Joe Rogan Experience #1349 - David Sinclair

1. 0:00 – 2:04

   Metformin/DHEA/Growth Hormone study and the promise of age reversal

   1. JRJoe Rogan0:00

      (clears throat) David Sinclair, Lifespan: Why We Age & Why We Don't Have To. I'm so happy there are people like you out there, 'cause I don't wanna age. I'm aging, clearly, but, uh, I'm not interested in it. I don't like it.

   2. DSDavid Sinclair0:17

      Yeah. Well, I don't know anybody who does, uh, Joe Rogan. Thanks for having me back on.

   3. JRJoe Rogan0:20

      Thanks for coming back. The first one was a, a smash hit, man. People loved it. Uh, all my friends were very excited. But, uh, I had a question for you right off the bat, um, regarding Metformin. There was actually an article, I'm sure you saw it, recently, um, like within the last couple of days, that was going around through all the mainstream papers. It was, uh, talking about how for w- the use of Metformin, uh, DHEA, and w- was there something else as well that was taking two years-

   4. DSDavid Sinclair0:49

      Human growth hormone.

   5. JRJoe Rogan0:50

      ... human growth hormone, taking two years, two biological years off of people's lives in terms of their, their age, which are natural eight, which are actual ... I'm 52, it would make me 50.

   6. DSDavid Sinclair1:00

      Right. Even 49.5, according to the study.

   7. JRJoe Rogan1:02

      Ooh.

   8. DSDavid Sinclair1:02

      Yeah.

   9. JRJoe Rogan1:02

      That's what I'm looking for.

   10. DSDavid Sinclair1:04

       Yeah, that was a-

   11. JRJoe Rogan1:04

       Get back to the fours.

   12. DSDavid Sinclair1:05

       ... that was a good study. Uh, it, you know, it's only nine people, so we have to repeat this. Um-

   13. JRJoe Rogan1:10

       Were they studs? Did you get like nine super athletes or did you get like schmoes that don't exercise?

   14. DSDavid Sinclair1:15

       Uh, I, as far as I know, these were just, uh, regular-

   15. JRJoe Rogan1:18

       Schmoes?

   16. DSDavid Sinclair1:19

       ... schmoes, yeah.

   17. JRJoe Rogan1:20

       (laughs)

   18. DSDavid Sinclair1:20

       Which is good news for schmoes like me.

   19. JRJoe Rogan1:22

       Yes. Good news. Yeah. Well, I mean, that's what you want. You don't want like ... Some people just respond better. They're, they have super bodies, you know?

   20. DSDavid Sinclair1:29

       Well, the gre- great thing about that, uh, study is first of all, I, I was with the first, uh, the main author on that paper, uh, while it came out. I was over in Israel, uh, as part of my journey up the, the great rift of Africa, ended up in Israel. Anyway, the guy there, uh, Steve Horvath is his name, uh, he and I and a couple of other guys are trying to figure out, uh, not just why we age, why we don't have to, but is aging, uh, truly reversible? And that's what this study suggests is that it's not just about slowing down aging, but one day we could be 80, but biologically 30.

2. 2:04 – 4:59

   The Horvath epigenetic clock: how “biological age” is measured

   1. JRJoe Rogan2:04

      Now, when we're talking about the biological age, how is that measured? Is this measured by the length of the telomeres? Is this measured by physical performance? Is it measured by a combination of these factors?

   2. DSDavid Sinclair2:17

      It's none of that.

   3. JRJoe Rogan2:18

      None of that?

   4. DSDavid Sinclair2:18

      It's something brand new.

   5. JRJoe Rogan2:19

      Ooh.

   6. DSDavid Sinclair2:19

      Most people don't know about it. So it's called the Horvath Clock. And what Horvath and others have discovered is that if you read the DNA and you don't just look at the letters A, C, T, G, if you look at what's on the letter C, cytosine it's called, there are chemical modifications. And those chemicals change as we get older in very linear and predictable ways. If you use a computer, AI, you can say, if I took your blood sample right now, I could read your DNA, look at those chemical groups on the Cs, and I could say you are, okay, you're 52, you might be 46 according to that clock. Uh, and also I could predict when you're gonna die.

   7. JRJoe Rogan2:58

      Whoa.

   8. DSDavid Sinclair2:59

      Scary thought, right?

   9. JRJoe Rogan3:00

      Yeah, like a fortune teller.

