The Rich Roll Podcast - Rewind Your Clock: David Sinclair, PhD Wants To 'Cure' Aging

Episode Date: February 10, 2020

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

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. 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. That's David Sinclair, PhD, this week on The Rich Roll Podcast. 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, 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 PhD 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. 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 of few, but first. We're brought to you today by recovery.com. I've been in recovery for a long

time. It's not hyperbolic to say that I owe everything good in my life to sobriety. And it all began with treatment and experience that I had that quite literally saved my life. And in the many years since, I've in turn helped many suffering addicts and their loved ones find treatment. And with that, I know all too well just how confusing and how overwhelming and how challenging it can be to find the right place and the right level of care, especially because, unfortunately, not all treatment resources adhere to ethical practices. It's a real problem. A problem I'm now happy and proud to share has been solved by the people at recovery.com

who created an online support portal designed to guide, to support, and empower you to find the ideal level of care tailored to your personal needs. They've partnered with the best global behavioral health providers to cover the full spectrum of behavioral health disorders, including substance use disorders, depression, anxiety,

eating disorders, gambling addictions, and more. Navigating their site is simple. Search by insurance coverage, location, treatment type, you name it. Plus, you can read reviews from former patients to help you decide. Whether you're a busy exec, a parent of a struggling teen, or battling addiction yourself, I feel you. I empathize with you. I really do. And they have treatment options for you. Life in recovery is wonderful, and recovery.com is your partner in starting that journey. When you or a loved one need help, go to recovery.com and take the first step towards recovery.

To find the best treatment option for you or a loved one, again, go to recovery.com. 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. 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, 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 gonna wanna take notes on this one. So without further ado, this is my conversation with Dr. David Sinclair. Good to see you. Thank you for coming out.

Thanks, Rich. Thanks for having me on. 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 wrap my head around what we talked about last time. I was like, wow, we covered a lot in that, right? 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.

Thanks, sounds good. You were over doing Laird's workout this morning, right? I was, it was brutal. So walk me through it. Well. First of all, how'd that come together? It was through mutual friends, it was a bunch of us that have known about this for a while.

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

Yeah. So what that's like is, if listeners don't know, is you start out in a really hot sauna and I'm not just saying a hot sauna. It's like the temperature of the surface of the sun. Yeah. So I normally do 160 degrees at my own gym. This thing was cranked up beyond 250.

It was maxed out. Oh, it was that high? I knew he set it around 200. I didn't realize it was that hot. Wow. 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 go into the deep end. You're underwater below the top of your head by maybe half a foot and then you have to jump up and down. And you think, okay, I can do that. There are two problems. One is if you don't make it,

you're gonna take in a mouthful of water, which is what I did, of course, the first thing. But then the other problem is you go into this panic mode. 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. It is not pleasant. You think-

We can always let go of the weight and surface. There is that, but there's only one thing worse than drowning. But there's Laird standing there. That's right. The judgment of Laird. Yeah, I would rather drown than be embarrassed and give up. So, you know, I looked like a stupid fish, well, 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.

That was my first mistake. But then what did we do? We also warmed up again in the sauna and then we jumped into a big bathtub with ice, with about a couple of inches of ice on the top. And that wasn't so bad. You know, I've talked about cryotherapy before and saunas and hypoxia,

but I've never done it so extreme. I know Wim Hof is the guy to beat, but I usually go to my gym, which is just four degrees Celsius. I don't know what that is in Fahrenheit, but it's not that cold. It's like your fridge temperature. And I found that brutal. But actually going into that ice water, I was fine. I mean, the initial shock right

i can't breathe i'm gonna yeah and then but maybe 15 seconds later uh with gabby uh 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 was great. And I got to three minutes. Actually, I was gonna do two minutes because she thought I was a bit of a wimp. 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. Were you up to your neck? Oh yeah, I actually went under for a couple of times. That was great. And then you get out and you feel great. You feel refreshed, grateful to be alive. And yeah, I would do it again in a second. How many people were there this morning?

There were about 10 of us. Yeah. 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 heard was Darren O'Lean there this morning. He's sort of a layered lookalike. Like, yeah, Darren been on the podcast, very good friend of mine. Sort of a layered lookalike. 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 do anything and kind of attack it from a perspective of 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. Yeah, there's a fair bit of that today. Yeah. Yeah. So Darren and I talked about, he's an interesting guy, right? He's sourcing- Super's super interesting yeah you guys can talk forever we we will we will meet up again good uh and uh yeah the uh justin wren was there oh cool you know

my friend justin wren that was his first time doing it too yeah and he was my buddy mma fighter exactly so justin um what is it fight for the forgotten that's his charity wonderful wonderful guy check him out he was my buddy and first thing I asked him when I was teeing up with him was, do you know CPR? And fortunately, he didn't need to rescue me. Yeah. That's cool. Well, do I have this right? Like, you have some scientific background in thermogenesis, don't you?

