Rewind Your Clock: David Sinclair, PhD Wants To 'Cure' Aging

Aging is inevitable. Everybody grows old. Everyone dies. We accept these statements as fact. But what if they're just stories based on history and our current understanding of biology? What if everything we think we know about aging is about to change? Across the globe, scientists are working on treatments and therapies that are designed to extend healthy human lifespans well beyond what we know today. At the bleeding edge of such breakthroughs you will find David Sinclair, PhD, one of the world’s leading scientific authorities on longevity, aging and how to slow its effects. Returning for his second appearance on the podcast, David is a professor in the Department of Genetics and co-director of the Paul F. Glenn Center for the Biology of Aging at Harvard Medical School. He obtained his Ph. D. in Molecular Genetics at the University of New South Wales, Sydney in 1995 and worked as a postdoctoral researcher at M. I. T. where, among other things, he co-discovered the cause of aging for yeast. The co-founder of several biotechnology companies, David is also co-founder and co-chief editor of the journal Aging. His work has been featured in a variety of books, documentaries, and media, including 60 Minutes, Nightline and NOVA. He is an inventor on 35 patents, has been lauded as one of the Top 100 Australian Innovators, and made TIME magazine’s list of the 100 most influential people in the world. In addition, David is the author of Lifespan: The Revolutionary Science of Why We Age -- and Why We Don't Have To -- a New York Times bestseller that proposes a radical new theory of aging. As he writes: “Aging is a disease, and that disease is treatable.” Last year I convened my first conversation with David (RRP #436), a scintillating and science-heavy primer on all things human lifespan, aging and longevity. It was a runaway hit with the listeners -- and left me wanting to know more. So today we pick up where we last left off, diving deeper into the physiological mechanisms that contribute to biological degeneration. And we go further into the current state of research to better understand what contributes to aging and what can be done to counteract it. Call him a dreamer, but David believes living to 200+ is a plausible reality. If you could double your lifespan, how would this impact how you choose to live? What would it mean for the future of humanity? And for the ecological stability of the planet? The implications are profound. Equal parts philosophic and scientific, this conversation will forever change the way you think about why you age and what you can do about it. And it will leave you armed simple lifestyle practices you can deploy -- intermittent fasting, cold exposure, exercising with the right intensity, and eating less meat -- that will help you live younger and healthier for longer. Brilliant and lovely, it’s an honor to once again share this man's wisdom with you today. So break out that pen and paper, because you're going to want to take notes on this one. The visually inclined can watch it all go down on YouTube. And as always, the audio version streams wild and free on Apple Podcasts and Spotify. I sincerely hope you enjoy the episode. Peace + Plants, Rich Learn more about your ad choices. Visit podcastchoices.com/adchoices

Speaker names marked ? are inferred from speaking time and the show’s known hosts — they are not voice-verified.

• 0:00Rich Roll?

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• 0:44Rich Roll?

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• 1:05Speaker 01

  Nobody has any reason to say that we have this clock that cannot be changed. In fact, what we've learned is that about 80% of our health in old age is due to our lifestyle and how we live, and only 20% is genetic. And actually, your genes are not your destiny. That's the good news. So what that means is, it's up to you, and if you want to be frail, or, to be honest, dead at 80, go for it. We know how to do that. Eat the cake, sit on your fat ass and watch movies. That'll get you there pretty quickly. The problem with today's world is marketing, branding, our own primeval brain. We just want to be relaxed, we want to be fed, we don't want to feel discomfort, and that's leading to a whole bunch of problems.

• 1:48Speaker 01

  And if we're not always telling our body things could be problematic, our bodies don't care. They don't fight against disease, they don't fight against aging. So the bottom line is, you've got to get out of your comfort zone, get your body out of its comfort zone.

• 2:03Rich Roll?

  That's David Sinclair, Ph.D., this week, on the Rich Roll Podcast.

• 2:19Rich Roll?

  The Rich Roll Podcast. Greetings, all you bipedal humanoids. My name is Rich Roll. This is my podcast. Welcome or welcome back. Here's the thing. We take as fact that aging is inevitable. But right now, all across the globe, there are many scientists who are calling this idea into question, hard at work on treatments, on therapies, designed to extend healthy human lifespans well beyond what we know today, and intent on revolutionizing everything we thought we knew about human health. At the bleeding edge of such breakthroughs, you will find David Sinclair, Ph.D., one of the world's leading scientific authorities on longevity, aging, and how to slow its effects.

• 3:04Rich Roll?

  Returning for his second appearance on the podcast, David is a professor in the Department of Genetics and co-director of the Paul F. Glenn Center for the Biology of Aging at Harvard Medical School. He obtained his Ph.D. in Molecular Genetics at the University of New South Wales, Sydney, in 1995, and worked as a postdoctoral researcher at MIT, where, among many other things, he co-discovered the cause of aging for yeast. He's the co-founder of several biotech companies. He's also the co-founder and co-chief editor of the journal Aging, and his work has been featured in a variety of books, documentaries, and media, including 60 Minutes, Nightline, and Nova.

• 3:46Rich Roll?

  He's also an inventor on 35 patents and has been lauded as one of the top 100 Australian innovators and made Time Magazine's list of the 100 most influential people in the world. In addition, David is the author of the fabulous new book, Lifespan: The Revolutionary Science of Why We Age and Why We Don't Have To. It's a New York Times bestseller that proposes essentially a radical new theory of aging. As he writes in the book, "Aging is a disease, and that disease is treatable." Much like our last discussion, this conversation is fascinating. It's all coming up in a couple few, but first...

• 4:32Rich Roll?

  Okay, David Sinclair. So, last year, I convened my first conversation with David. That was episode 436. And I gotta say, that was a absolutely scintillating and science-heavy primer on all things human lifespan, aging, and longevity. It was a runaway hit with the listeners, and it really left me wanting to know more. So today, we're going to pick things up where we last left off, diving deeper into the physiological mechanisms that contribute to biological degeneration. And we go further into the current state of research to better understand what contributes to aging and what can be done to counteract it.

• 5:13Rich Roll?

  Many people call him a dreamer, but David actually believes that living to 200-plus years is a plausible reality. So here's a question for you. If you could double your lifespan, how would that impact how you choose to live? What would it mean for the future of humanity and for the ecological stability of the planet? The implications are simply profound. Equal parts philosophic and scientific, this conversation will forever change the way you think about why you age and what you can do about it. And it will leave you armed with simple lifestyle practices that you can deploy, things like intermittent fasting, cold exposure, exercising with the right intensity,

• 5:55Rich Roll?

  and of course, eating less meat, all of which will help you live longer and live younger for longer. He's brilliant. He's lovely. It is an honor to once again share this man's wisdom with all of you guys today. So break out the pen and paper, because you are going to want to take notes on this one. So without further ado, this is my conversation with Dr. David Sinclair.

• 6:19Rich Roll?

  Good to see you. Thank you for coming out. Thanks, Richard. Thanks for having me out. I'm excited to talk to you again. I want to preface this by saying, if you have not listened to our first conversation, definitely, maybe even hit pause now and go back and listen to that. I never go back and listen to old episodes, but in the case of you, probably mostly because I'm intimidated by you, I had to go back and like... Wrap my head around what we talked about last time. I was like, wow, we covered a lot in that, right? Like, we went, we kind of went through the whole thing. And I don't want to replicate too much of that. But I'm excited to kind of extrapolate on what we spoke about last time. So, welcome.

• 6:54Speaker 01

  Thanks. Sounds good.

• 6:56Rich Roll?

  You were with, you were over doing Laird's workout this morning, right?

• 7:00Speaker 01

  I was. It was brutal.

• 7:02Rich Roll?

  So walk me through it.

• 7:04Speaker 01

  Ah, well.

• 7:05Rich Roll?

  First of all, how'd that come together?

• 7:07Speaker 01

  Um, it was through mutual friends. It was a bunch of us that have known about this for a while.

• 7:17Rich Roll?

  The mythic Laird Hamilton morning pool workout.

• 7:21Speaker 01

  Right. So I remember hearing what it was like and thinking, I really hope I never have to do that in my life. And, and actually, I was right. It was, it was brutal. But, but I do feel really good now. I actually, they say it's, it's good for your mind as well. And I can see why. I'm now just grateful to be alive.

• 7:40Rich Roll?

  Yeah.

• 7:41Speaker 01

  So what that's like is, if, if, if listeners don't know, is you, you start out in a really hot sauna. And I'm not just saying a hot sauna. It is like this temperature of the surface of the sun.

• 7:54Rich Roll?

  Yeah.

• 7:54Speaker 01

  So I normally do 160 degrees at my own gym. This thing was cranked up beyond 250. It was maxed out.

• 8:00Rich Roll?

  That high? I knew he, I knew he said it around 200. I didn't realize it was that hot. Wow.

• 8:05Speaker 01

  Yeah, it's at the point where I was getting pretty dizzy. So you do that. And then you jump into the, you have a shower, you jump in the pool, and you grab, well, first of all, you swim underwater until you're basically out of breath and you want to pass out. Then they give you weights. And then you, you go into the deep end. You're underwater, below the top of your head by, by, you know, maybe half a foot. And then you have to jump up and down. And you think, okay, I can do that. Uh, there are two problems. One is, uh, if you don't make it, uh, you're going to take in a mouthful of water, which is what I did, of course, the first thing. Uh, and then, but then the other problem is you go into this panic mode. I, I don't know if anyone's ever experienced what it's like to drown, but now I know what it's like to drown.

• 8:50Speaker 01

  It is not pleasant. You, you think-

• 8:53Rich Roll?

  You can always let go of the weight and surface.

• 8:55Speaker 01

  There is that, but, but there's only one thing worse than drowning.

• 8:57Rich Roll?

  Standing there and the judgment of Laird.

• 9:00Speaker 01

  Yeah, I would rather drown than be embarrassed and give up. Uh, so, you know, I, I looked like a stupid fish, uh, while a, a land animal in water for a while. I actually found out that I probably shouldn't have gone so far into the deep end.

• 9:14Rich Roll?

  Hmm.

• 9:14Speaker 01

  Uh, that was my first mistake. Uh, but then what, what do we do? We also, uh, warmed up again in the sauna and then we jumped into a big bathtub, uh, with ice, with about a couple of inches of ice on the top. And that wasn't so bad. You know, I, I've talked about cryotherapy before and, and saunas and, uh, hypoxia, but, uh, I've never done it so extreme. You know, I know Will Hoffs is, is the guy to beat, but I, I usually go to my gym, which is just four degrees Celsius. I don't know what that is in, in Fahrenheit, but it's not that cold. It's like your fridge temperature. And I, I found that brutal, but actually going into that ice water, I was, I was fine. I mean, the initial shock, right? You, I can't breathe. I'm going to, you know, and then, but

• 9:59Speaker 01

  maybe 15 seconds later, uh, with Gabby Reese telling me, breathe slowly, breathe slowly. Feel the heat rather than the cold. You can convince yourself that you're warm in this freezing cold temperature. Uh, it actually was great and I, I got to three minutes. Actually, I was going to do two minutes because she thought I was a bit of a, a wimp. Um, got to three minutes and thought, I could just keep going. This isn't so bad. And they were pouring ice on my head at that point.

• 10:23Rich Roll?

  Were you up to your neck?

• 10:24Speaker 01

  Oh yeah. I actually went under for a couple of times there. It was great. And then you get out and you feel great. You feel refreshed, grateful, uh, to be alive. And, uh, yeah, I would do it again in a second.

• 10:39Rich Roll?

  Uh huh. How many, uh, how many people were there this morning?

• 10:43Speaker 01

  There were about 10 of us.

• 10:45Rich Roll?

  Yeah, I've got, I have friends that go to that workout. And I've had kind of a, you know, sort of an open invite to drop by. I mean, I kind of do my own, I have my own workout and it's a bit of a drive for me. So I haven't made it over there, but also in frankness, like I'm scared too. Like, you know what I mean? Like, but what I've, what I've heard was Darren O'Leary there this morning. He's sort of a Laird look alike, like, yeah, Darren, been on the podcast, very good friend of mine. Darren has said that the people who fare well or the best are generally the people that, that go into it with a healthy dose of humility. It's the problems arise when you get these super alpha guys who think they're, you know,

• 11:28Rich Roll?

  basically invincible, like whether they're MMA fighters or Navy SEALs or whatever, and think that they can do anything and kind of attack it from a perspective of, you know, some kind of dick measuring contest of like, I'm going to do this better than Laird or whatever. And they're the ones who get crushed and humiliated.

• 11:44Speaker 01

  Yeah, there's a fair bit of that today.

• 11:45Rich Roll?

  Yeah.

• 11:46Speaker 01

  Yeah. So Darren and I talked about, he's an interesting guy, right? He's sourcing.

• 11:51Rich Roll?

  Yeah, you guys could talk forever.

• 11:53Speaker 01

  We, we will, we will meet up again.

• 11:55Rich Roll?

  Good.

• 11:56Speaker 01

  And yeah, the, Justin Wren was there.

• 11:59Rich Roll?

  Oh, cool.

• 11:59Speaker 01

  You know, my friend, Justin Wren, that was his first time doing it too.

• 12:02Rich Roll?

  Yeah.

• 12:03Speaker 01

  And he was my buddy.

• 12:04Rich Roll?

  MMA fighter.

• 12:05Speaker 01

  Exactly. So Justin, what is it, Fight for the Forgotten? That's his charity. Wonderful, wonderful guy. Check him out. He was my buddy and the first thing I asked him when I was teamed up with him was, do you know CPR? And fortunately he didn't need to rescue me.

• 12:19Rich Roll?

  Yeah, that's cool. Well, you, did you, do I have this right? Like you have some scientific background in thermogenesis, don't you? Did you, do you know Ray Cronis? Did you work with him on some of the studies that, that he did on that?

• 12:32Speaker 01

  Yeah, we published papers together.

• 12:34Rich Roll?

  That's what I thought.

• 12:35Speaker 01

  Yeah. So Ray, Ray and I, interesting story. He was a former NASA scientist, not even thinking about metabolism or, or health. At the time, he was overweight by his own admission. And I met him at a TED Med Talk, 2008 it was. And after my talk about aging and longevity, we were there with Quincy Jones of old people. And he said, David, I've never heard a talk that's convinced me. You know, to change my life, I'm gonna do what you do and I'm gonna be a disciple. Now I thought, okay, you know, Ray, we'll, you know, I'll see you later.

• 13:11Rich Roll?

  Uh huh.

• 13:12Speaker 01

  But he did it. And so now, what is that, you know, over 10 years later, he has changed his life. He's, he's a guru for, for health and particularly cold therapy. And we've published a couple of papers. One is on the metabolic winter hypothesis. The idea that, you know, these days, we, we always look for comfort. And one of the problems is we never experience temperature variation in our lives. We'll, we'll bundle up at night and we'll put on a jacket to go outside. And this is one of the reasons we think that we all have a tendency to get metabolic defects as we get older.

• 13:45Rich Roll?

  Right. Ray's now kind of pivoted more into the nutrition landscape. He's got this new book out with Juliana Hever.

• 13:52Speaker 01

  Yeah.

• 13:52Rich Roll?

  Hellspan, I think it's called.

• 13:54Speaker 01

  Right, Hellspan cookbook.

• 13:55Rich Roll?

  Yeah.

• 13:56Speaker 01

  I gave it to my wife for, for the holidays.

• 13:58Rich Roll?