   10. DSDavid Sinclair3:02

       Yeah. But the good news is, well, now that we know what's not just, uh, measuring aging, we actually think that clock is part of the aging process, we're learning how to reverse it too.

   11. JRJoe Rogan3:11

       Hmm. Now is this just one modality, this, this combination of gr- growth hormone? Is this one w- way of going about it? Are there other ways of going about it? Growth hormone, DHEA, Metformin, is there anything else?

   12. DSDavid Sinclair3:27

       Well, that's the first that's ever been shown to really-

   13. JRJoe Rogan3:29

       So it's just those three things?

   14. DSDavid Sinclair3:30

       ... reverse. But I'm sure there's gonna be many more discovered. We've only had this Horvath Clock over the last few years in humans, uh, being used widely. Uh, but I think as we use this clock, uh, we're gonna figure out that a whole bunch of stuff that we do and things that we can do and combine will not just slow aging, but reverse it. And not just by two and a half years, eventually, and some of the technology that I talk about in my book, we think could turn the clock back by a decade or more.

   15. JRJoe Rogan3:57

       Whoa. Now what things are you talking about that could possibly turn it back a decade or more?

   16. DSDavid Sinclair4:02

       Well, so the-

   17. JRJoe Rogan4:03

       And who do I have to blow?

   18. NANarrator4:05

       (laughs)

   19. DSDavid Sinclair4:05

       Sorry. (laughs)

   20. JRJoe Rogan4:06

       Uh, yeah, you can blow me, but-

   21. DSDavid Sinclair4:10

       (laughs)

   22. NANarrator4:10

       (laughs)

   23. DSDavid Sinclair4:10

       Yeah, you may have to do it a few times.

   24. JRJoe Rogan4:12

       (laughs)

   25. DSDavid Sinclair4:13

       But, uh, the, uh, the amazing thing about, uh, where we are now today with aging, um, and we're right on the cutting edge, so it's great to be able to share this with your listeners, is this clock, it's, uh, changes on the DNA, right? What I'm saying, uh, uh, in my theory of, uh, of aging is that it's not the DNA that we lose. That's the old theory. You know, the old idea that antioxidants hurt the DNA.

   26. JRJoe Rogan4:37

       Yes.

   27. DSDavid Sinclair4:38

       Just throw that out for a while, uh, maybe forever. What I think is going on is it's the DNA is getting modified and the cell can't read the DNA the way it used to. Okay? That's really important. And so the clock is not just a clock, it's not a clock on the wall, it's also if you move the hands of the clock, time changes. That's what I think is going on.

3. 4:59 – 6:50

   Antioxidants disappoint; resveratrol, sirtuins, and how to take it

   1. JRJoe Rogan4:59

      Could we pause right here for a moment and explain what you were saying about antioxidants?

   2. DSDavid Sinclair5:04

      Well, antioxidants have been the biggest disappointment, uh, in the aging field. Um, doesn't stop, you know, 40 million people every day buying drinks with antioxidants in them. But antioxidants have, with very few exceptions, failed to extend the lifespan of any organism.

   3. JRJoe Rogan5:20

      But you are a proponent of resveratrol, at least you used to be. Are you still?

   4. DSDavid Sinclair5:24

      I still take it. Um, and we still study it in my lab. But what's ... You brought this up, it's really important. Resveratrol was originally thought to be an antioxidant, and it is a mild antioxidant, but the way it really works, we know this is a fact from my lab, is that it's stimulating the body's defenses against aging and disease because it's, it's binding to these enzymes that we work on called sirtuins, and these are the defenders of the body.

   5. JRJoe Rogan5:51

      And you were saying the ... If I remember correctly, you take resveratrol, you take a powdered form, actually bought exactly what you take, and you mix it with yogurt in the morning. Is that, is that how you do it?

   6. DSDavid Sinclair6:01

      Yep. A teaspoon.

   7. JRJoe Rogan6:01

      What, what's the dose that you take?

   8. DSDavid Sinclair6:03

      Well, it probably comes out to about a gram in the morning.

   9. JRJoe Rogan6:06

      A gram?

   10. DSDavid Sinclair6:07

       Yeah.

   11. JRJoe Rogan6:07

       Okay. So if someone's taking capsules.

   12. DSDavid Sinclair6:11

       Well, it depends. If they're c- probably capsules of 250 milligrams, that'd be four in the morning.

   13. JRJoe Rogan6:16

       Okay. So you take four?

