. So what, what is calorie restriction? It's reducing what you would, your doctor would recommend for your body, but reducing it back to about 20% to 30%. So it's quite extreme. That's not pleasant. I tried that for a week, gave up. Too hard. But intermittent fasting, like yourself, it, it's doable, it's not always pleasant, but, uh, I think that's the best way to do it. And with the mice, it works just as well, um, as calorie restriction, which is pretty much always being a bit hungry.

   29. JRJoe Rogan32:18

       Now, what other things are you looking at in terms of, um, mitigating stress or, like, what, what other factors are there that, that you have to keep an eye on?

   30. DSDavid Sinclair32:27

       Yeah. Stress is a bad one. Um, I try to, uh, take life in my stride, not get too worried about it, remember what's important. So my heart rate rarely goes up, um, even under really extreme circumstances. Uh, and that, that's about it. I try to, uh, balance my life as best I can. I don't go through airport scanners as much as I can and have X-rays. Uh, these little things.
8. 33:29 – 38:30

   The epigenome theory of aging: ‘scratched DVD’ information loss and DNA breaks

   1. DSDavid Sinclair33:29

      Uh, anyway, so I, I, I used to go through scanners but I try not to. But let me tell you why I think it's so bad. Because scanners are gonna change, uh, what we call the epigenome. Now, a lot of people haven't heard of the epigenome. The genome, everybody knows, it's your DNA, uh, the code of life. The epigenome is what regulates and reads those genes at the right time. Okay? And so we've, we knew about DNA. We know how to read the genome pretty easily. We can do that now on a Mars bar-sized device in a day. Uh, the epigenome's quite diff- different. The epigenome is the, the structure of how the DNA's looped around. If you look at the chromosome, you're not seeing the genome. You're really basically seeing the epigenome. And what w- what I think is causing aging is not that you're losing the DNA structure, you're not having mutations, you're actually changing the epigenome which is the, the reader of the genes. So put another way, uh, compact disc. Okay? Uh, for the young audience, uh, compact discs are little things we used to put music on.

   2. JRJoe Rogan34:35

      (laughs)

   3. DSDavid Sinclair34:35

      Uh, but anyway, these are, these are, uh, digital information of course. And the reason we switched to digital in the first place is that it's very copyable and it doesn't wear out, whereas a, a cassette tape, you know, people our age know that if you try to copy that a thousand times, there's not much left at the end. So the, the compact disc information is the genome. The epigenome is the reader of the CD, that little laser that goes around. And what I think is causing aging is not the loss of the digital information but it's the reader, the analog part and that's like a, a cassette tape that eventually runs out. So what we th- what's going on really is that your cells are losing the ability to read the right genes the way they did when you were 20, and that's basically noise, informational noise that gathers over time. Um, and so what we end up with when we're 80 is a compact disc or a DVD that's scratched so the reader cannot read the right genes the right time and the cells become dysfunctional. Now what we're working on is how do you polish that CD or that DVD to get that information back again, and if you could do that, I think that's really the best way to reset your age. And I, uh, uh, we haven't polished it yet but, uh, we're working on ways to actually reset that genome and actually get back the information that we once had when we were 20.

   4. JRJoe Rogan35:56

      So what is happening to the epigenome when you're going through those scanners?

   5. DSDavid Sinclair35:59

      Well, so what we found is the biggest disruptor of the epigenome is a, a broken chromosome, a DNA break. And I don't know about scanners, that's just a- abundance of caution, but an X-ray will damage your DNA, no question. Um, even going out in the sun will do a bit of that. And we think that the cell's reaction to that break, having to unwrap the, the DNA from its chromatin we call it, and, uh, and then rewrap it is what eventually disrupts the ability to read the right gene at the right place. So DNA damage is essentially a s- a little scratch on, on the DVD and that accumulates over time.

   6. JRJoe Rogan36:37

      So being out in the sun does that? But being out in the sun also is beneficial, your body produces more vitamin D?

   7. DSDavid Sinclair36:44

      Yeah. Well, th- so there's also a theory called antagonistic pleiotropy which is what's good for you when you're young comes back to bite you when you're old.

   8. JRJoe Rogan36:50

      Ah.

   9. DSDavid Sinclair36:51

      So you might look good and feel good and get vitamin D when you're young but the c- accumulation of these scratches on the-... epigenome ends up ... You know, I'm formerly an Australian, originally an Australian. I'm now American and Australian. Uh, I grew up in the Australian sun, and I can tell you that, you know, most Australians look older than they should.

   10. JRJoe Rogan37:10

       No ozone.