  You did, cool.

• 13:59Speaker 01

  Yeah, it's really great. I really liked those guys, both of them. They're, they're making good combination.

• 14:05Rich Roll?

  Mm hmm.

• 14:05Speaker 01

  Cause Juliana's the, the cook and Ray's the brain.

• 14:09Rich Roll?

  He's, yeah, exactly. It is, it is a good mix. They live like right up the street here.

• 14:13Speaker 01

  Oh, do they?

• 14:13Rich Roll?

  Yeah, they've been on the podcast. Um, cool. Well, I think it's interesting that you, you did the Laird and Gabby workout this morning with this combination of like sauna and ice baths. So maybe a good, you know, first thing to explore is the relationship of those types of therapies on aging and longevity.

• 14:35Speaker 01

  Right. Well, the bottom line is you've got to get out of your comfort zone, get your body out of its comfort zone. Hormesis is what we call it.

• 14:43Rich Roll?

  Right.

• 14:43Speaker 01

  And the problem with today's world is marketing, branding, our own, just our own primeval brain. We just wanna be relaxed. We wanna be fed. We don't wanna feel discomfort. And that's leading to a whole bunch of problems. And if we're not always telling our body. Things that could be problematic, our bodies don't care. They don't fight against disease, they don't fight against aging. So these treatments and these crazy things that I did today are all about turning on the genes that we work on. We could talk about those in a minute. But this is the revolution that's happening. And there's a whole bunch of people, your listeners, for example, are realizing that one of the

• 15:25Speaker 01

  biggest problems in our lives is that we've just been, you know, handled with kid gloves. And the food we eat is also not stressed out. And that combination just turns us into mush.

• 15:37Rich Roll?

  It's interesting when you say the food that we eat is not stressed out. So that's about kind of taking in stressed foods to prompt this hormesis type effect through our nutrition? Or, you know, explain what you mean by that.

• 15:54Speaker 01

  Right. Well, we were working on resveratrol. The resveratrol story is what I first was known for in the science world. And we discovered a whole bunch of different plant molecules. One of them is resveratrol from, found in red wine. But there are a lot of others. There's quercetin from onions, for example. And they all activate these longevity enzymes that we have in our bodies, and they're found in plants as well. And we were trying to figure out, why would it be that these so-called polyphenolic compounds like resveratrol and quercetin, why would our bodies benefit? Or why would a mouse benefit by eating these molecules? And what we came up with was the concept of xenohormesis. Xeno means between

• 16:38Speaker 01

  species, and hormesis is what doesn't kill you makes you stronger. And it's, even though it's a mouthful, what it explains so much is that when our plants are stressed that we eat, we've probably evolved to sense when the environment and our food supply is running out, or potentially running out. So if you're picking olives off a dry You know, a hill or you're eating fruit that's just had a massive drought. You're gonna have molecules in that food that'll tell your body, hey, these plants may not be around for the next month. And that was our explanation. And it really does make a lot of sense and is fitting with a whole bunch of data we've had over the last couple of centuries.

• 17:24Rich Roll?

  That's like different species communicating with each other through some, you know, unheard language.

• 17:31Speaker 01

  It is, it is. And actually, what it means is a couple of things. One is, don't eat foods that are grown under perfect conditions. That works well for the growers because they get food much more quickly. Think of the lettuce that you buy that's in the greenhouse that's never been stressed is just watery, white and watery.

• 17:50Rich Roll?

  Right.

• 17:51Speaker 01

  Avoid white and watery. What you want is denser colored food. The color is actually an indicator that you've got these polyphenolic beneficial molecules. So I like to buy foods that are locally grown, organic, and typically grown in conditions that are not perfect.

• 18:11Rich Roll?

  So what is it about it being locally grown or being organic that enhances the hormesis impact or the stress response in the plants? Like, couldn't you, could you figure out a conventional way of growing food where at the last minute you stress them before you pick them or something like that? So you're getting an enhancement of those polyphenols or whatever it is that you're looking for?

• 18:32Speaker 01

  That's exactly right. That's what I think we should be doing. And there's a business idea.

• 18:38Rich Roll?

  Okay.

• 18:38Speaker 01

  And in fact, Laird was telling me just an hour ago that, that I didn't know this, that people who grow oranges and know what they're doing, drive a nail into the tree. Uh, I think it was a day or so before they picked the fruit and that gives it these extra.

• 18:55Rich Roll?

  Oh, wow. That's, that's interesting.

• 18:57Speaker 01

  Yeah. So we, we got to harm the plants just a little bit, but it doesn't need to be all the time. It can be just before you pick them and think about grapes, right? What we do when we want to have great wine is we pick them just as they're stressed that we, they, you try to pick them when there hasn't been rainfall for a little bit. And then they fill up with these great tasting molecules, but also these xenohormetic molecules as well.

• 19:20Rich Roll?

  So how does that, I mean, when, when, when we're told like, listen, you should eat organic food. It's really about trying to avoid the pesticides and everything else that gets packed into conventionally grown foods. But what is, what is it about organic that relates to this?

• 19:34Speaker 01

  Well, you know, there's organic and there's real organic. I'm talking about the plants that, you know, may have had a grub eaten or are exposed to too much sunlight, that kind of thing, being out in rougher conditions.

• 19:46Rich Roll?

  Yeah. Hyper organic.

• 19:49Speaker 01

  Right, right, right. Not, not, not pseudo.

• 19:51Rich Roll?

  That's the name of the new company.

• 19:53Speaker 01

  All right. Let's do it.

• 19:55Rich Roll?

  Yeah.

• 19:57Rich Roll?

  That's cool. Well, when you look at Laird, I mean, he's sort of a, an experiment in motion, right? Like, what is he 55 now, I think? Doesn't look a day older than he did, you know, 10, 15 years ago, and he's still killing it. And I would say that he's probably a pretty good example of, of somebody who's practicing a lot of the things that you talk about. I mean, I don't know what his, you know, supplement routine is with respect to, you know, some of the research that you're doing. But in terms of his daily exercise regimen and lifestyle habits, uh, it seems to be, you know, to comport with the things that you talk about often.

• 20:32Speaker 01

  Yeah, right. He's the orange tree with the nail in it every day. But I, I totally believe it. Um, and you, but you, you don't just do it with hot and cold. And you don't just do it with, um, what you eat. There are other things you can do, like when you eat. You can also, and he's doing plenty of exercise, which is another thing. And one of the, the breakthroughs that we've had in the longevity field is that we used to think, you know, let's go back 20 years ago, that exercise was something that made your blood flow better and made you healthier, uh, that eating less food was healthy because it. Lowed inflammation somehow. What we've realised is that all of these things are working through the same mechanisms. And it goes back to work that we did in my lab

• 21:15Speaker 01

  in yeast cells, you know, a little fungi that we grow, that we use for bread and beer. What we showed, and this is going back to 2003 now, is that there's one gene that controls longevity. It's got a name called PNC1. It makes this molecule called NAD, which is very healthy, turns on defences. We found that these yeast cells live longer when you gave them a bit of stress. So if you turn up the incubator to 37 degrees Celsius instead of 30, they live longer. Or you starve them a little bit of, or take away a little bit of the amino acids in their food, or what else could we do? We could restrict the amount of sugar that they were eating. That all made them live longer, but it all worked through this one genetic pathway. And that was a breakthrough at the time because, you know, even today, most people don't realise that all of these things that we

• 22:00Speaker 01

  do are converging on this master regulatory pathway for our health.

• 22:05Rich Roll?

  Is that part and parcel of this, you know, kind of singular information theory of aging that is, you know, the sort of the foundation of your work?

• 22:15Speaker 01

  Yeah, it all connects. It's all slowly coming together. It's taken 30 years of work, but we're getting there. I can see the end of the tunnel. And what is interesting is that, so this NAD molecule is the fuel for a class of enzymes that acts like the traffic cops in the cell. They they send out the troops to repair and fix things. And one of the maiden things they do, we found, is they control the expression or control information in the cell. Not the genetic information, but how the genetic information is controlled. And these genes are called sirtuins. So sirtuins, you can

• 22:55Speaker 01

  think of as the pianist that plays the genetic piano. And when they're not active, the pianist becomes complacent, makes a lot of mistakes and ends up becoming demented. And that is what I believe is a large driver of the aging process. But if you're always activating your sirtuins. The pianist keeps playing the concerto for much longer and we stay younger.

• 23:19Rich Roll?

  Right. We talked about this last time. The analogy we used wasn't the pianist. I know that's like the title of, I think, the second chapter in the book, right?

• 23:27Speaker 01

  Demented pianist.

• 23:28Rich Roll?

  The demented pianist, where you explain all of this. The metaphor that we used was, was, you know, highway traffic, right? And getting dispatched, you know, away from their, their true role to kind of deal with crises, potholes in the roadway and whatnot. And then the signaling, you know, getting screwed up. And then basically all of the kind of traffic copping going haywire and these, these, you know, the NAD isn't going where it's supposed to go, be going and the sirtuins aren't where they're supposed to be and the whole kind of system breaks down.

• 24:00Speaker 01

  That's right. And we first discovered this, I was at MIT as a postdoc originally, moved to Harvard in 1999. Those years were, were formative. What we discovered in yeast cells, it's incredible, right? You can learn from a little fungus, these big concepts. These sirtuins in the yeast cells were maintaining the identity of those yeast cells and making them stay young and healthy for longer by keeping the gene piano working for longer. Now, what we also realized was that you can distract them from their main job. The pianist can get distracted. You know, imagine, you know, you, you start trying to, you know, whistle or get in, get in the face of your pianist. It's essentially the same. And what

• 24:43Speaker 01

  is a major distraction for these sirtuins in their normal job is broken chromosomes, broken DNA, DNA damage. And we know that DNA damage can accelerate aging. Anyone who's lived in California or Australia, like we have, knows that DNA damage from the sun will accelerate aging. But no one has ever fully understood why. And it's been a mystery. And mutations don't seem to be the main driver. This is the old theory. So what I think is going on is that these Breaks in the chromosome, it's DNA damage, is distracting these sirtuins from maintaining the symphony perfectly. They get distracted, they go off and do stuff, fix the chromosome. And then, most of them come back and keep playing the piano, but some of them never

• 25:28Speaker 01

  make it back to where they should. And over time, that's cumulative, and you end up with a cacophony.

• 25:34Rich Roll?

  So, the goal, the job, the mission, is to maximize the efficiency, to really optimize the sirtuin functionality?

• 25:44Speaker 01

  Right. And the way to do that is to make the body think that it's, it could run out of food, or has to run away from a saber-toothed tiger. And that all relates back to the activity of these sirtuins.

• 25:57Rich Roll?

  Because then they're not distracted by these sort of frivolous situations, and they're, they're focused on the, the, the most important job that they're kind of created to deal with.

• 26:07Speaker 01

  Yes. And the other way to think of it is, without enough fuel, and NAD is their fuel, this little molecule called NAD. If you don't have enough NAD, they are very slow at doing their job. They kind of, they get detached from what they should be doing. And then they, they drift off through the liquid in the cell, and they don't have enough energy to, to fully fix the DNA quickly. And they don't have enough energy, we think, to come back to where they came from. But if you do have all the energy, and they're in their prime, still the youthful sirtuins, they can fly off and come back. But it's, without the fuel, the NAD, or, you know, resveratrol's also an activator. That's

• 26:47Speaker 01

  one of the things we figured out in the 2000s. So, the combination of the fuel and the activator, resveratrol and the NAD, is a fantastic combination, we think, for maintaining that, that epigenetic symphony, as we call it.

• 27:01Rich Roll?

  Right. So, what is the state of the union when it comes to, to the scientific research on sauna therapy, you know, cold therapy, and its impact on NAD and sirtuins, and, and thus aging, or anti-aging?

• 27:17Speaker 01

  Uh, that's a really good question.

• 27:18Rich Roll?

  You just got a big smile on your face.

• 27:20Speaker 01

  Yeah. I, I, I can, I can see why you're so good at what you do.

• 27:24Rich Roll?

  I'm just trying to follow my curiosity here. I'm trying to keep up, and, and I really want to, like, understand this. So, anyway, go ahead.

• 27:34Speaker 01

  Well, so the connection is that the Surtuans are actually

• 27:42Speaker 01

  waiting for more NAD production. And remember that old yeast cell story that I told you about? There was one gene that was turned on by temperature and by low amino acids. That gene makes NAD, okay? In our bodies, we have the same equivalent gene. It's called NAMPT, N-A-M-P-T. And we discovered, it's now 2007, that when you stress human cells in the dish and in the body as well, that you turn it on. So NAMPT comes on and it makes more NAD for the body and the Surtuans can do a better job. So NAMPT is really interesting. Most people don't know about it or talk about it, so I'm glad you brought it up. That's why I'm smiling. Yeah, we definitely didn't talk about this last time.

• 28:26Speaker 01

  Right, so I haven't talked about it publicly. NAMPT is the master regulator of NAD production. It's what we call rate limiting step in making NAD from precursors like vitamin B3. And so we took human cells, we put them in the dish and we stressed them out. So we gave them not enough sugar, we gave them too much temperature, what we call heat shocked them. And on came this NAMPT and they made more NAD. So what I think could be going on is that the stress on the body when I'm, you know, 200 and whatever Fahrenheit and then jump plunging into basically zero degree Celsius, that is making my body make more NAD, essentially mimicking the effects of exercise and hunger, just a different way,

• 29:11Speaker 01

  and making my Surtuans work optimally. And that is something that I think is underappreciated, that this one gene is probably the main cause.

• 29:26Speaker 01

  Of the benefits of all of the things that we have figured out over the last 2,000 years of being healthy.

• 29:31Rich Roll?

  And is there an understanding of the relationship between the hot and cold? Is it that combination that makes it effective? Could you just do the sauna or just do the cold therapy? Or like, how does it, you know, has that been explored?

• 29:42Speaker 01

  Not well.

• 29:43Rich Roll?

  Yeah.

• 29:43Speaker 01

  No, no, and I'm asked all the time, what's the best combo of diet?

• 29:48Rich Roll?

  Right.

• 29:48Speaker 01

  Exercise. We're figuring it out.

• 29:50Rich Roll?

  Figure that out and then, you know, you, the keys of the kingdom arrive.

• 29:54Speaker 01

  Yeah.

• 29:54Rich Roll?

  But you have Rhonda Patrick talking about sauna and then you have the Iceman Wim Hof talking about the cold therapy. And now you have people like Laird who are combining these two. And I'm just trying to get a sense of like, what is the ultimate stress or, you know, hormesis inducing protocol that's going to activate this NAD producing signaling mechanism?

• 30:16Speaker 01

  Right, so we need to figure that out, but I have a philosophy that drives what I do and what I talk about. And that is that you don't want to do the same thing over and over again. Mix it up.

• 30:27Rich Roll?

  Right, because you, you acclimate to that, right? And it's no longer, it's no longer creating the stress response.

• 30:32Speaker 01

  Exactly, so I don't exercise every day, not that I could, but I don't.

• 30:36Rich Roll?

  It's a convenient excuse.

• 30:37Speaker 01

  Yeah. Really true, but you gotta, you gotta pulse it. Right, because as soon as the body gets used to what, you know, I'm in this ice bath and after three minutes, I'm like, what's the big deal?

• 30:47Rich Roll?

  Right.