   14. DSDavid Sinclair6:16

       Yeah. You know, I'm still alive, so that's... it's a good sign.

   15. JRJoe Rogan6:18

       Right. You look good.

   16. DSDavid Sinclair6:19

       Oh, thank you.

   17. JRJoe Rogan6:20

       Do you, um... is it important to take it with fats? Is that why you take it with yogurt?

   18. DSDavid Sinclair6:26

       Yeah. Yeah. Either high protein, which is, uh, s- you know, a Greek yogurt suffices, or fat. But water, it'll... it's like brick dust, it won't dissolve and it won't get absorbed.

   19. JRJoe Rogan6:37

       Okay. So would a, a glass of whole milk, maybe, would be okay?

   20. DSDavid Sinclair6:39

       Yeah. That's great.

   21. JRJoe Rogan6:40

       But it has to have something to bind to, is that the deal?

   22. DSDavid Sinclair6:42

       For sure. Yeah. In, in our studies, in humans and in mice, if we didn't give them high fat food, it barely got in. There was five-fold le- less.

4. 6:50 – 8:54

   NAD biology: CD38, NMN/NR, and combining interventions

   1. JRJoe Rogan6:50

      Now, this study of metformin, DHEA, and human growth hormone does not include NMN.

   2. DSDavid Sinclair6:59

      Right.

   3. JRJoe Rogan7:00

      So... but NMN is also effective.

   4. DSDavid Sinclair7:03

      Ah. Well, let's delve in a little bit.

   5. JRJoe Rogan7:05

      Please.

   6. DSDavid Sinclair7:05

      If you read the paper, uh, and I, I have, uh, it turns out one of the effects of this treatment was the reduction in the levels of a protein called CD38. CD38 resides on immune cells, and it goes up as we get older. And what they found, one of the biggest effects of the treatment was the levels of this CD38 protein went down. So what is the... CD38? This is the main enzyme in our bodies that degrades NAD. NAD is required for these sirtuin defenders to work. So one possibility is that, uh... and I'm sure it's complicated, but one way this could be working is by allowing your body to make NAD and store it, rather than degrading it as we get older.

   7. JRJoe Rogan7:48

      Interesting. So would supplementing with NMN, which is a form of NAD, correct?

   8. DSDavid Sinclair7:56

      A precursor, yeah.

   9. JRJoe Rogan7:57

      Precursor. Would that, uh, enhance the effects, do you believe? Like, if they tried to do a new study?

   10. DSDavid Sinclair8:04

       It could.

   11. JRJoe Rogan8:05

       Could.

   12. DSDavid Sinclair8:05

       It could.

   13. JRJoe Rogan8:06

       Potentially.

   14. DSDavid Sinclair8:06

       Um, each of these patients cost $10,000 for the treatment, so it's, it's not easy to do these studies.

   15. JRJoe Rogan8:11

       $10,000 for the entirety of the treatment? And the treatment lasts how long?

   16. DSDavid Sinclair8:17

       Um, I don't remember how long they treated the patients for. Uh, but I do know, uh, that it wasn't cheap. That's why they only did nine, 'cause I... at first, I said to my friend Steve Horvath, "Nine patients? Are you kidding me? Why didn't you do 50?" And they went, "Well, we didn't have the money. That's the... that's the problem."

   17. JRJoe Rogan8:33

       Hm.

   18. DSDavid Sinclair8:34

       Anyway, my point really is that we need to test a lot of different combinations. Include NMN, include, uh... there's one called rapamycin which is a little bit more risky and toxic, but there are better molecules in development. The question is, what is the best combination? And do you use it with exercise and fasting, um, or is it bad to combine them all together? We don't know yet.

5. 8:54 – 12:59

   Metformin and exercise: performance tradeoffs and “pulsing” strategy

   1. JRJoe Rogan8:54

      That's a good question, too, that I wanted to ask you, because one of the things that came out of the podcast was input from some other people that I know that are nutrition experts and performance experts that were skeptical about metformin. And they were saying that metformin, although it may have, uh, an anti-aging effect, it actually decreases physical performance in athletes.

   2. DSDavid Sinclair9:14

      Well, that... there is a study that shows that. Uh, and resveratrol too, actually, uh-

   3. JRJoe Rogan9:18

      Really?