   11. DSDavid Sinclair37:12

       Uh, no ozone, and lack of sunscreen in the 1970s.

   12. JRJoe Rogan37:15

       Why do you guys have a hole in the ozone over Australia? What's that all about? What'd you do?

   13. DSDavid Sinclair37:19

       Uh, no, it's what, what did the world do? Chlorofluorocarbons-

   14. JRJoe Rogan37:22

       No, no, no, you guys did it.

   15. DSDavid Sinclair37:23

       Oh, sure.

   16. JRJoe Rogan37:23

       (laughs)

   17. DSDavid Sinclair37:24

       Uh, well, hairspray-

   18. JRJoe Rogan37:26

       B- but why, why does it accumulate over Australia? Is there a theory behind that?

   19. DSDavid Sinclair37:29

       Well, it, it started in Antarctica, and, uh, so ozone will-

   20. JRJoe Rogan37:33

       That'd be convenient. Nobody's up there. Leave it up there.

   21. DSDavid Sinclair37:35

       Yeah, well, unfortunately, you need-

   22. JRJoe Rogan37:36

       Maybe we'd need a big fan, blow it that way.

   23. DSDavid Sinclair37:39

       Yeah. Well, yeah, the, the, the ozone layer, uh, is fairly important, uh, if you don't wanna get singed by UV light.

   24. JRJoe Rogan37:46

       Yeah.

   25. DSDavid Sinclair37:46

       Yeah.

   26. JRJoe Rogan37:47

       Well, that's one of the first things I noticed when I went to Australia, was, uh, there's all these sun cancer warnings, skin cancer warnings everywhere.

   27. DSDavid Sinclair37:54

       Well, a third of Australians get some form of k- skin cancer, so it's-

   28. JRJoe Rogan37:57

       That's crazy.

   29. DSDavid Sinclair37:58

       Yeah. But what's also gonna happen is it'll disrupt your epigenome over time.

   30. JRJoe Rogan38:02

       Mm.
9. 38:30 – 46:10

   Cellular reprogramming and restored vision in mice: glaucoma trial roadmap

   1. JRJoe Rogan38:30

      Hm. So what do you do?

   2. DSDavid Sinclair38:32

      We reprogram them. There are a set of genes that we f- we and others have found, uh, three main ones, that when you put them into a cell or even into a mouse, uh, they become younger again.

   3. JRJoe Rogan38:45

      Whoa. How far do you think you are from implementing this on human beings?

   4. DSDavid Sinclair38:50

      Uh, well, so theoretically, uh-

   5. JRJoe Rogan38:52

      Are you doing it to yourself already?

   6. DSDavid Sinclair38:53

      ... you could, you could do it to yourself.

   7. JRJoe Rogan38:55

      Theoretically.

   8. DSDavid Sinclair38:55

      I would- I wouldn't do that 'cause I'm not crazy.

   9. JRJoe Rogan38:59

      Hm.

   10. DSDavid Sinclair38:59

       We need to figure out the safety. I don't wanna become a giant tumor.

   11. JRJoe Rogan39:02

       Why don't we just use it on bad people?

   12. DSDavid Sinclair39:04

       Uh, yeah, well, that ... No comment.

   13. JRJoe Rogan39:05

       Take people in death row and turn them into 18-year-olds and go, "Whoa."

   14. DSDavid Sinclair39:09

       Yeah. Well, yeah, that, that would be for someone else, uh-

   15. JRJoe Rogan39:13

       Someone else?

   16. DSDavid Sinclair39:14

       Well, hopefully no one would ever do that.

   17. JRJoe Rogan39:16

       Why not?

   18. DSDavid Sinclair39:17

       Well-

   19. JRJoe Rogan39:17

       You're gonna kill them.

   20. DSDavid Sinclair39:18

       ... here's, here's what we're doing. I, I agree with you that we wanna, we wanna see what happens in humans.

   21. JRJoe Rogan39:23

       Yeah.

   22. DSDavid Sinclair39:23

       Uh-

   23. JRJoe Rogan39:23

       I mean, just give them, like, free pizza or something. They're on death row, right? If you're ... They're already murderers.

   24. DSDavid Sinclair39:30

       Do you wanna be the first one?

   25. JRJoe Rogan39:32

       Because, to me, I'm not on death row-

   26. DSDavid Sinclair39:33

       Coming out alive?

   27. JRJoe Rogan39:33

       ... I don't wanna go onto death row. But I'm saying, if you're gonna kill somebody, like, wouldn't it be a good idea to, like, go, "Hey, we'll give you, uh, four hours of TV a day."

   28. DSDavid Sinclair39:42

       Sure.