• 30:47Speaker 01

  You gotta, you know, switch it up. And that's why I think that the best thing that we know right now is that you want to do some, some exercise, then you want to do the sauna, then you do the ice bath. That's what I do. And until I know more, I'm going to keep doing that.

• 31:04Rich Roll?

  Right. Similarly, I would imagine, you know, when you look at Walter Longo and his fasting mimicking diet and all the science that's emerging around intermittent fasting, I mean, the, the benefits of that are kind of boiled down to hormesis, right? You're trying to create a stress response that activates certain, you know, pathways in your, in your system that, that relate to aging or anti-aging. But I would imagine that you could, you could develop a set point with that as well, kind of acclimate to that and get used to it. And then you're no longer experiencing that benefit. Do we, is that, is that, is, does it work that same way with the eating?

• 31:39Speaker 01

  Well.

• 31:42Speaker 01

  It's it's complicated because there there are two experiments that have been done. Uh, one is to consistently just give mice low-grade food, basically mix their food with cardboard cellulose. And that works. So if mice are nibbling all day on low-calorie food, that still works. So you don't have to do intermittent fasting for this to work.

• 32:01Rich Roll?

  You never get used to not eating.

• 32:03Speaker 01

  Yeah, yeah, your body will still respond. Uh, but at least we we understand what's going on. And again, it's this NAMP-T gene in large part that's turned on when your body doesn't have enough glucose and and insulin is being produced. But also this intermittent fasting, the reason I like it, and I, you know, Volta has been an old friend. We used to, by the way, we used to study yeast cells together. This is where we both came from.

• 32:28Speaker 01

  The intermittent fasting for me is is better because it means you can eat instead of seventy percent normal calories, you can eat ninety-five percent or a hundred percent calories. You just have to squeeze it into a window of a few hours to be optimal, and that's just easier to do.

• 32:43Rich Roll?

  Right.

• 32:44Speaker 01

  And in the mouse world, if we do calorie restriction, which is this low-quality diet, a low-calorie diet, of course, versus intermittent fasting, uh, they both work about the same that, you know, you can argue about minutia, but basically they all extend lifespan. But the mice that are on intermittent fasting can eat a lot more in their lifetime.

• 33:03Rich Roll?

  Yeah.

• 33:04Speaker 01

  And, you know, if if you're not eating food and enjoying life, you know, it's not it's not worth it probably for some of us.

• 33:10Rich Roll?

  But I need to get, I'm hormesis, hormesis. I'm gonna starve myself.

• 33:15Speaker 01

  Well, yeah, I I'm I'm skipping one to two meals a day and and it's it's changed my life. I feel great. And a lot of people say, like, it it makes me feel queasy or my stomach's burning. I found I I get used to it. And if you if you find that it's too hard, try a cup of hot water. I think coffee is is great, tea, and that gets me through the morning.

• 33:35Rich Roll?

  Mm-hmm. Yeah, I've been playing around with it and experimenting with it for a while. And and I found that that, you know, it's so much of this is psychological and mental. Like, I I'm now in a place where, you know, there's plenty of days where I won't eat until dinner. And it's not because I'm trying to provoke suffering. Like, it's just, I'm I'm not even really thinking about it. Where you really realize realize it. And I know you posted about this on Instagram the other day is when you fly, when you get on a long plane and I use those generally as opportunities to play around with this thing because I'm not going to eat the food that they're serving on an airplane. And it's hard to get healthy food in airports and the like, but for the most part, most flights

• 34:18Rich Roll?

  are, you know, four to six hours, unless you're going to Australia, which we're going to talk about. It's not that big of a deal, right? And then when the, when the flight attendant kind of repeatedly drops by and says, are you sure you don't want anything? And the look on their face, they're just like amazed that you're not eating. And you're like, it's not that big of a deal.

• 34:36Speaker 01

  Right. They're saying, but, but you've paid for this. It's free. You have to eat it. Do you want some ice cream and cookies? No, go away.

• 34:44Rich Roll?

  The more you say no, the more they come back.

• 34:46Speaker 01

  They're insulted, I think. Yeah, but I agree with you. It's a moment to really test yourself because you're, you're sitting there and all you've got to think about is the food and the person next to you is eating.

• 34:57Rich Roll?

  Right.

• 34:58Speaker 01

  And then, then you really test your mental will. And actually I use that as a way to test myself. And one of the things I do is I think, you know, it's fine to eat now, but what do I want to look like, feel like a day, a week from now, 30 years from now. And that allows me to help my future self.

• 35:16Rich Roll?

  Yeah. Well, you don't look a day older than the last time we spoke, which was at least a year ago, I think. Yeah. So you're 50, 51, 50?

• 35:25Speaker 01

  No, I'm still, I'm still 50, but yeah, no gray hair. I'll let you know.

• 35:29Rich Roll?

  No. Yeah, definitely. Not a gray hair on your head yet. And what, maybe this is a good place to talk a little bit about the difference between the biological clock and what you call Horvath's clock, right? The Horvath measure of aging?

• 35:49Speaker 01

  Yeah.

• 35:49Rich Roll?

  Can we talk about that?

• 35:50Speaker 01

  Yeah, that's really important. It's a massive breakthrough in the field of aging for many, many reasons. One of the big things that's held us back in studying aging is we didn't have a real measure of what aging was. You could look at a mouse or a human and say, okay, they look young or they look old, big deal. But we needed a mathematical and a, a non-subjective measure. And we finally have that, finally. Until recently, all we had was some blood tests that tell you you're, you're looking, okay, you're looking healthy, you're on the right track. But the clock changes everything because it's a mathematical. Clock and actually Horvath, Steve Horvath is one of my very good friends, great guy.

• 36:33Speaker 01

  He's a mathematician by training and somebody got their clock measured by him. Well, I'll tell you in a minute about how the clock works, but someone said, oh, I got a really bad result on my clock. I'm biologically 10 years older. Are you sure the clock is right? And he said, as in true German form, he's, I think Austrian, actually, he said, there's a greater chance that the earth will be hit by a meteorite tomorrow. So that's how good this clock is and it's Not so hot of a bedside manner, though. No, no, no, but he's got a great dry sense of humor. So what we've got actually is, and the beautiful thing about it is it's not just helpful to be able to say this is how old an animal or a human is biologically, but also it comes back to this information

• 37:15Speaker 01

  theory of aging. The epigenetic information is what I think is lost during aging. That's the most important thing. Basically, the pianist, not the piano. Right. The clock is measuring the pianist's state of mind, right? And when, so what Steve's doing with his clock, he's measuring how demented the pianist is. So that's of course a metaphor. What's actually happening in real life is that our DNA has chemicals on it that tell which gene to be on and off. That's basically the notes for a symphony, the score. Right. But when you're born, you have a certain pattern of these, what are called methyls,

• 37:57Speaker 01

  these are little chemicals, just carbon and three hydrogens that bond to the C letter. You know, on DNA, there's ACTG. Right. So the Cs get this methylation, it's called, just a chemical that sticks there and doesn't come off unless the body takes it off. It's a permanent mark. And that's what says that gene needs to be switched off. That gene in your brain only comes on in the liver. So keep that off for the rest of your life. And I think that that pattern that changes over time is what drives aging. Now, what Steve found independently from me is that if you can read the pattern of those methyls. It'll change over time. And if you use machine learning and say, okay, this is the pattern of a 50 year old, 20 year old, even a five year old, you can draw a straight line.

• 38:42Rich Roll?

  Mm hmm.

• 38:43Speaker 01

  And then, once you've got that straight line, he can, here I can take your blood, map your methylation pattern, as we call it, and place you exactly within a few percent error of where you are on that curve or on that straight line. And then we can say you're likely to die in July 2050.

• 39:00Rich Roll?

  Oh, wow. I would imagine that gets more and more accurate every day, right? As the data set grows?

• 39:06Speaker 01

  It is. We're learning a lot. We've got now clocks for human skin, the blood. In my lab, we've got mouse liver and kidney. But also, here's the amazing thing. We didn't know this until just a couple of years ago, that you can take a dog's clock and use it to predict the age of a human or a sheep or a bat. What is, you know, that that sounds fanciful. But what that's telling me and Steve is that there's a universal underlying clock of aging in mammals at least. And I think it probably goes all the way back to jellyfish. We're going to do a jellyfish clock because jellyfish can be immortal.

• 39:45Speaker 01

  So we want to figure that out, how that works. But what we basically have converged on, we think, is that I'm saying, I think we understand what drives aging mainly is the loss of that perfect pattern of which genes are on and off when we're young. And that Steve has figured out, has figured out a way to actually quantify that.

• 40:06Rich Roll?

  Hmm. So what is your, what is your age according to the Horvath method?

• 40:10Speaker 01

  I don't know yet.

• 40:11Rich Roll?

  And when are you going to die? What do you mean here? You don't know?

• 40:13Speaker 01

  No, no, I've been too busy. But no, I've, I've done just the, the old fashioned blood tests and, but I'm going to do it. I'm not avoiding it. I'll tell you what we are doing that I haven't told anybody. It's a little bit of a secret, but why not? Right now, the test costs a lot of money.

• 40:30Rich Roll?

  Hmm.

• 40:30Speaker 01

  Um, I think a really good deep test would cost at least 300, sometimes 1,000 bucks to do. So it's not cheap. And you can't do it every week, you can't do it every month. But we're working in my lab, we just had a breakthrough, we think we can bring it down to five or $10. And then you could do it at home.

• 40:49Rich Roll?

  Right.

• 40:50Speaker 01

  If you're, if you're brave enough.

• 40:51Rich Roll?

  There's another business for you.

• 40:53Speaker 01

  Yeah, well, that, that will be hopefully a business. That's one of the reasons we're doing it, but also right now it's too expensive to measure the age of a million people. But without technology, we could do that.

• 41:05Rich Roll?

  Right.

• 41:05Speaker 01

  And then things get interesting, then we can say, people who drink this coffee that I'm holding in my hand. How do they do? Does their clock go backwards or not? And finally, we can figure out within a short period of time, what things work for slowing or reversing aging. And there was a, a study that Steve was on recently, last year, that at least suggested with a small number of people that a treatment in humans could actually reverse the age of those people by at least a couple of years.

• 41:35Rich Roll?

  Wow. Yeah, then the data becomes unbelievably valuable, right? It's, it's less about what the consumer finds out about his or her life and more about the value of that data set and what you can extrapolate from that.

• 41:46Speaker 01

  A lot of people are scared to measure their age because I don't want to know that, you know, even myself, I will admit, I'm, I'm kind of scared to look.

• 41:53Rich Roll?

  Yeah. What would happen if it said, you know, here, here you are, the, the anti-aging longevity guy, you're going to die in two years.

• 42:00Speaker 01

  Yeah, that would be.

• 42:01Rich Roll?

  That would not be good for.

• 42:02Speaker 01

  Be a bad day.

• 42:02Rich Roll?

  For business.

• 42:04Speaker 01

  Yeah, well, you know, I, I don't live perfectly, that's for sure. I don't, every day I jump up and down in a swimming pool like I probably should be, and I'm on planes a lot, which is not good. I'm sitting down a lot, I'm typing, so there's, I might actually be older than, than I look, who knows? I, I will, I will tell everybody when I get that data. But here's, here's the really important point, Rich, which is that data is important, right? I'm data-driven as a scientist, but everybody with their body should be cognizant of how they're doing. Just ignoring aging is not going to make it go away or slow it down. So what happens if you find out that you're a bit older than you actually are based on your birthday candles? What does that mean? Is it, do you just go to bed and get, have depression?

• 42:48Speaker 01

  No, this is enabling, what it means is that you can actually alter the trajectory of your life. That trajectory that you're on. It's not fixed. Just because I say you're going to die beginning of 2050, that's if you don't change anything. But you can bend the needle and the things we're talking about today, the hormesis effects, we already know can actually change the slope.

• 43:11Rich Roll?

  Right.

• 43:20Rich Roll?

  Since we last spoke, has there been any interesting breakthroughs or new studies or or science that has kind of shifted or or expanded your perspective on any of the things we talked about last time?

• 43:33Speaker 01

  Uh, yeah, lots. You know, every day I before I get out of bed, I'm actually reading scientific papers. Can you believe it? Pretty much every day I'm excited by something new. There was something a couple of weeks ago that came up that that I'd been hoping to see for at least 12 years. And that was to find out, why does resveratrol activate the sirtuin enzyme? Why is that? So one idea is that we're sensing the stress and adversity of our food. But we also have hypothesized since we first discovered resveratrol and its role in aging, anti-aging, is that it's probably mimicking something that our

• 44:13Speaker 01

  bodies make. We call it the endogenous activator, the elusive endogenous activator. And what this paper showed was that the byproducts of the what we call lipolysis, the breakdown of fat when you're when you're hungry, produces mono unsaturated fatty acids, the kind that you can get from olive oil.

• 44:36Rich Roll?

  Right.

• 44:37Speaker 01

  Those molecules circulating in the blood are about 1,000 times more potent than resveratrol at activating this longevity enzyme. So what does that tell us? First of all, resveratrol is pretty cool. You can mimic your body's fasting state by by ingesting it. But also, it means that we've kind of been vindicated because we got a lot of crap for resveratrol in the early years.

• 45:01Rich Roll?

  If you if you Google your name and resveratrol, there's a there's a lot of shit talking coming in your direction for some earlier stuff from years ago.

• 45:09Speaker 01

  Well, yeah, and it's been it's been a brutal part of my career. But we've always gone back to the bench and done better science because of those challenges. And one of the big challenges in my career was that resveratrol We said it activates the enzyme by actually literally sticking to and binding to it physically and making it more active, like a Pac-Man would move faster. And then a couple of companies came out, big, big pharma companies, and their scientists said, literally, that is bull.

• 45:41Rich Roll?

  Right.

• 45:42Speaker 01

  And that's brutal when that happens. And everyone, almost everybody except close friends, said, oh, we're going to believe the companies and David's wrong. And that, that's a tough time in anyone's career. And my lab shrank down to about a fifth of its size and couldn't get great money. But we fought back. We, we, we went back to the bench. I got out of bed eventually. And I had a student called Basil Hubbard, who's now a professor in Canada. He didn't give up. Everyone else in my lab was kind of like, oh, we're screwed. Let's get out of here, sinking ship. He said, no, what, you know what, I'm going to test this. And he, he worked really hard and figured out that the, the experiment that we originally did to show that resveratrol was activating the enzyme in the test tube was not an artifact,

• 46:26Speaker 01

  and that it was actually real. So we published that in the journal Science in 2013. And so the, the scientific hubbub went down.

• 46:34Rich Roll?

  Mm hmm.

• 46:35Speaker 01

  Basically, we, we were, you know, largely accepted that we were correct. But out in the media, you know, no one, no one cares about correction of a scientific idea.

• 46:46Rich Roll?

  Yeah, of course not.

• 46:46Speaker 01

  It's all about the controversy that's interesting. And so that's still out there in the world. So anyone listening who, who knows that this was controversial, we've actually scientifically resolved the controversy, whether it's true or not, it is true. But it still left open the question, is there something in the body that we make that activates the enzyme like resveratrol does?

• 47:06Rich Roll?

  Mm hmm. So this new study, then, basically, kind of, you know, what I infer from that is that we should be eating monounsaturated fats, or that we should somehow be trying to trigger this lipolysis, you know, situation, so that we are, you know, creating this impact that we're trying to have? I mean, what, what do we do with this information?