   4. DSDavid Sinclair9:19

      ... can, can prevent the, the great gains from hard exercise. So here's the solution, uh, that I think, uh, is worth trying. A solution. And that is, uh, a theme that, that I have in my book and in my, uh, my research, and that is, we don't wanna be doing everything every day, necessarily. We wanna pulse it. We wanna shock the body and let it recover. We know that you can't just exercise. I mean, some people who've been on this show run 100 miles every, every weekend. But generally, you wanna hit it hard and let it recover, hit it hard and let it recover. So what I am planning to do, and actually have started doing, is on days that I'm exercising and recovering, I don't take metformin, and then when I'm just sitting around or on a plane, I do. And that way, I think that my body can have the best of both worlds.

   5. JRJoe Rogan10:01

      So when you are not exercising and you take it, you feel like it doesn't have a hit when you are exercising and not taking it? So it... somehow or another, whatever performance hit it has, it's temporary?

   6. DSDavid Sinclair10:15

      Yeah. Right. So while-

   7. JRJoe Rogan10:17

      This is all just theoretical.

   8. DSDavid Sinclair10:18

      It, it, it is. We're right on the cutting edge of human knowledge. We don't actually know what the best thing is. But my, my best guess is that we want to allow the body to recover, so I don't take metformin on those days, rather than taking metformin every day like a diabetic would.

   9. JRJoe Rogan10:32

      Mm-hmm. Now, what are... what is the... what's the hit? Like, what is happening? What's the mechanism behind the performance hit from taking metformin?

   10. DSDavid Sinclair10:40

       Oh. We don't know.

   11. JRJoe Rogan10:41

       We don't know.

   12. DSDavid Sinclair10:41

       But I'll... I can tell you the best, uh, explanation that I can give you. So metformin is a derivate of a plant molecule, the French lilac. So it's, it's not a crazy molecule, it's pretty natural. But what it does is many things in the body. Scientists will quite annoyingly argue about it for, for... they have for the la- past 40 years. Um, so there's no correct answer. But what I think is going on is that metformin is interfering with the mitochondrial... mitochondria in the cell. Mitochondria are the... we call them the battery packs. They're basically making chemical energy. Without that chemical energy, we'd be dead in about 20 seconds. So we need that for life. So metformin interrupts that energy production in the mitochondria. Uh, but you need the mitochondria to amplify after you've exercised. So they're, they're antagonizing each other. So why does metformin work? By inhibiting the mitochondria, the body gets a signal that it doesn't have enough chemical energy, it's not making enough. So it expands the number of mitochondria. These are ancient remnants of bacteria that entered our cells. And we have less if we sit around and... like we are now, and we have more if we exercise. And metformin, by telling the body, "Shit, we're running out of energy," the body responds and makes more mitochondria, just like exercise does.

   13. JRJoe Rogan11:55

       Hm.

   14. DSDavid Sinclair11:55

       But I think if you're taking m- um, metformin and exercising, that inhibition is preventing the benefits, somehow, of what you get with exercise.

   15. JRJoe Rogan12:04

       Perhe- preventing it, how so? Like, what, what did the study... or what studies have been done, and what did they reveal?

   16. DSDavid Sinclair12:10

       Uh, I don't remember the precise details of the study. It was, it was giving metformin every day to people who were, uh, in a controlled exercise, I think it was treadmill, um, a few times a week. Uh, but then what they measured was the mitochondrial benefit. Now that ... Uh, and I think they measured a bit of strength and endurance.

   17. JRJoe Rogan12:28

       It's so confusing if there's a mitoch- mitochondrial benefit but a performance hit.

   18. DSDavid Sinclair12:33

       Well, no, they actually ... Metformin prevented the mitochondria from amplifying up.

   19. JRJoe Rogan12:38

       Oh.

   20. DSDavid Sinclair12:39

       Right? So there, it must be, uh, interfering with the signal that you get from exercise, whatever that is. We don't know exactly what that is.

   21. JRJoe Rogan12:49

       So you'd really have to be some sort of a guinea pig to try to fuck with this stuff, to go back and forth from taking it and exercising, not taking it-

   22. DSDavid Sinclair12:57

       Yeah. I'm, I'm-

   23. JRJoe Rogan12:57

       ... and exercising.

   24. DSDavid Sinclair12:58

       I'm one of those guinea pigs.

6. 12:59 – 17:59

   Heat/cold exposure, hormesis, alcohol, and Sinclair’s travel/workout reality

   1. JRJoe Rogan12:59

      Yeah. And what do you, uh ... No disrespect, but how hard are you working out?