Do you know Ray Cronise? Did you work with him on some of the studies that he did on that? Yeah, we published papers together. Right, that's what I thought. Yeah. So Ray and I, interesting story. He was a former NASA scientist, not even thinking about metabolism 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 all people. And he said, David, I've never heard a talk that's convinced me to change my life. I'm gonna do what you do and I'm gonna be a disciple. And I thought, okay, Ray, I'll see you later. But he did it.

And so now what is that? Over 10 years later, he has changed his life. He's a guru for health and particularly cold therapy. And we've published a couple of papers. One is on the metabolic winter hypothesis, the idea that these days we always look for comfort. And one of the problems is we never experience temperature variation in our lives.

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

Yeah. Healthspan, I think it's called. Right, Healthspan cookbook. Yeah. I gave it to my wife for the holidays. You did, cool. Yeah, it's really great. I really liked those guys, both of them.

They make a good combination because Juliana's the cook and Ray's the brain. Yeah, exactly. It is a good mix. They live like right up the street here. Oh, do they? Yeah, they've been on the podcast um cool well i think it's interesting that you you did the laird and gavi 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. 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. Right. And 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. 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 can 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 biggest problems in our lives is that we've just been handled with kid gloves and the food we eat is also not stressed out and that combination just turns us into mush 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. Right. Well, we were working on resveratrol. The resveratrol story is what I first was known for in the science world. And we discovered that 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 xeno hormesis xeno means between species and hormesis is what doesn't kill you makes you stronger and it's uh even though it's a mouthful what what it it explains so much is that when our plants are stressed that we eat uh 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 hill or you're eating fruit that's just had a massive drought, you're going to 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. That's like different species communicating with each other through some, you know, unheard language. 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. 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.

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? That's exactly right. That's what I think we should be doing. And there's a business idea. Okay. And in fact, Laird was telling me just an hour ago that I didn't know this, that people who grow oranges and know what they're doing, drive a nail into the tree,

I think it was a day or so before they pick the fruit, and that gives it these extra flowers. Oh, wow. That's interesting. Yeah. So 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. 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 xenochormatic molecules as well. So how does that, I mean, 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 it about organic that relates to this? Well, there's organic and there's real organic.

I'm talking about the plants that may have had a grub, eat it or are exposed to too much sunlight, that kind of thing, being out in rougher conditions. Yeah, hyper organic. Right, right, right, not pseudo organic. That's the name of the new company all right let's do it yeah um that's cool well when you look at laird i mean he's sort of a uh an experiment in motion right like what is he 55 now yeah i think um 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 somebody who's practicing a lot of the things that you talk about. I mean, I don't know what his supplement routine is with respect to some of the research that you're doing, but in terms of his daily exercise regimen and lifestyle habits, it seems to be, to comport with the things that you talk about often.

Yeah, right. He's the orange tree with the name in it every day. Right. But I totally believe it. But you don't just do it with hot and cold and you don't just do it with 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 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, that eating less food was healthy because it lowered inflammation somehow. What we've realized is that all of these things are working through the same mechanisms.

And it goes back to work that we did in my lab 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. It turns on defenses. We found that these yeast cells lived 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're 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 even today, most people don't realize that all of these things that we do

are converging on this master regulatory pathway for our health. Is that part and parcel of this kind of singular information theory of aging that is sort of the foundation of your work? 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 send out the troops to repair and fix things. And one of the main 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 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. 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 on the book, right? The Demented Pianist, where you explain all of this. The metaphor that we used was highway traffic, right? And getting dispatched away from their true role to kind of deal with crises, potholes in the roadway and whatnot. And then the signaling getting screwed up. And then basically all of the kind of traffic copying going haywire.

And the NAD isn't going where it's supposed to be going, and the sirtuins aren't where they're supposed to be, and the whole kind of system breaks down. That's right. And we first discovered this, I was at MIT as a postdoc originally, moved to Harvard in 1999. Those years 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. Now, what we also realized was that you can distract them from their main job. The pianist can get distracted. Imagine you start trying to whistle or get in the face of your pianist. It's essentially the same. And what 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. 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, this 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 make it back to where they should. And over time, that's cumulative and you end up with a cacophony. So the goal, the job, the mission

is to maximize the efficiency, to really optimize the sirtuin functionality. Right, and the way to do that is to make the body think that 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 sort of things. Because then they're not distracted by these sort of frivolous situations and they're focused on the most important job that they're kind of created to deal with.