• 47:27Speaker 01

  Yeah. Well, I think the, the lipolysis we're going to be doing with intermittent fasting anyway, it's up and down. But I think that the most exciting thing about the paper is that they found that oleic acid from olive oil. Is also a very potent nano molar for the aficionados activator of Sert-1. So what does that mean? That means that when you eat olive oil, you're actually activating your sirtuins quite potently because it's also, just like resveratrol, mimicking this lipolysis effect. And maybe, and I and the authors of that paper have written, that this could explain why the Mediterranean diet is so healthy.

• 48:09Rich Roll?

  Mm hmm. Or alternatively, in lieu of olive oil, you can get the same result via resveratrol.

• 48:16Speaker 01

  Well, yeah. So one thing that occurred to me was, so I've been taking resveratrol for over 10 years now, and I'm glad I have. Maybe I should have been taking a little bit of olive oil as well, but resveratrol has no calories. So I've basically been drinking olive oil for the last decade without the calories.

• 48:33Rich Roll?

  Right. That's a good thing. What is, we talked a little bit about this last time, and I think it's worth exploring a little bit more. What is the difference between taking in resveratrol via, you know, red wine versus a supplement in terms of bioavailability and your body's ability to kind of metabolize it?

• 48:55Speaker 01

  Yeah, so resveratrol is unfortunately a pretty insoluble molecule. Now, in the plant, what the plants do is they put a sugar on it, and it's quite soluble for the plant, but for some reason, we like to purify it away from the sugars. Well, not for some reason, because if you don't, it's a sticky horrible mess. So we isolate resveratrol that's free and clear of all these other bells and whistles that the plants like to stick on them. But what we're left with is basically a crusty, dry powder that doesn't get absorbed by the body very, very much. And even if it does, it gets basically gotten rid of by the liver. So what we had to learn early on, even for worm studies, when we were showing resveratrol extends the worms, is you have to dissolve resveratrol in some sort of solvent.

• 49:40Speaker 01

  So for worms, we use a thing called DMSO. In humans, we found in the early 2000s that you, if you mix it with a fatty meal, and that's true for mice as well, you get about five to 10-fold the levels. And so I always mix my resveratrol with something that's got a little bit of fat in it, like a homemade yogurt every morning. And what I've noticed is that the studies in people That have not shown the benefits are the ones where they've just given a dry capsule to the patients or the subjects. And those that work are those typically that are given it with a meal or something that the resveratrol would dissolve in.

• 50:17Rich Roll?

  Right. So there is some sense that that that definitely increases the bioavailability and absorption.

• 50:22Speaker 01

  No question. We did these clinical trials a long time ago as we were working our way to making a drug. But we actually, we ended up making synthetic molecules that were a thousand times more effective than resveratrol. We didn't know at the time we were making the equivalent of olive oil or like acid. But I guess now we do know that. Those molecules actually went into clinical studies with with humans. That's also not very well known. And there's a the skin condition psoriasis. It worked really well. They popped a pill of these activators and one of these activators and the patients did better. Now, I'm still hoping by the time I die, I'll have one of these medicines on the market. We're not there yet. And that's actually one of the brutal take home messages,

• 51:03Speaker 01

  actually, is I don't want to complain because I've been very lucky in my life. It's it saddens me that that in science, you can be derailed by decade for a decade by, you know, by your naysayers. And I'm hoping to get things back on the rail. Seems like so far so good.

• 51:22Rich Roll?

  Well, the last time we spoke, you know, this book had not come out yet. Now it's been out. You've been doing the you did the book tour thing. And, you know, I kind of canvassed some of the press around that. And it's interesting because it's my sense is that, on the one hand, kind of in popular culture, you're being feted and celebrated for this book and your work. Breakthroughs, you know, this bold, you know, taking this very bold position that that aging is reversible, that we're on the precipice of new science and breakthroughs that are going to revolutionize how humans live their lives and think about their lives. And on the other hand, you know, some pushback from the conventional scientific

• 52:07Rich Roll?

  community and some grumbling amongst, you know, the old guard saying, not so fast.

• 52:13Speaker 01

  Exactly.

• 52:14Rich Roll?

  You know what I mean?

• 52:15Speaker 01

  They hate fast.

• 52:15Rich Roll?

  Yeah, you're you've got your your foot on the accelerator. And they seem to be saying, you know, slow down, you're you're you're kind of out over your skis here.

• 52:24Speaker 01

  Yeah, that's true. But that's. You know, so be it. We have a certain amount of time on this planet. And I'm going as fast as I can. The other thing that most scientists don't realize is sometimes it takes us a decade to publish our work. So we know, I know a lot more about what we're working on than other people. And when they say to me, oh, David, or say behind my back, David's out over his skis, they only think that I know what's published, but we've got all this other stuff. So when we were challenged by these companies, even though it was sad, I had a whole body of data from my lab that said, I'm not, don't be so sure of yourself. But yeah, it's tough as a scientist, especially one at a conservative university like Harvard.

• 53:10Speaker 01

  You know, I often get my knuckles wrapped because I'm out there.

• 53:13Rich Roll?

  Right.

• 53:13Speaker 01

  But I do it not because I'm seeking fame or anything. I'm a pretty shy guy. But I do want to see technologies adopted within our lifetime. You know, it's fine, future generations will do well. But I really do think that it would be a real shame if our generation was the last to live a normal lifespan.

• 53:34Rich Roll?

  You would think that Harvard would celebrate this. I mean, don't they want people that are sort of breaking paradigms and pushing the envelope? And what is the purpose of a lab? If not to test the limits of our of our understanding and to kind of, you know, dream boldly?

• 53:51Speaker 01

  Yeah. Well, so in Harvard's defense, what gets them riled up is when I get misinterpreted by mainstream media. So I rarely now talk to

• 54:03Rich Roll?

  That never happens.

• 54:04Speaker 01

  Yeah, it's tough as a scientist because you say, here are the facts, here are the facts. And the headlines out for me typically is Harvard scientists says we're all going to live to 150.

• 54:13Rich Roll?

  Right.

• 54:13Speaker 01

  Which I'd never have said, but then the university says, David, what the heck are you saying? It's like, so, you know, it's easier for me to not now talk to sensationalist media. And I've now, I'm much more comfortable doing this kind of thing where I can talk directly to the public.

• 54:29Rich Roll?

  Right.

• 54:30Speaker 01

  And I appreciate it.

• 54:30Rich Roll?

  Not getting misquoted.

• 54:31Speaker 01

  Yeah.

• 54:33Rich Roll?

  And how's the lab doing? Like, and how are the colleagues? Like, in the wake of the book's success, New York Times bestseller, like, you know, it's books everywhere, everywhere you look, I see it. You know, how are they kind of, you know,

• 54:48Rich Roll?

  acting towards you now?

• 54:50Speaker 01

  Uh, good.

• 54:50Rich Roll?

  Yeah.

• 54:51Speaker 01

  I've had no backlash about the book, which surprised me because of, it's a bold thing to say, maybe we figured this out. It upsets a lot of people, right? But um, as far as I know, they're not upset. In fact, I've had a lot of uh, praise from colleagues.

• 55:06Rich Roll?

  It's cool. The book is, um, I mean, congratulations. I think it's a, it's, I really think that it is um, a paradigm breaking master work. And what's, what's really interesting and unique about it, and, and I suspect, you know, sort of unexpected for somebody who's going to pick this up, is that, is that it's not just this hardcore scientific tome. It's sort of, you weave in a little memoir aspect to it. You tell these stories. There are incredible illustrations throughout. I know you won like an award for the illustrations, or the artist did. And you tell these amazing stories and you have these kind of poetic, you know, chapter titles. So it's a different experience than, than I was expecting, looking into it.

• 55:49Rich Roll?

  Like it's, it's, it's kind of genre bending in that regard.

• 55:54Speaker 01

  Well, thanks. Uh, I appreciate it. You know, anyone who knows me, I'm not, not really a scientist. I'm doing science because I have a, a goal in life. Like in high school, I was an artist and the, the, some of the illustrations at the back of the book, I drew myself, the headshots. So I'm an artist masquerading as a scientist. Um, but I think they go well together, actually. I'm, I think in terms of shapes and things moving around, I'm not um, so much a mathematician, mathematician. But that, that's why the book ended up being like that. I also have to give a big shout out to my co-author, Matt LaPlante, who took a whole bunch of crazy ideas that I had and synthesized them and wove them into this narrative, including some history, which I really believe that the best way to predict the future is to look back over the last 200 years to see where we're going.

• 56:37Speaker 01

  Especially also when you look at society, and there are a lot of things are said about the work that we're doing. Oh, we're all gonna run out of jobs. We're gonna have not enough food. What are we gonna do with all these people, of a population? If you look back at history. We've always been worried about that.

• 56:53Rich Roll?

  Right.

• 56:54Speaker 01

  And there are solutions. I mean, it's not all perfect. We can't have unlimited number of people on the planet. But that's why I wove history in there, because you you forget that people have gone through these kinds of things before and come out the other side much better. I don't think you'd want to go back to the 1840s with cholera rampant.

• 57:10Rich Roll?

  No. But we have our own particular set of problems now. And I do want to explore the kind of ethical and philosophical implications of your work. And I think a good kind of inroad into that is to start with Australia, right? You're Australian. Last time you were on the show, you told these amazing stories about your grandmother Vera wearing a bikini on Bondi Beach for the first time and just being this like, you know, I don't know, like, I just wish I had someone like her in my life. She just sounded amazing. And I can see how, you know, her influence on you has catalyzed this path that you've been on. But I spent, I just spent a month in Australia. I was there for all of December. I think you were probably there for part of that as well, right?

• 57:49Speaker 01

  Yeah, I think we probably overlapped.

• 57:51Rich Roll?

  Yeah. And and it was, it was quite something being in in Sydney amidst these fires. And it's, I know it's even worse right now in terms of air quality around that city. But it was relatively dystopian on days. People walking around with masks on, you really, you know, couldn't breathe the air. The sky was orange. The entire coastline, I mean, it's just the sheer scope of what's happening there right now is hard to imagine. I mean, I saw a news story this morning that said the smoke from the fires has actually circumnavigated the entire globe and is now back to Australia after going all the way around the planet.

• 58:32Speaker 01

  Yeah. Well, yeah, it definitely feels like Armageddon when you're there. And even I live in Boston, of course, and a few days ago, it was 70 degrees. You walk out there and you go, this is, this is craziness. You know, I grew up in Sydney, right on the bush, as I describe in the book. I almost had my house burnt down. Actually, last week, my brother's family lost a house. It was all burnt down. And there's nothing left except a bit of steel on the ground. Everything else just toasted. It it it it really brings home the fact that we are living in in dangerous times. And you can deny it, you can deny that the world isn't changing and we've lived through these times before. But let's let's just face it, let's use Occam's razor, the simplest explanation is that the world is fucking up and we are the cause of it.

• 59:16Speaker 01

  It's not that hard to admit unless you've got some other agenda. Uh, and Australia is a, you know, if you've never been to the Australian bush, you've got to realize this isn't like a forest with soil. This is tinder, this is the kind of leaves that if you put it in a fire, they explode. They're full of oils, eucalyptus oil mainly. And it's not hard to start a fire, a bit of a, you know, throw a cigarette out or whatever. Once it's going, this is basically a fire that you cannot put out because it's, it's not just going from leaf to leaf, it's going from tree to tree across the top. It's creating its own weather patterns. There was a couple of firemen were killed. Um, because the truck was caught in a tornado and blown on top of them.

• 59:59Rich Roll?

  Right.

• 1:00:00Speaker 01

  That's Armageddon kind of stuff. Um, and you go there and there's just this. I I think the Australians are in shock. Uh, when I was a kid, my house almost burnt down. I know what it's like to feel that your house has been burnt down. The problem that that I see now is that, you know, this is, this is not a one off. Fires in Australia normally start in around February. And, you know, we're in, we're in December or January. And this could be the new normal in California, right? Now it's, it's fires all year round, pretty much.

• 1:00:29Rich Roll?

  Yeah. And this fire in Australia has been going on for like four months at this point, right?

• 1:00:35Speaker 01

  Right, right. And.

• 1:00:36Rich Roll?

  I say fire singular, but it's a lot of different fires that are meeting up with each other, et cetera.

• 1:00:41Speaker 01

  Yeah. Yeah, it's a, it's a scary world and we we have to do something. And so what, so most people look at me and like, oh, David, you you study mice, what would you know about climate change? Uh, I have a conscience and I think about the impact of my research all the time. And what I've written about is that we need to mobilize resources on the planet. Billions, if not trillions of dollars to to tackle this, as well as other problems we have, like energy, resources, consumption. You've got to take money from somewhere to solve these problems. If they don't solve themselves. We can take it from the military, you could, there's opposition to that. You could take it from education, you don't want to do that. What about healthcare?

• 1:01:24Speaker 01

  Right now, we waste billions of dollars taking care of the elderly who don't need to be old. If if we're right and we do the kind of things that we talk about today as well as advances, we could have a world by the time we're elderly, where people in their eighties are just starting a new career like my dad did.

• 1:01:41Rich Roll?

  Yeah.

• 1:01:41Speaker 01

  That's a world where you a globe that would save trillions of dollars. Okay, so now it's easy to say you save trillion dollars, but that's money that can be poured into solving these problems. I like to think about Old London a lot because Old London in eighteen forty, the cholera thing that I then mentioned. People in the eighteen forties, they weren't solving the world's problems because they were too busy trying to figure out why everyone's dying. In a world where people are not dying and you're not taking care of them, then you've got the resources to solve these problems. And I don't know any other way besides stopping the military spending of getting a few trillion dollars to spend.

• 1:02:17Rich Roll?

  Yeah, I mean, the silver lining in what's happening in Australia is the opportunity that it will catalyze political will, right? And one of the things that was interesting when I was there is I didn't fully have have a sense of just how conservative the government is. And, you know, everything that's going on with the PM and he goes to Hawaii in the middle of all this on vacation. And, you know, the the impact of the coal industry on kind of, you know, the political perspective on what to do or not to do is all very interesting, right? So you're somebody who is incredibly optimistic about human ingenuity and, you know, excited about the potential of our species

• 1:02:59Rich Roll?

  to innovate our way out of any problem that we find ourselves in. And I can see that perspective and to some extent I can agree with that. But I think the limiters are really, you know, the governments and the politicians who are tied up in old systems that are holding us back and basically exacerbating the problems we're trying to solve.

• 1:03:18Speaker 01

  Yeah, no doubt, no doubt. And just to to hit the exclamation point, Old London, when they figured out that it was actually cholera from the water well.

• 1:03:31Speaker 01

  What Snow did was he removed the handle of the pump and cholera went away. But talk about politicians, what's not really known is that the politicians were under pressure because people didn't want to admit that the fecal-oral route of infection was true. They thought it was from the air. So they actually, the politicians, put the pump handle back on. And for another couple of years, there were still cholera plagues in London. So, you know, you talk about politicians screwing things up. I absolutely agree that if we can mobilize human ingenuity, we can solve anything. But we do a very bad job of that. I think where we are here in California is a hotspot for innovation, but most of the world doesn't really innovate.

• 1:04:12Rich Roll?

  Yeah, when we look at the state of healthcare in the United States, I mean, it's just, it's horrific compared to where it could be in terms of what we could be doing for people. And it's such a Byzantine mess, I don't see our way through it or out of it without some really significant changes at the highest level.