   2. DSDavid Sinclair13:05

      Not enough. Not enough.

   3. JRJoe Rogan13:06

      Yeah. That's what I'm saying.

   4. DSDavid Sinclair13:07

      I, I spend three hours a week in the gym. Uh, nevermind.

   5. JRJoe Rogan13:10

      That's not bad. That's-

   6. DSDavid Sinclair13:11

      It's all in one day.

   7. JRJoe Rogan13:12

      That's mainten- Oh, one day?

   8. DSDavid Sinclair13:13

      Yeah.

   9. JRJoe Rogan13:13

      Really? One day, three hours?

   10. DSDavid Sinclair13:16

       Yeah. That's it.

   11. JRJoe Rogan13:16

       That's ridiculous.

   12. DSDavid Sinclair13:17

       It is.

   13. JRJoe Rogan13:17

       Why are you doing it that way?

   14. DSDavid Sinclair13:18

       'Cause I'm smart.

   15. JRJoe Rogan13:18

       But you're so smart. (laughs) That drives me crazy when smart people do dumb shit. Like I had Peter Hotez on the podcast, who's a, a brilliant man, and from the University of Texas. He's a, a researcher in, uh, tropical diseases and he's obsessed with diseases and the importance of vaccination, all these different things. Then he's talking about how his, his diet is terrible. He eats junk food. He's constantly eating Jack in the Box and shit. I'm like, "What the fuck, man?"

   16. DSDavid Sinclair13:44

       Yeah. That's nuts.

   17. JRJoe Rogan13:44

       You're so smart and you're a guy who works on diseases. What's the number one cause of diseases?

   18. DSDavid Sinclair13:50

       Oh, yeah. I don't, I don't get that. Some of my colleagues-

   19. JRJoe Rogan13:52

       Poor diet.

   20. DSDavid Sinclair13:52

       ... eat the worst food and they study longevity.

   21. JRJoe Rogan13:54

       Crazy. It's crazy. It's like they can't help their impulses. It's like there's so many people like that, that are obsessed with s- various aspects of health or performance, but they just, they just can't get it together.

   22. DSDavid Sinclair14:08

       Well, I would work out more if I had time. I'm usually working 'til midnight, and after that, I'm not really keen to go to the gym.

   23. JRJoe Rogan14:13

       Yes, you do have an excuse. You have a crazy work schedule. You do have an excuse.

   24. DSDavid Sinclair14:17

       Yeah. Well, I, I'm on planes a fair bit, so I try to exercise on the plane. It's pretty hard, and-

   25. JRJoe Rogan14:21

       Do you really? What do you do?

   26. DSDavid Sinclair14:22

       ... in the bathroom ... Um, I stretch.

   27. JRJoe Rogan14:24

       You go to the bathroom and do squats?

   28. DSDavid Sinclair14:25

       (laughs)

   29. JRJoe Rogan14:26

       So nobody thinks you're crazy?

   30. DSDavid Sinclair14:28

       Yeah.
7. 17:59 – 34:56

   Africa origins journey: predators, tribes, and the “natural vs unnatural” debate

   1. DSDavid Sinclair17:59

      Right, right. Well, uh, I was, uh, in Africa recently, and, uh, I gotta tell you, one of the ... When you, when you see a wildebeest get attacked and, and chewed on for 45 minutes by a crocodile-... uh, nothing better than, uh, going back to the camp and having a beer to, to calm down.

   2. JRJoe Rogan18:16

      (laughs)

   3. DSDavid Sinclair18:16

      So I did a lot of that.

   4. JRJoe Rogan18:17

      So when you were on safari, um, how did you ... When, when ... Are you in one of those open Jeep deals?

   5. DSDavid Sinclair18:24

      Uh, yeah, a lot of that. We did also some hiking. We had Maasai, uh, leaders that would go out and ... With a federal, uh, officer with a gun to protect us.

   6. JRJoe Rogan18:32

      Oh, Christ.

   7. DSDavid Sinclair18:33

      Oh, it was fun. It's so much ... It's so different than being in a Jeep, to walk among the cats out there.

   8. JRJoe Rogan18:37

      Oh, yeah, man.

   9. DSDavid Sinclair18:38

      You gotta do that.

   10. JRJoe Rogan18:38

       For sure. You're almost dead. Yeah. It's ... Like, you're right there.