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 get detached from what they should be doing and then they drift off through the liquid in the cell and they don't have enough energy 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 resveratrol is also an activator. That's one of the things we figured out in the 2000s. So the combination of the fuel and the activator, resator is virtual and the NAD is a fantastic combination we think for maintaining that epigenetic symphony as we call it. Right. So what is the state of the union when it comes to the scientific research on sauna therapy, cold therapy and its impact on NAD and sirtuins and thus aging or anti-aging? That's a really good question.

You just got a big smile on your face. Yeah, I can see why you're so good at what you do. I'm just trying to follow my curiosity here. I'm trying to keep up and I really want to understand this. So anyway, go ahead. and I really wanna like understand this. So anyway, go ahead. Well, so the connection is that the sirtuins are actually 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 these sirtuins 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 so glad. Yeah, we definitely didn't talk about this last time. Right, so I haven't talked about it publicly.

NAMPT is the master regulator of NAD production. It's the, 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, we what we call heat shock them

and on came this NMPT 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 degrees Celsius, that is making my body make more NAD, essentially mimicking the effects of exercise and hunger, just a different way, and making my sirtuins work optimally and that is something that i think is underappreciated that this one gene is the probably the main cause of the benefits of all of the things that we have figured out over the last 2 000 years of being healthy 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? Not well. Yeah. No, no, and I'm asked all the time, what's the best combo of diet, exercise?

We're figuring this out. And then, you know, the keys of the kingdom arrive. 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 hormesis-inducing protocol that's going to activate this NAD producing signaling mechanism. 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. Right. Cause you, you acclimate to that, right? And it's no longer, it's no longer creating the stress response. Exactly. So I don't exercise every day. Not that I could, but I don't.

It's a convenient excuse. Yeah. Really true. You got to 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? Right. You got to, you know, switch it up. And that's why I think that the best thing that we know right now is that you wanna do some exercise, then you wanna do the sauna, then you do the ice bath.

That's what I do. And until I know more, I'm gonna keep doing that. Right. Similarly, I would imagine, when you look at Walter Longo and his fasting mimicking diet and all the science that's emerging around intermittent fasting, I mean, the benefits of that are kind of boiled down to hormesis, right? You're trying to create a stress response that activates certain pathways in your system that relate to

aging or anti-aging. But I would imagine that 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. Does it work that same way with the eating? Well, it's complicated because there are two experiments that have been done. 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 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. You never get used to not eating. Yeah. Yeah. Your body will still respond. But at least we understand what's going on. And again, it's this NAMPT gene in large part that's turned on when your body doesn't have enough glucose and insulin is being produced. But also this intermittent fasting, the reason I like it, and 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. The intermittent fasting for me is better because it means you can eat instead of 70% normal calories, you can eat 95% or 100% calories. You just have to squeeze it into a window of a few hours to be optimal. And that's just easier to do. 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, they both work about the same that, you know,

you can argue about minutiae, but basically they all extend lifespan. But the mice that are on intermittent fasting can eat a lot more in their lifetime. Yeah. And, you know, if you're not eating food and enjoying life, you know, it's not worth it probably. But I need to get hormesis, hormesis.

I'm gonna starve myself. Well, yeah, I'm skipping one to two meals a day and it's changed my life. I feel great. And a lot of people say it makes me feel queasy or my stomach's burning. I found I get used to it. And if you find that it's too hard,

try a cup of hot water. I think coffee is great, tea. And that gets me through the morning. Yeah, I've been playing around with it and experimenting with it for a while. And I found that so much of this is psychological and mental. Like I'm now in a place where 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 not even really thinking about it and where you really realize, realize it. And I know you posted about this on Instagram the other day, uh, is when you fly, when you, when you get on a long plane. And I use those generally as opportunities to, to play around with this thing. Cause 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 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 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. Right, they're saying, 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. I know, the more you say no, the more they come back.