• 1:04:33Speaker 01

  Well, I agree with you, and that's one of the things that we're doing in the aging field is to talk to politicians as well as the FDA to convince them that aging is something that is important. Right now, if you talk to most doctors, even geriatricians who treat older people, aging is just the way it goes. We've got to deal with it, it's natural. Well, you know, when have we humans put up with what's natural if we didn't want to? Everything else we work on. Aging is one of these things, ooh, let's all live with it. But at the political level, I and my colleagues have talked to them, it's slow, you can't change the course of the Titanic too quickly. But we do see things bending and the FDA has actually agreed that if we do certain

• 1:05:15Speaker 01

  clinical trials, for instance, with metformin, the diabetes drug that we think might slow aging, if we can hit certain endpoints and show things are actually working, they are well-prepared to consider calling aging a treatable condition, if not a disease that we can prescribe medicines for.

• 1:05:32Rich Roll?

  Right. Yeah, I mean, the kind of underlying theme in the book and in your work is this idea that there is no biological law that we need to age, like we just sort of accept that as a truism, but in fact, you know, that doesn't necessarily hold water.

• 1:05:51Speaker 01

  No, no, nobody has any reason to say that that we have this clock that that cannot be changed. In fact, what we've learned, going back to the Horvath clock, is that about eighty percent of our lifestyle,

• 1:06:06Speaker 01

  eighty percent of our health in old age is due to our lifestyle and how we live.

• 1:06:09Rich Roll?

  Right.

• 1:06:10Speaker 01

  And only twenty percent is genetic. And actually, that's done by studying twins who, you know, some smoke, some don't.

• 1:06:17Rich Roll?

  Right, live different.

• 1:06:18Speaker 01

  Do all this stuff.

• 1:06:20Speaker 01

  Your genes are not your destiny. That's the good news. So that what that means is it's up to you. And if you want to be frail, or to be honest, dead at eighty, go for it. We know how to do that. Do everything that the marketing people want you to do. Eat the cake, sit on your fat ass and watch movies. That'll get you there pretty quickly.

• 1:06:41Rich Roll?

  Yeah.

• 1:06:41Speaker 01

  But fortunately, you know, in part, thanks to new media like this, we can actually all talk about what we think are the ways to extend lifespan and not be frail in old age. Like my father, I talk about him a lot. I'm very proud of him as a beacon of hope. At eighty, he's still running around like he's twenty five. He's got no aches or pains, very sharp minded, using all sorts of high tech, lifting more weights than I can, literally. And our trainer, who's currently training the two of us together, he says, you know what, I think my dad was deadlifting, or was it something like a hundred and eighty pounds, something a lot. And he said, the last eighty year old that I trained was was learning how to get out of a chair.

• 1:07:23Rich Roll?

  Right. Yeah, you you posted something on Instagram. He's like, you know, in the in the squat machine or whatever, like just killing it at eighty. The guy's in his second career. He's had this kind of,

• 1:07:36Rich Roll?

  you know, resurgence in vitality as a result of finding new purpose and meaning. And he's also somebody who's been on your kind of protocol for a while at this point. And to see him in the gym at eighty, like crushing it, it's very inspiring.

• 1:07:52Speaker 01

  Well, I think most of us can achieve that in life. You know, there will be unlucky people that, of course, diseases still will hit us. But most of us are wasting our our lives because we're we're basically not not you, but most people don't think about their longevity. They they think, oh, when I'm old, I'll deal with that when it comes. But now, in early and midlife is the time to invest because it'll pay off dividends later in life.

• 1:08:16Rich Roll?

  Mm hmm. We've done such a good job with medicine and pharma in increasing, I mean, you would probably disagree, but in increasing lifespan, but not so good in terms of increasing health span, right? Like, we now have to dodge all these bullets of modern life just to basically, you know, counteract that genetic marker to extend our vitality, right? Through the processed foods and the kind of, you know, luxury imperative that our culture, you know, reaffirms and enforces. Like, all of these things, we have to kind of opt out of of of the, you know, dominant paradigm in order to kind of thrive later in life.

• 1:08:57Speaker 01

  Yeah. Well, the dominant paradigm that's that's existed now for about 300 years is that doctors treat diseases. They don't treat lifestyle typically. There are exceptions, but mostly the doctors around where I work at these great hospitals, you they only see patients after they get sick. And so the the the aging process is already pretty advanced at that point. And aging is, let's not be be silly about it. Aging is what's driving cancer, heart disease, Alzheimer's. It's the main cause of disease and disability on this planet. It's not, I mean, the these diseases are real, but they're the endpoint of this process that we're working on. But most doctors don't think about aging.

• 1:09:40Speaker 01

  They don't think about what got people to the the cliff in the first place. And I call it whack-a-mole medicine, which is, and this is all great. I'm not criticizing my colleagues. We we do need medicines. We need to treat diseases, but it's a little too late for a lot of people. And this whack-a-mole medicine leads to the the paradigm of uh, come in with a disease, we'll treat it, hopefully fix it, kick you out the door, wait till you get sick again, come back and repeat until failure.

• 1:10:06Rich Roll?

  Mm hmm. Let's talk a little bit about the ethics of your work. So we were talking about Australia. You know, if we just look at what's happening there as a symbol of, you know, climate change in action and a kind of, you know, degraded planet Earth and a certain trajectory that we're on and have been on for some time. As somebody who, you know, by your own words said, you know, I'm concerned about the climate, just like everybody else, you have this mission to extend lifespan, which inevitably is going to lead to population growth, which is an exacerbant to the climate change problem that we're trying to solve. So let's kind of dig in to this and the implications

• 1:10:50Rich Roll?

  of like, let's say you're successful and your colleagues are successful and we get to a place where people can live to be 150, 175. People are, I would, I would imagine more likely to have more kids. There's more people on the planet. Suddenly we have to sustain a greater population and deal with these other problems that we so far to date haven't been so good at dealing with.

• 1:11:17Speaker 01

  So everything you said was right, except one thing. The healthier people are, the less kids they have later in life. So we can now extend the healthy period of life and we think, based on some animal studies, extend fertility. So women in the future will be able to have kids much later in life and have fewer of them. But let's look at the planet. We do have an issue on the planet. Of course, we've been going on exponential growth for the last couple of hundred years for our species, but it's, it's not the doomsday that we thought it was in the 1970s. Malthus and the erelics used to panic, make, make all of us panic because they said-

• 1:11:58Rich Roll?

  About global population growth.

• 1:11:59Speaker 01

  Well, about you're running out of resources. If you extrapolate this curve vertically, of course, we're all going to starve to death in the next 30 years. Actually, they thought by now we'd all be starving, to be fair. But what's happening is that what they didn't realize would happen, I think most of us didn't predict, is that as populations across the globe become healthier, they become wealthier. When they're wealthier, they become healthier.

• 1:12:25Speaker 01

  And then you lead, you have women who become educated.

• 1:12:29Rich Roll?

  Mm hmm.

• 1:12:29Speaker 01

  And women don't want to have fifteen kids. They don't want to always be pregnant. When you give them the choice, they have, you know, just a few. And what we're seeing is particularly in Africa, the rates of population growth are dramatically declining. I was just in Uganda late last year and I was talking to the locals and I said, you know, tell me about your family. Oh, my grandparents, fifteen kids or thirteen kids, I exaggerate. I have five brothers and sisters. What about you? Oh, we only want to have two because we want to give them an education. That's happening across the planet. So we're, you know, I'm drawing these curves. Anyone who's listening can't see this, but basically we're tapering off this exponential growth.

• 1:13:09Speaker 01

  We're going to max out according to the United Nations World Health Organization at about eleven billion. Now, that's still a lot of people, of course.

• 1:13:16Rich Roll?

  Max out on, on the resources.

• 1:13:19Speaker 01

  No, no, the number of people on the planet. So it's already tapering off and we're going to hit a sustainable level and actually start to decline in population based on projections.

• 1:13:29Rich Roll?

  Why wouldn't we just continue to populate until we blow through that ceiling?

• 1:13:33Speaker 01

  Well, because it, let's look at, even in the US, actually, population is going down and is barely at replacement level. In Western Europe, it's declining. Couples, on average, are having less than two kids. And there's plenty of people who choose not to have kids.

• 1:13:48Rich Roll?

  Yeah, I mean, this is one of Paul Hawken's big things when he, in his book Drawdown, one of the most powerful tools in the, the war against climate change or the, you know, the, the battle to solve this problem is educating girls. The more we can educate girls in, in the developing world, they're less likely to, you know, have as many kids, right?

• 1:14:09Speaker 01

  Exactly, exactly. So we're going to help build some schools over in Kenya that if anyone who can see this wristband, this reminds me every day, first of all, how lucky I am with my family here in the US. But also that there are people on the other side of the planet that, that need our help. But you're right, being a woman in, in these countries is the worst. There, if they don't have a well, they have to walk. You know, thanks to Justin Rennie's helping with the wells. Those things, giving them water, giving them education, that's part of the solution to the problem of overpopulation. And it doesn't initially make sense, but what you just said, Rich, is the most important thing. Give women the choice to decide how many kids they have.

• 1:14:48Rich Roll?

  Right.

• 1:14:51Rich Roll?

  Conversely, as a thought experiment, let's say you could live 200 years and a female's ability to reproduce extends way later into life. You can have these, you know, now it's sort of like you mature, you have kids and then you kind of, you know, gray into your older years, but you could get like two cracks at this, right? Like you could have kids and they grow up and you get older and then you get a new career and, you know, then you could just say, hey, let's do this again.

• 1:15:19Speaker 01

  Yeah.

• 1:15:19Rich Roll?

  Right?

• 1:15:20Speaker 01

  You, I'm sure there'll be people, and we know people like that. I won't name names, but I know a 98-year-old who has a kid who's in their 70s and also in their 20s.

• 1:15:32Speaker 01

  Anyway, I'm proud of him. He won't mind me mentioning his name, Norman Lear. He's fantastic.

• 1:15:36Rich Roll?

  Okay.

• 1:15:36Speaker 01

  Norm's one of those guys, but, but most people don't do that.

• 1:15:40Rich Roll?

  Yeah.

• 1:15:41Speaker 01

  But, but it's possible.

• 1:15:42Rich Roll?

  But what I'm saying is, when you're not just extending the number of years that you're running, you're extending your vitality into those years, right? So if you, if you remain vital later in life, like the idea of having a child at, at age 70, if you're operating the way you were when you were 40, seems like not such a bad idea.

• 1:16:01Speaker 01

  Thank you for saying that, because this isn't about science fiction, living to 170 and having, you know, a third of the world in wheelchairs. What we're talking about is real life. How much time do you want to spend with your parents before they get sick? How, or do you want them to, to spend another, you know, decade in a nursing home before they die? This is really personal. But it also, we've got to throw away our preconceptions of what being old is, right? We talk about Led Hamilton in his 50s, he's basically got the, the body and the looks of someone much, much younger. Being 50 is not old anymore. Certainly 60, even 80, like my father, that's not old anymore. If you take care of yourself. You extrapolate that into the future, there'll be a day when being 100 isn't old. You know,

• 1:16:46Speaker 01

  there'll still be people who don't take care of themselves and will be sick at 60. That'll always happen, but on average, people will continue to live longer. We've been on this trajectory of, of living healthier and being more youthful in our, our old age for the last few hundred years. And a child born today, if we stay on that trajectory, here in the US can expect, not just hope, but expect to live to 104. Okay? That means that they'll still be healthy 80 and 90, which is great. It's all about keeping people healthier for the longest period and then dying relatively quickly.

• 1:17:21Rich Roll?

  Yeah, when I was, you know, 10 years old, if there was a Laird Hamilton, a 55-year-old Laird Hamilton doing what he was doing, it would just be, it would have blown people's minds, right? I mean, not that he doesn't blow people's minds now, but that would just be the craziest thing you'd ever heard of.

• 1:17:36Speaker 01

  Exactly. So we live in a wonderful world where people can learn about things that typically they'd never read about, or maybe they'd have to wait 20 years. Right? My research, I'm talking about it as it happens, pretty much. It's a crazy world we live in, but it's wonderful. And also, young people now have access to information. You go back to when we were kids, how did we get information? Well, there was the local library, which was books that were basically old and musty. Or you could go to the World Book Encyclopedia or Encyclopedia Britannica and look up, you know, a paragraph of something. And this was all data and information that was old and not cutting edge. Today, you can learn about stuff that's happening and change your life based on things that we only dreamed about as kids.

• 1:18:21Rich Roll?

  Right.

• 1:18:30Rich Roll?

  From a philosophical perspective and like kind of playing on this thought experiment, like, let's say you could live 200, 300 years. How does that impact the psychology of a young person's mind in terms of how they make decisions about their career path or what they want their life to look like? And we did talk a little bit about this last time. But I'm interested in how that impacts like risk assessment, right? Like, if you're like, hey, man, I'm 18 and I'm going to live to 300, you know, barring me getting hit by a bus, like, you know, I have a lot of life to live. So am I really going to go skydiving?

• 1:19:13Rich Roll?

  Because then the risk of that seems so much more severe than it would if you're looking at, well, I'm going to only live to, you know, life's short and I'm going to die at 80 anyway. Like, I'm going to roll the dice and take these risks. And then how does that play out on a macro level in terms of what culture and society looks like?

• 1:19:30Speaker 01

  Yeah, well, we're already on that path. I don't think people in the 1840s and 50s were worried about bicycle helmets, if they had bicycles. You know what I mean? The longer we live, the healthier we are, the more protective we are of our bodies and our children. And that'll continue.

• 1:19:45Rich Roll?

  Right. Now that we're seeing a rubber banding with that, with like Jonathan Haidt and what he's doing in terms of like, you know, we need to rewild our kids because we're so worried about, we don't want them to go outside without a helmet on.

• 1:19:55Speaker 01

  Oh, it's extreme.

• 1:19:55Rich Roll?

  Walked around the street.

• 1:19:56Speaker 01

  It's extreme. I just got back from Shanghai where there are cameras that shame you on billboards if you cross the street when the lights are flashing.

• 1:20:03Rich Roll?

  Oh, really?

• 1:20:04Speaker 01

  The red, yeah. And it's, and it's got.

• 1:20:06Rich Roll?

  How does it shame you? Like a photo of your face?

• 1:20:09Speaker 01

  Yeah, right on the street. You can see the lady that crossed the street this morning that disobeyed the rules and she apparently.

• 1:20:15Rich Roll?

  Oh, my God.

• 1:20:16Speaker 01

  Has demerit points on her social, her social score.

• 1:20:19Rich Roll?

  Oh, that's just like, that's Black Mirror stuff right there.

• 1:20:22Speaker 01

  Yeah, scary stuff. Hopefully, this world that we live in won't be like that anytime soon. But yeah, the, the risks will, you don't want to take massive risks. But you know what? I think that we're, we're exaggerating. Maybe if we live for a million years, we're going to be a little bit more cautious crossing the street. But I think that if we live to 150, say, there are those of us who like taking risks anyway. I don't think somebody says, I'm going to wait till I'm 90 to jump out of an airplane. Do it when you're 20, right? So it's, there are risk takers and most of us will still take risks in life. You know, actually funny, funny aside is people think that I'm scared to die because I'm working on aging, but anyone who's seen me drive my car knows that that's not true. I'm a big risk taker, unfortunately.

• 1:21:07Rich Roll?

  On the road.