   11. DSDavid Sinclair18:42

       But you feel like you're alive. You know how ... You get the feeling of what it was like to be an early human.

   12. JRJoe Rogan18:46

       I've never encountered anything other than bears in the woods that are terrifying. I've never seen a mountain lion, uh, while, like, hunting. I've only seen two mountain lions ever. One was from my back porch in Colorado, and one was in the street in, uh, Santa Barbara. I was driving and I saw one run across the street.

   13. DSDavid Sinclair19:04

       Right.

   14. JRJoe Rogan19:04

       And I didn't realize it was a mountain lion until I saw the tail. I was like, "Oh, shit." I thought it was a coyote or something, then I saw that long tail. Um, but while hunting, I've ... The only thing I've ever seen is a grizzly bear. I saw a grizzly bear once. I've seen black bears. Black bears are unnerving. Grizzly bears are terrifying.

   15. DSDavid Sinclair19:22

       Right.

   16. JRJoe Rogan19:23

       They look at you like this.

   17. DSDavid Sinclair19:24

       You could shoot at them and they'll still come.

   18. JRJoe Rogan19:25

       They just look right through you. They look like, "Am I eating you? What's going on with you?"

   19. DSDavid Sinclair19:28

       (laughs)

   20. JRJoe Rogan19:28

       "Am I gonna eat you?" Like, they, they're trying ... Black bears are like, "Uh, should I get out of here? Should I run? Am I the boss or are you the boss?" Like, they're not sure. Grizzly bears are fucking sure they're the boss. They're just trying to figure out whether or not they should eat you.

   21. DSDavid Sinclair19:42

       Right. And actually, uh, one of the things you realize when you're amongst these animals, it's a huge privilege for us to go for a walk without getting eaten.

   22. JRJoe Rogan19:49

       Yes. Yeah. We don't think about it that way because we're so used to being in parks and, "Oh, I'm out in nature." The fuck you are. You're not really in nature.

   23. DSDavid Sinclair19:57

       Yeah.

   24. JRJoe Rogan19:57

       You're in some weird sort of nature preserve that we've sort of set up inside cities.

   25. DSDavid Sinclair20:02

       Right. Right.

   26. JRJoe Rogan20:02

       S-

   27. DSDavid Sinclair20:02

       And people ask me about my work, "Oh, isn't what you're doing unnatural?" Fuck natural.

   28. JRJoe Rogan20:07

       (laughs) It's so silly.

   29. DSDavid Sinclair20:08

       What about our world is natural anyway?

   30. JRJoe Rogan20:09

       Well, brushing your teeth isn't natural either, stupid.
8. 34:56 – 48:38

   Religion, origin stories, and human behavior from Jerusalem to Kyrgyzstan

   1. JRJoe Rogan34:56

      That's exciting. Wow, that is so cool. So, what was the most unusual thing?

   2. DSDavid Sinclair35:03

      Besides Jerusalem?

   3. JRJoe Rogan35:04

      Is that the most unusual thing?

   4. DSDavid Sinclair35:06

      Oh, that- that's the most insane thing, where all the religions are on top of each other, touching rocks and blessing the spring and-

   5. JRJoe Rogan35:11

      (sighs)

   6. DSDavid Sinclair35:12

      ... humans are crazy.

   7. JRJoe Rogan35:14

      (laughs)

   8. DSDavid Sinclair35:14

      They'll worship anything. Uh-

   9. JRJoe Rogan35:15

      Well, I'm sure you've seen ... Uh, I was in Germany once and, uh, I was there for UFC and I was flipping through the channels of the television and there was, uh, this live feed from Mecca. And, uh, this was pre-Instagram. I was not on Instagram. I definitely would've... 'Cause I watched it for hours. I just sat there in my room drinking a cocktail with my feet up watching this- these people circle around this... What is that, uh, square-shaped thing in the center of Mecca?

   10. DSDavid Sinclair35:47

       Yeah, I forget. It was a-

   11. JRJoe Rogan35:48

       It was a religious object-

   12. DSDavid Sinclair35:49

       Right.

   13. JRJoe Rogan35:49

       ... that I believe, I think says something to do with an asteroid. Like, there's a piece of some ... Find out if that makes sense. This is important to people. But they, uh, the- the- watching people circle. They're all wearing the religious garb, this Islamic garb that they have to wear. And they're all circling around this thing, like, for hours and hours and hours. And I'm like, it's oddly appealing. Like, part of you wants to go, "I recognize that there's gotta be a very strong sense of unity and community in everybody-"... agreeing that we are all going to treat this, this is a sacred object, this is a sacred place. We're gonna wear sacred clothes and we're all gonna follow this, this path. And this, and we're all gonna be together in this.