   29. JRJoe Rogan39:42

       "We wanna ... We'll shoot you up with some stuff that's gonna make you younger." If I was on death row, I'd go, "Do it. See what's up."

   30. DSDavid Sinclair39:49

       Well-
10. 46:10 – 1:13:06

    Measuring biological age: blood tracking, InsideTracker, and the DNA methylation clock

    1. DSDavid Sinclair46:10

       Good question. How does anybody? Um, so we live in an age that is still fairly primitive. This is why I like the future. Um, these days, we go to the doctor, most of us go to the doctor for annual physical, which is ludicrous. The idea that, uh, your doctor will take a, hopefully a blood test, uh, a prostate exam once a year. That's kind of crazy. What happens if you've got a tumor that developed the day you leave the doctor's office? So the future-

    2. JRJoe Rogan46:34

       Hmm.

    3. DSDavid Sinclair46:34

       ... and actually partially for those who are on the cutting edge can be done right now, it's monitoring your body, uh, in various ways, genetically, epigenetically. We can measure those scratches right now. And also, uh, with blood tests. You can also, uh, have companies tell you, uh, if you're out of range, if you're not optimized, and how to get it back in order. So that's what I do.

    4. JRJoe Rogan46:57

       So how often do you monitor your blood?

    5. DSDavid Sinclair46:59

       Uh, probably every few months I have a blood test, uh, from a company that tells me what I need to correct.

    6. JRJoe Rogan47:06

       And how extensive is this, is this blood test? Like is it a standard one that a normal person can get, or do you have to have prescription to get this or-

    7. DSDavid Sinclair47:12

       Uh, no. You can go online and get it. Uh, it's about, I think, 40 parameters they measure, some that are not standard that your doctor wouldn't do. Some are pretty standard. Um, but what's nice is it's, it's a tracking system. It's called InsideTracker, and they, you can see over time if things are going up. And even if they're not out of range yet, you can see if they're headed that direction-

    8. JRJoe Rogan47:30

       Hmm.

    9. DSDavid Sinclair47:30

       ... and correct it before it's too late. So that's why, one of the reasons I'm on metformin, my blood glucose was going up and up and up, which predicts lower life. And so metformin got it back down to where it was optimal again.

    10. JRJoe Rogan47:43

        So that's one of the things that metformin does, is it lowers your blood glucose?

    11. DSDavid Sinclair47:46

        That's what it's prescribed for, for diabetics.

    12. JRJoe Rogan47:48

        Hmm. Now does that have any effect on your energy levels?

    13. DSDavid Sinclair47:52

        Uh, I don't think so. I haven't noticed that.

    14. JRJoe Rogan47:56

        D- Hmm. Um, where you would notice it is during rigorous exercise.

    15. DSDavid Sinclair48:00

        That makes sense.

    16. JRJoe Rogan48:01

        Do you feel it? Do you-

    17. DSDavid Sinclair48:03

        Uh, well, so I take metformin at night.

    18. JRJoe Rogan48:05

        Mm-hmm.

    19. DSDavid Sinclair48:06

        Um, so that may be probably the best thing.

    20. JRJoe Rogan48:09

        Right. So when you're sleeping, it's having its effect and it's run its course, by the time you wake up, you bleed?

    21. DSDavid Sinclair48:13

        Yeah.

    22. JRJoe Rogan48:14

        Hmm. Um, now when you, you are exercising, are you exercising fasted or do you take a certain amount of carbohydrates before you do any kind of physical exercise?

    23. DSDavid Sinclair48:24

        Uh, so I start at the gym, uh, 2:00, 2:00 PM on a Sunday, and I'll have s- a salad wrap or something like that, so I'm not feeling hungry during it and I won't pass out.

    24. JRJoe Rogan48:34

        Huh. And, um, so I, I understand that you're getting these blood tests, but do you have a trainer? Do you, do you set a workout or do you structure it?

    25. DSDavid Sinclair48:45

        Uh, I do now. Just, uh, recently got a trainer. Um, it's a great thing to do with your son, um, father-son time. So yeah, that, that we have an hour of trainer, and then we, we also do a bit of boxing, um, in the evening or something.

    26. JRJoe Rogan48:58

        Beating your kid up? You're beating your son up? (laughs)

    27. DSDavid Sinclair49:00

        Yeah, it's fun. It's legal, I think. Uh, go to the sauna, and then, uh, that's just the best way to spend a day.

    28. JRJoe Rogan49:07

        That is a nice way to spend a day. So, um, are, you, how many days a week are you doing this? Do you give yourself days off? Do you-

    29. DSDavid Sinclair49:14

        Yeah.