• 1:21:08Speaker 01

  I'm not, well, not anymore. I'm now a bit sedated, but I got, I shouldn't say sedated, but I'm, I'm more calm about my driving, but I do drive a fast car. I drive a Tesla and floor that, but.

• 1:21:23Speaker 01

  But I do like, I do like the feeling of risk. And it's the reason that I'm in this career in the first place. Cause I took a lot of risks when I was young to get here. Um, point being, you know, maybe I'll live to a hundred, maybe I'll live to a hundred fifty. I don't know, maybe I'll die tomorrow. I don't care. I, I like doing things that are novel. I like doing things that are risky. And I think that a lot of us will still do that, no matter how long we're gonna live. But I think the trend in, in the world is that the longer we live, the more scared we become of, of danger.

• 1:21:56Rich Roll?

  Right.

• 1:21:57Speaker 01

  Fireworks, are we gonna worry about fireworks? Yeah, that kind of thing. Um, but I'm not so worried. I think that these are small prices to pay for a world that is as different from today as we are from eighteen forty London.

• 1:22:12Rich Roll?

  Yeah. I think in tandem with trying to elongate life, lifespan and health span. You know, we also have to solve these other kind of, you know, cultural dilemmas that we find ourselves in that are contributing to mental decline and emotional decline. The disconnection, the, you know, addiction to technology, the, you know, lack of purpose that underscores most people's lives. And we talked about this last time too. Like, how does the, how does like the work of Dan Buettner and the Blue Zones kind of intersect with your own work? You know, ultimately, what's the point in living so long if, you know, our value system is, is, you know,

• 1:22:55Rich Roll?

  not in alignment with, you know, what's required to be fulfilled and to be happy and to have, you know, purpose for living that long?

• 1:23:04Speaker 01

  Yeah, a hundred percent. So there's the, there's the world of molecules and genes that, that I do for my day job. But I'm also very passionate about finding mission and purpose and doing the best you can in life. Cause that, that's also what I, what drives me. And so I, I think you're right, but if, if you're someone who's prone to depression, giving up, giving up hope, you gotta get out of that. You gotta find what excites you, what drives you. I teach a lot of students at Harvard and there are some students who are very smart, you know, some of the best, brightest in the world, but they're, they're, oh, I'm not sure I can do that, you know, whining around.

• 1:23:47Speaker 01

  I'm like, slap them around. Find a goal, go for it. This is your opportunity. And don't come to me with an experiment that'll advance science by one step. Come to me with, with an experiment or a question that'll advance us 20 years into the future. Now, that's not easy, right? That's the hardest part of science. The rest is just manipulating chemicals. Um, it's finding something that you wanna go for and change the world. And that's, that's what I think has been, if I have a secret to success, besides a lot of luck and hard work, it's at age four, having a goal and going for it.

• 1:24:24Rich Roll?

  Yeah, it is interesting that, that it dates all the way back. You know, your whole life has been infused with this, you know, this drive, this passion to, you know, solve this problem or, you know, basically advance humanity in this way.

• 1:24:38Speaker 01

  Well, you know, it makes a good story. And of course, looking back on it, it looks pretty easy. But there were, there still are plenty of times where I wonder, you know, do I really have to get out of bed today? This is tough, you know, ups and downs. And I say that because, uh, anyone who, who, who experiences this and has adversity, they have to know that that's part of the process. You don't grow, you don't learn, you don't succeed unless you go through that. And it never ends, right? I'm, I'm not riding high. I still have massive ups and downs and obstacles even at my age. Uh, but I've learned actually that if you have a goal, that's what gets you through it.

• 1:25:17Rich Roll?

  So when it's all said and done, like what is the, what is the legacy that you're working to leave behind? Like what, when you, when, when, when you're complete, what does it look like ideally?

• 1:25:29Speaker 01

  Uh, well, of course, that's never gonna happen.

• 1:25:33Rich Roll?

  But you hold this great vision. So what is that vision?

• 1:25:37Speaker 01

  Well, I would love to, to have a time machine to go a few hundred years into the future. And if I see a future where people are able to do multiple careers, you were talking about career arcs, I mean, what about a world where if, you know, not everyone can can have their dream job initially, I would love a world where people can live to one hundred and fifty, expect to be still playing tennis at one hundred and twenty. I think it's doable. There's no reason why we can't do that with our ingenuity. What that gives you is the time to have multiple careers, multiple lives, multiple partners, if you want, although you may find the right one in the beginning. But this is gives you, you

• 1:26:20Speaker 01

  know, let's, let's go back in time a little bit in eighteen forty. Okay, that person who's born in eighteen forty was not expecting to have, first of all, a great time at age forty or fifty. Basically, you're you're worn out by then. They don't expect to have multiple careers. They didn't have the opportunity anyway. So if you extrapolate from there to now and into the future just as much, what you have a world is where even if you you're dealt the wrong cards at the beginning of life, you have multiple chances to correct that. There are some risks to take, of course, and you do need some support. You know, I'm not running for president. I couldn't. I was born in the wrong country. But what I would love to have is what I call a skill battle, which is, well, it's another chance.

• 1:27:04Speaker 01

  It's if you're busting rocks or whatever it's that you hate, two years off, retrain, get another chance. And if you have a long life that's one hundred and fifty years long, you can do, you know, one career could last twenty, thirty years, become the best you can be at that, and then switch. And that that's a life that would be well lived, wouldn't it?

• 1:27:27Rich Roll?

  Yeah, I think it would. It would give people the patience that I think we lack right now. Like every, we're in such a hurry from the moment we're born, you know, it's a it's a habit trail of achievement and measuring ourselves against others. And, you know, from the moment you enter junior high school, and then it's grades in high school, and it's getting into like, you're, it's this race, right? And the brain And the emotional body isn't mature enough to really process that to make the best decisions. How are you supposed to, I mean, you knew what you wanted to do at a very young age. Most people don't, right? But they're kind of, you know, corralled into a certain path and on a trajectory that for a lot of people,

• 1:28:11Rich Roll?

  they don't, it's like a waking dream that they don't kind of come to out of until they're 40 and think, why am I even in this position? But if we could slow things down and say, hey, you're going to live to 150. No big rush here. Like, take your time, go on a kibbutz. You know, maybe there's a national, you know, sort of period of time where you're, you're, you know, of service or you do some kind of Teach for America, like programs like that that allow people to mature and develop the self-awareness and a sense of the world so that they can make that decision about how they can best contribute and find meaning and purpose in their lives, rather than being in such a rush.

• 1:28:54Speaker 01

  Yeah, I couldn't have said it better. You, you take someone like my father, who at 70 thought he had a few good years left. He'd be getting dementia by this point. He wasn't looking forward to the future. Late 70s is still perfectly fit. What am I going to do with my life? He started a new career.

• 1:29:09Rich Roll?

  Right.

• 1:29:10Speaker 01

  And so instead of being, you know, late part of your life, what's my legacy? We can turn that into, why don't I just begin a new one? And, you know, I'm now 50, you know what it's like. Normally, we should be, if anything was right, we look at our parents and their grandparents, their parents. 50 is the time when you're like, oh, I'm almost done. Wind down.

• 1:29:33Rich Roll?

  Right.

• 1:29:33Speaker 01

  It, that's not how the world is these days, and in the future it'll be even better. Where at 50, you're like, I'm just getting good at this. I just understand how the world works, although we never fully get it. I, I don't feel any different than I did when I was 30. I have a bit of more wisdom, of course, but everything else is the same physically, mentally.

• 1:29:50Rich Roll?

  And hopefully a greater appreciation for the wisdom of the elderly, rather than just warehousing them in nursing homes and trying to put them out of our line of sight and, you know, dismiss them, which is the tragic situation that we're in now.

• 1:30:06Speaker 01

  Yeah, it is. The older you get, actually, the more you appreciate these folks. What I want is a world where people in their 80s and 90s are not just appreciated, but they're actually utilized. If they're healthy, they can be advising or running companies or motivating the youth.

• 1:30:23Rich Roll?

  Right.

• 1:30:24Speaker 01

  That's the world that I want. Because once you're in a wheelchair or in a nursing home, then you're done for. And of course, young people are not going to want to spend their time listening to people who have dementia. But in a world where you can have a mentor who's seen 90 years of really interesting stuff, how cool is that?

• 1:30:41Rich Roll?

  The flip side of that is, and we touched on this last time, is the 120-year-old who's still on the Supreme Court and lacks the sort of plasticity to kind of adapt to, you know, modern times, who's stuck in an era that is bygone and thus is, despite their wisdom and experience of the ages, isn't in lockstep with what's actually happening. Right? I mean, that seems to be a potential downside to this.

• 1:31:07Speaker 01

  It's not perfect. It's not perfect. Right. There'll still be people who are in positions when they're too old to deal with the current.

• 1:31:13Rich Roll?

  But now it's like, finally, that, you know, these people are, we're getting rid of all these people so we can get fresh blood in here and a new perspective.

• 1:31:20Speaker 01

  I don't agree with that at all. I think that we should treasure those folks that have the wisdom and experience. Because history is really the way to predict the future, and they've seen it all, right? Someone like Warren Buffett, I mean, I would love to keep him around for a lot longer because someone like that, it does a lot of great things. But, you know, Bill Gates, same. There are people you want to keep around. Maybe there are few that we don't. But these are the prices to pay for a world where the majority of us can expect to be playing tennis on our 80th birthdays.

• 1:31:53Rich Roll?

  Right. As a result of doing this book tour, I would imagine you've probably met some pretty interesting people. I would imagine there's some pretty cool people reaching out to you.

• 1:32:04Speaker 01

  Yeah.

• 1:32:04Rich Roll?

  Yeah. You're gonna be cagey about this, right?

• 1:32:07Speaker 01

  Well, yeah, yeah.

• 1:32:08Rich Roll?

  I mean, it's, it's, you know, look, we all, you know, we all, we all wanna extend our lifespan. And this book has been very successful and you've been out talking about it. So I would imagine that that's created some interesting encounters for you.

• 1:32:23Speaker 01

  Yeah. Well, that's part of the joy that I have every day is I've learned that people are really interesting.

• 1:32:32Rich Roll?

  Yeah.

• 1:32:33Speaker 01

  As a teenager, I didn't go to medicine because I thought humans were the evil on the planet. I've kind of switched it around and realized that you can learn a lot just by listening. I'm talking today, but usually I'm quite, quite quiet. I don't name drop, but, but I've, I've met a lot of my idols in business, in Hollywood, a lot of billionaires. I've probably met a quarter of the world's billionaires at this point.

• 1:32:58Rich Roll?

  Yes.

• 1:32:59Speaker 01

  But there, I'm learning a lot.

• 1:33:00Rich Roll?

  You're the Ponce de Leon, right?

• 1:33:03Speaker 01

  Yeah. Well, you know, I, I am a spokesperson for this field. But I, I should say that there are hundreds of scientists like me, working away every day to help solve this problem.

• 1:33:17Rich Roll?

  Of course, the one thing that everyone wants to know and wants to talk to you about is, okay, you're the guy who's steeped in this, but like, what do you actually do? And what's interesting, you know, in, in hearing other interviews with you and the last time we spoke, et cetera. And in the book is that you're very quick to say and very certain to say, look, I'm not, I'm not a medical doctor and I'm not gonna, you know, give you a prescription for your life and I'm not gonna give you advice about, you know, certain protocols. And it's not until you get to the conclusion of the book where you actually say, actually here, but I will tell you a few things about what I do. And it's literally like a page in the entire book, right? So I'm interested in why you, because I would imagine in most interviews that this question gets asked, right?

• 1:34:01Rich Roll?

  This is what people, they're like, what do you do? Like, you're the one who knows more about this than almost anybody, so tell me what your habits are.

• 1:34:09Speaker 01

  Right. Well, I didn't, I didn't do it intentionally, but as it's worked out, worked out is that those who make it to the end of the book, get the reward.

• 1:34:16Rich Roll?

  Right. Okay, there it is.

• 1:34:17Speaker 01

  That's not why I did it. It's actually more that I'm in an unusual position, right? I'm a Harvard professor, I'm supposed to be world leading scientist and scientists are like monks. Monks don't go around telling people that, well, actually they do, but scientists shouldn't go around telling people how to live their lives. I'm, I'm part of this monastic group of people that are, should only say something if it's factual. Right?

• 1:34:47Rich Roll?

  Hmm.

• 1:34:48Speaker 01

  And I try my best to do that. The supplements that, that I admit that I take, uh, and that's rare for a scientist to admit that stuff, even though probably about half my colleagues are, are doing something. Um, I'm out on a limb. Um, now anyone who wants to jump to the page that Rich talked about is page three.

• 1:35:05Rich Roll?

  Page three oh four.

• 1:35:06Speaker 01

  Yeah, I get asked that a lot.

• 1:35:08Rich Roll?

  Oh, do you?

• 1:35:09Speaker 01

  Yeah.

• 1:35:09Rich Roll?

  That's so funny.

• 1:35:10Speaker 01

  But, but I've realized that, uh, there's a, a lot of demand for knowledge about this. And so what I've done is I've got a newsletter and so I'm updating people, people can subscribe if they'd like. It's at lifespanbook.com. And so I'm, I'm adding to the, those pages. Now, it's not just one page, to be fair, the, the whole of part two is about what you can do in terms of fasting and exercise and why it works.

• 1:35:36Rich Roll?

  Where you just kind of break it down and here are the things.

• 1:35:38Speaker 01

  Well, that this is, that's the cheat sheet.

• 1:35:39Rich Roll?

  Yeah.

• 1:35:40Speaker 01

  At the, uh, towards the end. Uh, but yeah, I, I can't run around saying, take this supplement or that brand is good. I will, first of all, I'll lose my credibility. I've got to be objective. Also, I don't spend my time testing products. That's not what I do. I'm a molecular biologist geneticist. Uh, but I'm, I am willing to go out on a limb and say what I do and what works and how I think you should, not should, but can adapt your life. The other thing that I hope everybody realizes is that what I do is a guide. It's not proven to work, but I've got, uh, the reason the book is full of references is if somebody wants to do a deep dive into a subject, whether it's fasting or the cold or sauna bathing

• 1:36:23Speaker 01

  or supplements, there's a lot of other. Scientific work that they can delve into as well.

• 1:36:30Rich Roll?

  Yeah, the notes, I mean, the notes go on for however many pages, three sixty. Yeah, so like fifty pages of notes at the end.

• 1:36:39Speaker 01

  Right. So, you know, I'm trained as a scientist and everything in that book was fact checked to the nth degree. And with references, and that's why when you read my book versus maybe some others that are that are not written by scientists. You can bet that what you're reading is factual as far as we know.

• 1:36:55Rich Roll?

  Well, let's talk about what it is that you do like let's in your estimation, like, what are the most important things that? And and again, you can preface this whatever with whatever caveats you want, but like, what do you think are the most important things that people should be? Doing or looking after on a daily basis to kind of, you know, take out an insurance policy against aging. Given the current state of knowledge and understanding.

• 1:37:19Speaker 01

  That's well put. Okay, now I feel free to speak because I don't endorse and I don't recommend.

• 1:37:26Speaker 01

  I think the most important thing for anybody to live healthier for longer. If there was just one thing I could say, it would be eat less often. Don't eat three meals a day. I I literally think that that people who recommend three meals plus snacks, trying to keep your glucose levels always at a pretty high level. Are doing the world a disservice. And I'm going to go out on a limb to say that a lot of nutritionists would disagree with me. But I've been doing this for thirty years. I've seen what happens to people and animals when you restrict their food. And it it's all good. I mean, you don't want malnutrition or starvation, of course. But putting the body in a state of want every day.