   14. DSDavid Sinclair36:38

       Mm-hmm.

   15. JRJoe Rogan36:38

       Like, this, like, super reinforced sense of community that's actually ordained by God Himself.

   16. DSDavid Sinclair36:43

       Yeah. Well, we all need that feeling. For-

   17. JRJoe Rogan36:45

       Yeah.

   18. DSDavid Sinclair36:45

       ... for me, it's science and the fossils that, that I and my colleagues believe were the origins.

   19. JRJoe Rogan36:50

       Yeah.

   20. DSDavid Sinclair36:50

       Everyone needs an origin story.

   21. JRJoe Rogan36:52

       Here it is. Uh, how would you say that? Ka-

   22. DSDavid Sinclair36:55

       Kaaba.

   23. JRJoe Rogan36:56

       Kaaba? Kaaba. It's built around a sacred black stone, a meteorite that Muslims believe was placed by Abraham and Ismail, Ishmael, in the corner of the Kaaba, a symbol of God's covenant with Abraham and Ishmael and, by extension, with the Muslim community itself. Hmm, okay. Yeah, that-

   24. DSDavid Sinclair37:15

       There's-

   25. JRJoe Rogan37:16

       So it is, it is actually a meteorite, which how, how incredible, right? Like, a little bit of science and a little bit of religion all wrapped up together. There's a discovery. So this, this is what it looks like. So you're watching this. Um, the channel that I was watching in Germany, again, this is probably, like, more than 10 years ago, 12 years ago, perhaps. And watching this circle around this, like, religious spot was very, very captivating.

   26. DSDavid Sinclair37:44

       Yeah, the one that I remember, uh, most from, I think it was Jerusalem, yeah, uh, was people touching the stone where the crucifix was thought to be. And they were-

   27. JRJoe Rogan37:52

       Hmm.

   28. DSDavid Sinclair37:52

       ... lined up for hours to just touch it for a, a few seconds. Uh, meanwhile, you know, the origin of humans, the fossils, there's maybe two or three people hanging out. No one really cares. Admittedly, it is out of the way. It's not in the middle of, uh, the Middle East. But still, it, it struck me that humans are more focused on these icons of religion rather than-

   29. JRJoe Rogan38:12

       Yeah.

   30. DSDavid Sinclair38:12

       ... where I believe we really came from.
9. 48:38 – 1:10:17

   Longevity limits, centenarians, and Sinclair’s father as a case study

   1. DSDavid Sinclair48:38

      ... to do that. We'll continue to evolve. And one of the ex- the, the reasons that I wanted to see human origins is, uh, in my book I talk about, we've evolved to our natural lifespan. We're now at our maximum, 122 is the longest-lived human that ostensibly, uh, is on record. The, so without intervention, we've reached our maximum. But why not now give us what evolution failed to give us? Okay? Why can't we be like other species that are at the top of their game?

   2. JRJoe Rogan49:03

      Are there any factors, when you look at the oldest people that are alive, are there any common factors?

   3. DSDavid Sinclair49:10

      Actually, not really. They, they do seem to have a collection of gene variants that predispose them to get to that long. Uh, there's one called FOXO3 that if, if you've done your genome, we can have a look. Um-

   4. JRJoe Rogan49:21

      23andMe.

   5. DSDavid Sinclair49:22

      Have you done it?

   6. JRJoe Rogan49:23

      I have.

   7. DSDavid Sinclair49:23

      Oh, we should look at it.

   8. JRJoe Rogan49:24

      Why don't we check?

   9. DSDavid Sinclair49:24

      We could tell. Um, you know, you need an A or a T at a certain position. Uh, I've got one of them out of two. Uh, my kid's got, uh, two of my kids out of three have both. So they, if they look after themselves, might have a better chance of living longer. But anyway, these long-lived people, they tend to live a long time no matter what they do. Uh, often they, uh, smoke 'til 90 years old.

   10. JRJoe Rogan49:49

       Really?

   11. DSDavid Sinclair49:49

       Yeah.

   12. JRJoe Rogan49:51

       They quit at 90?