    30. JRJoe Rogan49:14

        ... schedule that?
11. 1:09:33 – 1:29:48

    CRISPR and designer babies: ethics, secrecy, and international competition

    1. JRJoe Rogan1:09:33

       Hmm. Now, um, uh, what about CRISPR and what do you think, uh, is going to come out of that in terms of, like, real world application for an adult? I mean, what ... If people don't know what CRISPR is, please explain it in, in, in the layman's terms.

    2. DSDavid Sinclair1:09:51

       Uh, yeah. So CRISPR is a, a term, um, actually it was invented in, in my department partly, so I know it pretty well. It's, uh, bac- bacteria have an immune system that cuts invaders, it cuts their DNA. Uh, and what we've done now, as scientists, we've now utilized that, uh, system, take it outta the bacterium, and we use it to create designer mutations, designer gene changes in animals and also in humans. So it's a bacterial immune system that corrects genes. And we use it all the time now. It's, um, it's, it's actually, what's interesting about it is we've been able to mutate genes for many years, but this is dial up a gene mutation. You can choose exactly where you wanna make it. And, uh, so I think many of your listeners will know that recently, uh, late last year, a Chinese researcher in our field came out and said he's engineered a couple of twin girls with CRISPR to be resistant to HIV, the AIDS virus.

    3. JRJoe Rogan1:10:47

       Wow. Um, if they're telling you that, you gotta think they're doing some stuff they're not telling you about, right?

    4. DSDavid Sinclair1:10:54

       Well, yeah.

    5. JRJoe Rogan1:10:55

       They gotta have some kids with giant heads and-

    6. DSDavid Sinclair1:10:57

       Well, it's coming.

    7. JRJoe Rogan1:10:58

       ... see through walls-

    8. DSDavid Sinclair1:10:59

       Yeah.

    9. JRJoe Rogan1:10:59

       ... read minds.

    10. DSDavid Sinclair1:11:00

        Well, yeah, if you start to see people, uh, that are 90 and, uh, and they're still as young as 20, you know something's going on.

    11. JRJoe Rogan1:11:08

        Yeah, that's the weird one, right? If you can ... Y- you'd go, "Hey, what are you doing?" "Nothing. Just eating healthy, looking good. Take care. Bye." (laughs)

    12. DSDavid Sinclair1:11:16

        Tha- that's right.

    13. JRJoe Rogan1:11:16

        They're not gonna tell you. (laughs)

    14. DSDavid Sinclair1:11:18

        Yeah, yeah. Well, so consider this, that, that, so the chance of getting HIV in China is one in 1000. So that doctor was seemingly ... He thought he was ethical protecting the babies from something that's-

    15. JRJoe Rogan1:11:29

        Hmm.

    16. DSDavid Sinclair1:11:29

        ... I would say really rare.

    17. JRJoe Rogan1:11:30

        Right.

    18. DSDavid Sinclair1:11:31

        Whereas if you really want to do something helpful to those kids, and we agreed it was, it was something you should do, why not make them resistant to heart disease or to cancer?

    19. JRJoe Rogan1:11:40

        Right.

    20. DSDavid Sinclair1:11:40

        We can do that. It was weird that he chose HIV as the first test.

    21. JRJoe Rogan1:11:44

        Why do you think they did that?

    22. DSDavid Sinclair1:11:46

        Um, I think because the, it was a very, um, well-understood mutation that would, if you just destroyed the gene, it would work. Whereas with these other diseases, you have to be much more precise. But the reason that we scientists got really upset was that he did it in secrecy and then just la- launched it on the world.

    23. JRJoe Rogan1:12:04

        Hmm.

    24. DSDavid Sinclair1:12:04

        And, and that kind of thing, because the, it's a fine line in ethics, you wanna be doing that with total transparency.

    25. JRJoe Rogan1:12:11

        Right.

    26. DSDavid Sinclair1:12:11

        And in ... I think he was hoping to become, um, win a Nobel Prize or be, uh, a star, and it, it backfired on him because he, he just did it in secrecy.

    27. JRJoe Rogan1:12:21

        It backfired in the scientific communities?

    28. DSDavid Sinclair1:12:23

        Absolutely. In the, in the real world, in the media, I was shocked how little discussion there was. If this news came out in the 2000s during the Bush era, it would, there would've been panels, investigations, it would've been in the news for months, but it wasn't. People went, "Uh, what's next on Twitter?"

    29. JRJoe Rogan1:12:39

        Do you think it's just 'cause the news cycle is so insane?

    30. DSDavid Sinclair1:12:41

        I do.

Episode duration: 2:21:04