• 1:38:08Speaker 01

  For as long as you can do it, I do it, you know, like I said, hopefully till late afternoon dinner. That's the easiest and best thing you can do. Other things are the high intensity interval training or jumping up and down with weights in a swimming pool, almost drowning. That's pretty good.

• 1:38:22Rich Roll?

  Right. You're going back tomorrow, right?

• 1:38:24Speaker 01

  Yeah, well, I will do it again. Actually, now I'm I actually think I know not to go too far into the deep end.

• 1:38:32Speaker 01

  But but honestly, we now know we all have the the power with the scientific basis. To actually live at least fifteen years longer. Okay, so there are actually, and I I talked about this, I think, on Twitter recently. But there are there are five things that are pretty obvious and easy to do. Uh, that'll give you 15 years. And that's just off the top of, of my head. Things like, you know, exercise, the fasting, don't eat too much, eat the right foods, try to be uh, plant-based, uh, get sleep, have social network. That gives you 15 years. That's amazing. That's not even going, delving deep into my book, which takes it to another level of what the best

• 1:39:16Speaker 01

  exercise and supplements probably are. So that's the good news. Um, I do list a lot of things. We could, we could talk for hours about what I do. Page three hundred and four, you'll see more. Um, I'm conscious that we have a microbiome that is, that needs to be healthy. So I make my own special uh, yogurt, which I mix my resveratrol in. Um, I think I'll, I'll release the recipe of that pretty soon to the, in the newsletter, if anyone would like to make it. So that, these are the things. Um.

• 1:39:46Rich Roll?

  On the, uh, sorry to interject, but on the, you, you sure sort of said, you know, eating, eating plant-based, predominantly plant-based. I mean, a lot of that is, is um, informed by the relationship between excessive protein intake and that, the, that impact on aging, correct?

• 1:40:07Speaker 01

  Well, it's both.

• 1:40:07Rich Roll?

  From your, from your perspective in the work that you're doing.

• 1:40:10Speaker 01

  Right, right. Fair enough. So there, there, there are at least a couple of things to talk about. One is, so Dan Buten is right, and I have a lot of good friends that study populations that live a long time. I think that's a very good guide as to what we should do. It's eat plants that are full of polyphenols that are stressed out. And this is what the Okinawans and the Sardinians do. Makes a lot of sense. They're activating longevity genes. So the plant-based food, um, I think a little bit of meat's fine, especially if you work out and you're trying to do bulk up, bulk up some muscle. But I think that what we've learned is by studying the Sardinians and Okinawans, is that those diets are the best for, for humans. And they are mostly plant-based with a little bit of meat like fish. So why does that work? Okay. Why, why do we think

• 1:40:54Speaker 01

  that works? The two reasons. One is that you don't want to overload on some types of amino acids, which you'll find in meat, uh, leucine, isoleucine, valine, these are. Turn off our body's defenses through a pathway called mTOR. There'll probably be a Nobel Prize awarded for that stuff, by the way. It's a big deal, mTOR. But if you're always eating a lot of protein in terms of meat, then you'll never really optimize your body's defenses. So I try to eat plant-based foods. But there's another thing that that most people miss, which is the xenohormetic molecules from plants. You get those, you don't get those from meat as much.

• 1:41:33Rich Roll?

  So what do you make of the carnivore diet?

• 1:41:36Speaker 01

  Yeah, I'm on the other side.

• 1:41:40Rich Roll?

  It is an interesting phenomenon, just like sort of culturally to go, how did this suddenly happen? And there's a cohort of people who are all about just, that's all they eat, right? This hasn't been going on for very long. The story very much has yet to be fully told. But, you know, if somebody's listening to this and perhaps was flirting with the idea of that, I mean, you know, what would be your response to that person?

• 1:42:06Speaker 01

  All right, well, so I'm a scientist, so let's talk some science briefly. What you do when you activate this mTOR pathway is you're telling your cells in your body that times are good. You've just caught a mammoth, okay, basically. And now's the time to build your body and actually fix things, heal things and grow. And it turns out that there are two things your body can do. There's grow, and then there's, on the other hand, the other side of the balance is to protect. Growth, protect, growth, protect. And if you're always in this growth mode by telling your body, now's the time you got your amino acids, grow.

• 1:42:49Speaker 01

  That's great when you're young and middle-aged, you'll bulk up, right? You'll feel good, you'll actually burn energy more, you'll lose a bit of fat.

• 1:42:58Speaker 01

  But long term, you're going to sacrifice your longevity, in my view, because you're not turning on your body's defenses, which typically are turned on when your body senses that there's adversity.

• 1:43:08Rich Roll?

  There's a need.

• 1:43:09Speaker 01

  Yeah. So being hungry and eating plants are going to be telling your body, times are not as good. We've run out of mammoth meat. Let's hunker down.

• 1:43:19Rich Roll?

  But you could We're on our own. We're on our own. So we're going to have to, you know, do the heavy lifting here. It's it's basically catalyzing these systems, these biological systems to protect the body. Right?

• 1:43:32Speaker 01

  Yeah.

• 1:43:32Rich Roll?

  And and in turn promote longevity versus, oh, this, we got an endless supply of food coming in here. We can just shut everything down because we don't have to worry about it.

• 1:43:41Speaker 01

  Right. Think of it this way. When we're young, our defenses are on hyper alert. Our bodies don't get diseases. You don't find babies with Alzheimer's disease. Their cells know how to repair and and defend against issues.

• 1:43:55Speaker 01

  By eating a lot of meat, I think what you'd likely to be doing is accelerating that process towards older age. So because your your body will, yeah, be in a growth state, but you won't be turning on your body's defenses. And actually, as you get older, your defenses go down and down and down. And that's one of the main reasons that we end up getting old.

• 1:44:16Rich Roll?

  Right.

• 1:44:16Speaker 01

  Okay. So you've got to get your defenses up like you're a baby. Speaking of which, I've been on on a much healthier diet the last few years, including intermittent fasting, including the supplements that I've got written on page three hundred and four. One of the people say, oh, I'm not noticing anything after, you know, maybe two weeks on the on supplement. Of course, you're not going to see that. I've been doing it for some of them for 10 years. But what I've noticed most recently with my current lifestyle, all of these things combined, the biggest things that that has changed for me is that I don't get sick anymore. That's amazing. I used to be the kind of guy that would go from one cold to another. I haven't had a sniffle in years. I can't remember the last time I had a cold. And I'm on planes. People are sneezing on me. I'm shaking hands with people pretty much all the time.

• 1:45:02Speaker 01

  So my immune system must be on hyper alert. And why is that good?

• 1:45:08Speaker 01

  If you ask a centenarian, what about your younger years in your 50s, 60s? They'll say, I never got sick, never got a cold.

• 1:45:15Rich Roll?

  Mm hmm.

• 1:45:16Speaker 01

  My father's like that. He doesn't get colds even.

• 1:45:18Rich Roll?

  Yeah. What about sleep? Have you looked at the impact of sleep on all of this?

• 1:45:24Speaker 01

  Some people have. Uh, well, we've done a little bit in mice. What we've discovered is that the sort of twines that we work on, these protectors that respond to the NAD levels in our body, they cycle through the day and they're actually controlling our sleep wake cycle. That's really fascinating because what it means is that longevity protectors, these adversity sensing genes are also controlling our body's clock.

• 1:45:51Rich Roll?

  Uh huh.

• 1:45:51Speaker 01

  And if you're screwing up your longevity defenses, you're also probably screwing up your body's clock.

• 1:45:56Rich Roll?

  Yeah.

• 1:45:57Speaker 01

  So another side effect that I get with this new lifestyle is I get much better sleep. And I know that, um, you know, we've got rings that can tell us that now. And I feel great. I don't wake up tired anymore. The, so this NAMPT gene we talked about earlier, the one that makes NAD, that's actually going up and down in levels throughout the day. It goes up in the morning, down. It's changing the NAD levels. And, uh, and if you get that out of whack, we get this thing we call jet lag.

• 1:46:27Rich Roll?

  Mm hmm.

• 1:46:28Speaker 01

  And another side effect, actually, I find it anecdotally, it's not proven, is that if I raise my NAD levels either by fasting, exercising or taking a supplement, I don't get the effects of jet lag.

• 1:46:40Rich Roll?

  That's interesting. Wow. That's super interesting. Um, all right. So fasting, trying to, uh, create some hormesis in your life, uh, basically living a blue zones lifestyle. Um, in terms of supplementation, you're, I know you're not going to give like. You know, specific recommendations, but basically, walking through what you do, you take a daily resveratrol, you take an NMN supplement, which is basically a supplement oriented around promoting NAD, correct?

• 1:47:16Speaker 01

  Correct.

• 1:47:17Rich Roll?

  A different version of that would be NR, right? Which is like one step removed from that same process?

• 1:47:22Speaker 01

  Yeah, so the body uses NR, which is short for nicotinamide riboside. It'll convert NR into NMN, and then NMN into NAD. And that last step, uh, no, that first step is this NAMP T gene. Okay, so yeah, you can, people are taking NR, or they're taking NMN. NR is a little cheaper than NMN. Uh, I've studied NMN, people ask me, why not NR? Well, NMN, first of all, is more stable on the shelf, so that's good. But also, uh, I find that, um, it produces some better effects in mice, when, say, for endurance. But, uh, the truth is, even though there's a lot of chatter on the internet, and some of my colleagues

• 1:48:03Speaker 01

  have their stakes in some companies, I, by the way, I don't benefit from any supplements ever. So I have no stake in this. Uh, but my, some of my colleagues and on the internet, they're saying, oh, one is better than the other. The truth is, we really don't know yet which is better, or if it, if they're the same. Uh, I, I take NMN because, A, I have a ready supply, because we're doing clinical trials, but also, uh, because I've studied it the most.

• 1:48:28Rich Roll?

  And that's it, right? There's no other, are you, is there anything else that you're taking?

• 1:48:33Speaker 01

  Yeah, yeah, there's a, there's a bit of a list. Uh, I'm also taking a drug. Ooh, a drug, right? Uh, a drug called Metformin, which is the diabetes drug, yeah. Um, so Metformin has been around since the 1970s, and been in tens of millions of people. It's relatively safe, it's not perfect, it's not totally risk-free. But most people, what they experience is an upset stomach and a lack of appetite, uh, which can be mitigated by a slow-release tablet. You do need a doctor's prescription in the US to get it, or in Canada, or in Australia, or the UK. Uh, other parts of the world, uh, you can just go buy it at a pharmacy, because it's on the list of the World Health Organization's list of essential medicines for humanity.

• 1:49:13Rich Roll?

  So what prompted you to get on Metformin?

• 1:49:17Speaker 01

  Oh yeah, really simple. Um, my best friend told me to, uh, to take it. No, but, uh, in all seriousness, so his name's Neor Barzalay, he's considered the world's expert in this. But, you know, I don't just do what my friends say. I have to research this. So I looked at the literature and there are a couple of studies that I cite in the book. They're worth reading. Don't just take my word for it. If you look at over a hundred thousand people, in some cases, they're veterans, but mostly older people, um, of, of all walks of life who have taken Metformin because of their type two diabetes, high blood sugar. If you look at other diseases over the next, I think it's five years time, those that have a high risk of Alzheimer's who don't take

• 1:49:58Speaker 01

  Metformin have a much higher risk of Alzheimer's than those that took Metformin. And the same is true for some cancers and frailty, um, and heart disease.

• 1:50:09Rich Roll?

  So what is that interplay? Like, why would that be the case?

• 1:50:13Speaker 01

  Right. Well, there's a lot of debate about how Metformin works. The, the main explanation is that there's an enzyme called AMPK or AMP kinase that talk to the sirtuins. So they're actually into play and actually mTOR. So there are three main anti-aging pathways. I've talked about sirtuins that we worked on in yeast and now in mammals. The middle one is the AMPK, which Metformin works on. And then this mTOR, which responds to low amounts of protein. And they all talk to each other. So we used to fight as scientists, my pathway is more important than your pathway, blah, blah, blah. And it was vicious. People were trying to kill each other. Now we realize that there's a network and if you tweak one, you can tweak the, you'll tweak the other. But I think what the best is to, to tweak them both, just at moderate levels and get

• 1:50:58Speaker 01

  the best. Anyway, AMPK, what it does to the body is it, for one thing, main thing is it ramps up energy production, mitochondrial activity, it's called. And mitochondria, most people, uh, may have heard are the battery packs of the cell. And the more you exercise, and if you fast, calorie restrict, you'll have more mitochondria. That's a good thing. That as far as I know, there's, you can't have too many mitochondria.

• 1:51:23Rich Roll?

  That's the key to being a, a good endurance athlete, mitochondrial density.

• 1:51:28Speaker 01

  It is, it really is. And actually, as we get older, uh, we lose about half of our mitochondria. Um, but one way to boost that is to take metformin or to, uh, to do these other things like exercise. But it's not all good news. Um, there are some studies that show that metformin can interfere with endurance and muscle. Um, hypertrophy. Uh, and there's been a lot of talk about it, actually, on the internet. Peter Attia has done some, some work, uh, podcasts on this. Neo Barzalai, my good friend at Albert Einstein College of Medicine, was on that study. So I, I called him up and I said, what's the skinny on this? Tell me. And he said, it's overblown. And so when you look at the data, um, and I'm, I'm going to be using my hands for graphs, but basically

• 1:52:11Speaker 01

  the, the, the two bar graphs are overlapping. There's some minor differences, but there are plenty of people in that study that took metformin that gained more muscle than those that didn't. But overall, on average, there was a slight, very slight, uh, increase in muscle mass in those that weren't taking metformin and doing weights. But there were benefits to the metformin. There was lower inflammation, lower oxidative stress in the people that took the drug. So what do I think is the take home message? Number one, don't panic. If you're an average person, if you don't make a living from bodybuilding, it's not going to matter that much. But in an abundance of caution, what I do is I don't take metformin on days I work out.

• 1:52:52Speaker 01

  Pretty simple solution. Um, but I still think on days where I'm not working out, metformin is going to protect me against these major diseases.

• 1:53:01Rich Roll?

  So your impetus to get on metformin didn't have to do with elevated blood glucose or, or insulin resistance? It was pure, it was more from this sort of longevity, self experiment perspective?

• 1:53:14Speaker 01

  Well, it's both. You know, there's, there's never one answer to these things. My father and his father were, and myself, were, were susceptible to obesity and diabetes. I'd be, I'd be twice my weight if I ate what I felt like eating. And my son struggles with this a lot. He's 12 and already struggling. So we've got obesity genes and my father went on metformin years ago, and I think is one of the reasons he's probably still healthy. So that's that's also a factor, no question that I took that into account. I didn't take metformin um before I got diabetes until recently. Uh, because I just wasn't sure it was worth the risk versus the reward. But when I dug into the science of this, it was a no brainer. The risk for me is very low.

• 1:53:58Speaker 01

  The worst that I get is an upset stomach and actually I I feel less hungry. So that's a side effect that I like. And then on the upside is some of the chances of getting. Uh, I forget which type of cancer, but it's in the book uh can be lowered by forty percent. That that's a massive, massive effect. So you you always got to balance it. So I don't prescribe anything to people, but what I would recommend to do is to think. Um, what risk am I willing to take? Uh, what are the potential downsides? And with a drug that's been in millions of people, there's a risk, but it the risk is pretty low. Um, how old am I? You know, if I if I'm a hundred and ten, I've probably only got two more years. So what what's there to lose? So that's obviously a calculation.