   13. DSDavid Sinclair49:52

       There's a few cases of that, uh-

   14. JRJoe Rogan49:54

       And they live another 12 years?

   15. DSDavid Sinclair49:56

       Right. Right, they-

   16. JRJoe Rogan49:56

       Or more, 22 years, right?

   17. DSDavid Sinclair49:58

       Right.

   18. JRJoe Rogan49:58

       You said 122 years old, that guy?

   19. DSDavid Sinclair49:59

       Well, that lady, that's one, one lady in France. Uh, but I, uh, one of my friends, his, his name is Nir Barzilai, he was with me in Israel, he's got a story of when he asked the centenarian lady, uh, the lady that lived over 100 that he knew, "Why didn't you quit smoking?" And she said, "Oh, all four doctors I went to told me to quit smoking, and they've all died, so I keep going."

   20. JRJoe Rogan50:23

       (laughs)

   21. DSDavid Sinclair50:24

       (laughs)

   22. JRJoe Rogan50:24

       That's hilarious. She, what did she do for a living?

   23. DSDavid Sinclair50:27

       Uh, Jeanne Calment? I forget, the French lady, I don't remember what she did.

   24. JRJoe Rogan50:31

       I would imagine that would play a part, like how stressful your occupation is and-

   25. DSDavid Sinclair50:35

       Yeah.

   26. JRJoe Rogan50:35

       ... you know?

   27. DSDavid Sinclair50:35

       She had a great sense of humor, that was probably part of it. Uh, she used to make jokes with the reporters all the time. Uh, one was, uh, "How many wrinkles do you have?" Uh, she says, "I've only got one and I'm sitting on it."

   28. JRJoe Rogan50:47

       (laughs)

   29. DSDavid Sinclair50:48

       The, the o- the other one I think is even better is, a reporter who was young said, you know, "You're 116, I hope I see you next year for y- for your birthday." She says, "I don't see why not. You seem pretty healthy to me."

   30. JRJoe Rogan51:00

       (laughs) Wow, and she made it to 122. Now, have there been any anecdotal reports of people that lived longer?
10. 1:10:17 – 1:20:08

    Fasting, sirtuins, and quantified self: Oura ring, Apple Watch, glucose tracking

    1. JRJoe Rogan1:10:17

       Do you do, um, intermittent fasting?

    2. DSDavid Sinclair1:10:19

       Yeah, as much as I can. Uh, one of the other guys that was on this tour of Israel with me is Valter Longo, and he's the, arguably the world's expert on this.

    3. JRJoe Rogan1:10:28

       What a great name.

    4. DSDavid Sinclair1:10:30

       Isn't it? He's an Italian guy.

    5. JRJoe Rogan1:10:31

       Valter?

    6. DSDavid Sinclair1:10:32

       Longo.

    7. JRJoe Rogan1:10:32

       Longo.

    8. DSDavid Sinclair1:10:33

       Yeah, like the coffee. Uh, so he-

    9. JRJoe Rogan1:10:35

       Sounds like a guy you call in when you got a real problem.

    10. DSDavid Sinclair1:10:38

        (laughs)

    11. JRJoe Rogan1:10:39

        You know?

    12. DSDavid Sinclair1:10:40

        Uh, yeah. Well, he's, uh, he's written a book, and he is the, probably the world's expert in human periodic fasting. Here's, for everyone who wants to know about what the best periodic fasting, uh, protocol is, there isn't one. We don't know yet. We're right on the cusp.

    13. JRJoe Rogan1:10:56

        Hm.

    14. DSDavid Sinclair1:10:56

        There haven't been enough studies. But there are a few types. Um, I go through them in my book, so, 'cause we, we won't have time to go through all of it. But there's, uh, the, uh, what is it? The 18 or...

    15. JRJoe Rogan1:11:08

        18 hours.

    16. DSDavid Sinclair1:11:09

        Yeah.

    17. JRJoe Rogan1:11:09

        Yeah.

    18. DSDavid Sinclair1:11:09

        So you go eat. If you can go skip breakfast, have a late lunch, that's a good start. That's what I try to do every day. It's not always possible, like when you're in Africa and they're feeding you massive meals three times a day. But the, that's what you wanna do. Be hungry for part of the day. Um, or you can go a little more extreme and skip two days, or weeks.

    19. JRJoe Rogan1:11:26

        And what's the, what's the benefit of being hungry?

Episode duration: 2:19:26