• 1:54:42Speaker 01

  Um, and then, uh, you know, how expensive is it, right? Some some of these things are still just very new to the market. And all of that has led to me uh adapting my life over the years. Admittedly, some of these discoveries are fairly new, so I haven't been doing them longer than. I I would have preferred to have done them earlier. Um, but that's the calculation. And so I I think that we all know what's going to happen in the end if we don't do anything. If we just sit around and do what, you know, we we think feels comfortable. The end is not pretty. I've seen what happens. Um, the other thing that that I want to talk about or just mention at least is is smoking. So my mother died of lung cancer. It was brutal to see her pass away.

• 1:55:27Rich Roll?

  She had a lung removed, right?

• 1:55:28Speaker 01

  She did, and then her final lung gave out twenty years later.

• 1:55:31Rich Roll?

  Um, so she lived for twenty years on one lung?

• 1:55:35Speaker 01

  She did.

• 1:55:36Rich Roll?

  Wow.

• 1:55:36Speaker 01

  She managed to live a pretty good life. Uh, she visited about eighteen countries after that. But the way that she passed away, I don't know, have you ever seen someone die?

• 1:55:48Rich Roll?

  Hmm, no, uh, not in that way.

• 1:55:50Speaker 01

  Yeah, I've never seen someone die except for my mother. Uh, but she basically was drowning in her own fluid. And it happened pretty quickly, so all I had a chance to do was to whisper in her ear while she was choking to death, that I wanted to thank her for being the best mother I could ever hope for. Now, a lot of people die like that. Do not smoke. If you smoke, please, please try to give up because it's not pretty. And not only are you increasing your chance of lung cancer, smoking will age you. We know that that clock, the Horvath clock, is accelerated by smoking because it's damaging the DNA and distracting the pianist.

• 1:56:28Rich Roll?

  Yeah.

• 1:56:30Rich Roll?

  If you could, what is, what's the study that you would like to see perform? Like if you could design, you know, the perfect human trial, for example, where you could do whatever you want, uh, what would that look like and what would you hope to establish?

• 1:56:47Speaker 01

  Well, I don't have to imagine that. We've designed one. Well, so I mentioned Neer again, Neer Barzalay. He and a number of scientists have devised a study that the FDA has approved as being reasonable test of whether you can slow aging down. It's going to involve hundreds of people and a few hospitals around the country. It's called T A M E or TAME. What is a targeting aging with metformin, something. Anyway, so that's getting underway. That I think is a very good start. The idea is to take people who are elderly, who are not yet sick, and monitor them over a period of five years and test their frailty and their susceptibility to diseases.

• 1:57:30Speaker 01

  And if we're right, we'll be able to show with those numbers of people that A, their clock is slowed down, but B, that they remain healthier because of, in this case, metformin. But, you know, if I had a billion dollars, I'd take the top 15 drugs or molecules or supplements and test those as well. Because otherwise, all we're left with is, you know, what we're doing, just trying to figure this out ourselves.

• 1:57:56Rich Roll?

  And what's going on in your lab right now? Like when you go back home, what are you working on?

• 1:58:00Speaker 01

  It's pretty darn exciting. I gotta say, I'm very privileged to run a lab. There are good days and bad days, but most good days are my students are every few days coming to me saying, it's finally worked. We've had a breakthrough. So for instance, we've had this breakthrough in reducing the cost of this clock. Maybe we'll bring it down to five bucks. That's a great breakthrough. That keeps me happy.

• 1:58:24Speaker 01

  The big thing is reprogramming. We've now gone from slowing down aging with resveratrol and NAD boosters, reversing some aspects of aging like endurance in mice and hopefully people. But the big thing that's just happened over the last couple of years in the lab and increasingly excitingly in the lab is the ability to replace the pianist that's gone demented and reset the clock and get it to go backwards. So we've put this paper online and anybody in anywhere in the world can look at it. If you'd like, you can go to a place called BioArchive, B I O R X I V. Okay. If you type in reprogramming and my name Sinclair, you'll probably find it too.

• 1:59:09Rich Roll?

  We'll link it up in the show notes.

• 1:59:10Speaker 01

  Great. So we're very proud of that, that paper, which is still under review. So it hasn't hit the media. Actually, I gotta say, I know I'm rambling here, but podcasts are a fantastic way of getting news out before the actual news. People find it out. So you're hearing it here first, but we hope that by sometime early this year, maybe by June, we'll have this published. We were revising it for the journal Nature, which is one of the top in the world. We're excited that we got good reviews from our colleagues who do blind or anonymous peer review. That's a long way of saying we are pushing the boundary of this reprogramming method. Just to quickly.

• 1:59:48Rich Roll?

  And the abstract of that study is what? Yeah.

• 1:59:50Speaker 01

  Yeah. Yeah. So the summary is that those methyl groups that are counting that we use to count the clock. Uh, we can tell the cell to remove the right ones so that they, that the cell remembers how to play its genome correctly, like it was young. There are three genes that we, we take from, um, out of the book of embryo. So when you're an embryo, you're using three particular genes to, to grow and be healthy. They get switched off by the time we're young adults, uh, even while we're babies. If you put them back in just at the right time, the right place, at the right, uh, moment. We found that it's, it's, we don't see any safety issues. So that's the good thing. But what we see is the clock gets wound backwards.

• 2:00:33Speaker 01

  Those methyl groups go back. Long story short, the cells are reprogrammed to be young again, completely. Not just a little bit, not two percent, not two years. But we can take it, for example, in this paper, you'll see, if you, if anyone looks at it, you can take mice that have gone blind from old age. If we put these three genes into the eye and turn them on for a few weeks, their vision comes back as though they were young again. What that tells me is that a lot of what we regard as a one-way street in aging is reversible. If we can restore eyesight, what else can we reverse?

• 2:01:10Rich Roll?

  I mean, that's gotta be about as exciting as it gets, right?

• 2:01:14Speaker 01

  Yeah, I've seen a lot. This is pretty amazing. Wow. And, and our colleagues, and I have to credit, we have a lot of help. I don't know my way around a mouse as I, to save my life, but our colleagues that did these experiments with us, they're blown away. My colleague, Bruce Cassandra at Mass Eye and Ear Hospital in Boston, he called me up at 10:30 at night and he said, David, you wouldn't believe what we've just seen. Uh, excuse the pun. We've got restoration of vision. I want to run down tomorrow and tell the FDA this is possible. Cause right now, degenerative eye diseases like glaucoma, macular degeneration, these are not reversible. The best you can do is slow them down slightly. Anyway, that, that's a whole story, but what we're now trying to figure out in my lab is how is it possible to reset the cell? How does that work?

• 2:01:58Speaker 01

  And where is the reset switch? What, what's the repository of the information? Put another way, where's the backup hard drive of the cell?

• 2:02:07Rich Roll?

  Right. So when that analog system gets scratched, there's an ability to reboot it with, you know, a digital replicant that is perfect.

• 2:02:18Speaker 01

  Yeah. And we don't know where that information resides. We know we can tap into it by using these three genes called O, S and K for short. But how that works and where it goes to find the old information to be young, it could be a chemical on the DNA. It could be a protein that sticks to DNA for our whole lives. We're actively searching. And so we've got a whole bunch of very smart people in my lab look working hard on that.

• 2:02:42Rich Roll?

  And obviously, you know, human beings are infinitely more complex than mice. But what can you extrapolate from that to give you confidence about applicability in, in, in a human context?

• 2:02:55Speaker 01

  Right. Well, we, we, we don't know, but we, we do work in human cells. So we can take human neurons and grow them, make a mini brain in the dish. And we can both accelerate aging, make the pianist demented in those cells, and we can reverse the age of those cells and make them grow again, like they were young. So we've done it, what we say in vitro, in the dish. We've done it in mice. Our eyes and our biological systems aren't any different than a mouse's really. So I'm optimistic, you know, but until we know in humans that we can do this, I can't declare victory. So what I'm doing, as I typically do is try to spin out the technology, get it into patients as safely and as fast as

• 2:03:40Speaker 01

  possible. But in, hopefully in the next few years, we'll have the first patient tested and the results will be pretty quick. This isn't like a long-term longevity study. If we can restore vision to a patient with glaucoma, we should know within a few weeks.

• 2:03:55Rich Roll?

  And I would imagine that, I mean, basically you're dealing with a reversal mechanism. So there's no reason to believe that it would only be operational in, you know, in, in the optic context. Like it should, it should be applicable across the board or in other, you know, with respect to other problems.

• 2:04:12Speaker 01

  You are exactly right. We didn't choose the eye because it was easy. We chose it because it was hard. And because the eye gets old very quickly. If you damage your eyes, it's not going to grow back like your skin. So we thought, let's go for it. My student, Wan Chang Lu is, is a brave, brave student. So if we can do that to the eye, I'm much more optimistic that these other organs and systems, whether it be a kidney that's failing, or a liver, skin, who knows, we're going to test that rigorously. We can even try to reprogram the entire animal. We've started doing that.

• 2:04:46Rich Roll?

  Now you're just getting crazy, right?

• 2:04:49Speaker 01

  Well, you gotta do it. I'm sure everyone else wants to know the answer. But here's what's holding us back in the technology. The ability to deliver genes is not as easy as everyone thinks it is. Right now, there are some drugs on the market that can actually fix genetic diseases in blood and in the eye. But trying to get gene therapy to the rest of the body is still a challenge. And so one of the things we're working on, and having some success is being able to deliver it to every cell in the body, or nearly every cell in the body, and not have it all concentrated in the liver, which is typically where these genes go when you deliver them IV. But ultimately, imagine a world, let's be a little bit of

• 2:05:33Speaker 01

  dreamers here, if my colleagues will allow me. Imagine a world where you have these three genes put into your body, let's say at 50, and then you're basically like Deadpool. If you get injured, you can have an IV, turn on these genes, heal better. You lose your eyesight, turn it on in the eye, fix your eye, who knows what, have an IV, whole body rejuvenation, that would be pretty interesting. And we've only reset aging once in the eye. We don't know if you can do it twice, we don't know if you can do it 10 times, or infinitely.

• 2:06:09Rich Roll?

  Well, more will be revealed.

• 2:06:11Speaker 01

  We will come back. I'll come back and tell you how things are going.

• 2:06:13Rich Roll?

  Yeah, please do. We're all counting on you. You have the civilization rests on your shoulders, the future of all of us.

• 2:06:21Speaker 01

  Well, and in the meantime,

• 2:06:22Rich Roll?

  In the seat of your lab.

• 2:06:23Speaker 01

  There's a lot we can do to stay healthy for longer. And actually, every year you're alive, you get an extra three months of life, because technology is changing.

• 2:06:31Rich Roll?

  That's encouraging. That's gonna, that's gonna like allow us to end this on an optimistic note, I think. Thank you. Super interesting. I really have so much respect for the work that you're doing. You did a beautiful job with this book. There's so much to learn, and I know that you're at the cutting edge of, of learning it for all of us. So come back and keep us up to date on everything that's going on.

• 2:06:56Speaker 01

  I'd love to.

• 2:06:57Rich Roll?

  Yeah, thank you so much. Pick up the book Lifespan. Support local booksellers. If you can't find it at your local bookseller, tell them to order it for you, or go to Amazon.

• 2:07:08Speaker 01

  Yeah, wherever good books are sold.

• 2:07:10Rich Roll?

  And David is easy to find on the internet. It's just @DavidSinclairPhD on Instagram.

• 2:07:17Speaker 01

  Yeah, Twitter is David A. Sinclair.

• 2:07:21Rich Roll?

  Cool. Awesome, man. Anything else you want to let people know about before we end it here?

• 2:07:25Speaker 01

  Let's all celebrate 80 years from now.

• 2:07:29Rich Roll?

  That sounds good, man. It's a plan. Where's the party gonna be? Your house?

• 2:07:33Speaker 01

  I think we'll do it at your house.

• 2:07:34Rich Roll?

  All right, good. Thank you, man. Talk to you soon.

• 2:07:36Speaker 01

  Peace.

• 2:07:40Rich Roll?

  Brilliant mind, lovely human, that David Sinclair. I really enjoyed that. Bit of a mind blower. Do me a favor. Let David know how this one landed for you. You can hit him up on Twitter @DavidAsinclair, or on Instagram @DavidSinclairPhD. Don't forget to pick up a copy of his new book, Lifespan: The Revolutionary Science of Why We Age and Why We Don't Have To. I think you guys are gonna really enjoy that. And as always, be sure to check out the show notes on the episode page at richroll.com to dig deeper into David's world and work. If you'd like to support the show, there are many ways to do that. Subscribe, rate, and comment on the program on Apple Podcasts, or on Spotify for all you Android users. And of course, subscribe to our YouTube channel where we are sharing

• 2:08:25Rich Roll?

  All of this content in a visual manner. Share the show or your favorite episodes with friends or on social media. I love seeing all the screen grabs on Instagram. And as always, you can support us on Patreon at ritual.com/donate. I appreciate my team that works hard and deliberately on this show every week. Jason Camiolo for audio engineering, production, show notes and interstitial music. Blake Curtis and Margot Lubin for video. Jessica Miranda for graphics. Ally Rogers for portraits. Georgia Whaley for copywriting. DK for advertiser relationships and theme music as always by Analemma. Appreciate the love, you guys. See you back here next week with another PhD Cyrus Kombata along with Robbie Babaro

• 2:09:04Rich Roll?

  to discuss all things diabetes, including some pretty incredible stuff about this devastating illness, how it can be prevented, treated, and in many cases reversed. I think you guys are going to really enjoy it. I think it's going to really surprise you. And here is a clip to take you out. Until then, peace, plants, namaste.

• 2:09:27Speaker 02

  I think part of the problem here is that doctors are not trained in nutrition, first of all. So they go through medical school. You know, they go through four years of medical school, plus a residency, plus a fellowship. Sometimes that can be almost a decade worth of schooling. And you ask your average doctor, hey, how much nutrition do you learn? And they're like, eh, I don't know. I learned one class, one day, maybe six hours. Right? And there's studies that actually show that the average doctor learns nutrition for a maximum of 20 to 25 hours while they're in med school. So they're just not given the training to talk about food. And it's not their fault because doctors are phenomenal human beings and they go into it with altruistic tendencies, but they're just not given the right toolset. So they leave medical school, they go into their practice. And then when they, when somebody with diabetes or high cholesterol or hypertension presents

• 2:10:09Speaker 02

  to them, their solution is like, well, I have this pill that I, you know, can prescribe for you because that's the system that I know how to do.

• 2:10:17Speaker 03

  And that's part of the confusion around diabetes. It's one of the few chronic conditions you can monitor on a meal by meal basis. You can look at your own glucose meter.

• 2:10:26Rich Roll?

  Constantly getting feedback all day long.

• 2:10:27Speaker 03

  Right. And, and like you said, we're going to get into the weeds on, you know, the, the cause and what's going on here. But yes, there is particular confusion in diabetes that is very nuanced. And that is part of the reason I think this approach has not caught on yet because people don't understand the confusion of the headlines and the studies that are being cited, just a lot of misinformation. The disconnect between the research and what the public believes and understands is mind-boggling. It's massive. Absolutely mind-boggling.