That's been my experience, I know, yeah. Yeah, but I agree with you. It's a moment to really test yourself because you're sitting there and all you've got to think about is the food and the person next to you is eating. Right. And 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, it's fine to eat now, but what do I wanna look like, feel like a day, a week from now, 30 years from now? And that allows me to help my future self. 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? No, I'm still 50, but yeah, no gray hair. I'll let you know. No, yeah, definitely not a gray hair on your head yet. And 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. Yeah. Can we talk about that? Yeah, that's really important. It's a massive breakthrough in the field of aging for many, many reasons. One that? 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 non-subjective measure. And we finally have that, finally. Until recently, all we had was some blood tests that tell you 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, one of my very good friends, great guy,

he's a mathematician by training. And somebody gotvath, Steve Horvath's one of my very good friends, great guy. He's a mathematician by training and somebody got their clock measured by him. 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, 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 but he's got a great dry sense of humor uh 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 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. The clock is measuring the pianist's state of mind, right? 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. But when you're born, you have a certain pattern of these, what are called methyls. These are little chemicals, just carbon and three hydrogens that bond to the C letter. You know, on DNA, there's A, C, T, G. So the Cs get this methylation, it's called. It's 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. And then once you've got that straight line, he or 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.

Oh, wow. I would imagine that gets more and more accurate every day, right? As the data set grows. 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 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. So we want to figure that out, how that works. 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 a way to actually quantify that. So what is your age according to the Horvath method? I don't know yet. And when are you gonna die? What do you mean? You don't know? No, no, I've been too busy.

But no, I've done just the old-fashioned blood tests, 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. I think a really good deep test would cost at least 300, sometimes a thousand 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. Right. If you're brave enough. There's another business for you. Yeah, well, 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. Right. 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 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. Wow. Yeah. Then the data becomes unbelievably valuable, right? 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. 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 kind of scared

to look. Yeah. What would happen if it said, you know, here you are, the anti-aging longevity guy, you're going to die in two years. Yeah, that would be a bad day. That would not be good for business. Yeah, well, you know, 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 I might actually be older than I look. Who knows? I will tell everybody when I get that data. But here's the really important point, Rich, which is that data is important.

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? Do you just go to bed and have depression? 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. Right. Since we last spoke, has there been any interesting breakthroughs or new studies or science that has kind of shifted or expanded your perspective on any of the things we talked about last time? Yeah, lots. Every day, 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 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 bodies make. We call it the endogenous activator, the elusive endogenous activator. And what this paper showed was that the byproducts of what we call lipolysis, the breakdown of fat when you're hungry, produces monounsaturated fatty acids, the kind that you can get from olive oil. Right. Those molecules circulating in the blood

are about a thousand 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 uh we've kind of been vindicated because we got a lot of crap for resveratrol yeah in the early years if you if you google your name and resveratrol there's a there's a lot of shit talking coming in your direction uh yeah earlier stuff from years ago well yeah and it's

been it's been a brutal uh 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 pharma companies, and their scientists said, literally, that is bull. Right. 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'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 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, you know what? I'm gonna test this. And he worked really hard and figured out that the experiment that we originally did to show that resveratrol was activating the enzyme

in the test tube was not an artifact and that it was actually real. So we published that in the journal Science in 2013. And so the scientific hubbub went down. Basically, we were largely accepted that we were correct. But out in the media, no one cares about correction of a scientific idea. Yeah, of course not. It's all about the controversy that's interesting.

And so that's still out there in the world. So anyone listening who knows that this was controversial, we've actually scientifically resolved the controversy of 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? 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 situation so that we are creating this impact that we're trying to have. I mean, what do we do with this information? Yeah. Well, I think 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 nanomolar for the aficionados activator of SIRT1.

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. Or alternatively, in lieu of olive oil, you can get the same result via resveratrol. 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. Right. That's a good thing. We talked a little bit about this last time, but I think it's worth exploring a little bit more. What is the difference between taking in resveratrol via red wine versus a supplement in terms of bioavailability and your body's ability to kind of metabolize it. 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 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. So for worms, we use a thing called DMSO.

In humans, we found in the early 2000s that if you mix it with a fatty meal, and that's true for mice as well, you get about five to tenfold 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 with a meal or something that the resveratrol would dissolve in.

Right, so there is some sense that that definitely increases the bioavailability and absorption. 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 humans. That's also not very well known. And there's 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 actually is I don't wanna complain because I've been very lucky in my life.

It saddens me that in science, you can be derailed by a decade, for a decade by your naysayers. And I'm hoping to get things back on the rail, seems like so far so good. Well, the last time we spoke, this book had not come out yet. Now it's been out.

You've been doing the, you did the book tour thing. And 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 aging is reversible, that we're on the precipice of new science and breakthroughs that are gonna revolutionize how humans live their lives and think about their lives. And on the other hand, you know,

some pushback from the conventional scientific community and some grumbling amongst, you know, the old guard saying not so fast. Exactly. You know what I mean saying not so fast. Exactly. You know what I mean? They hate fast. Yeah, you've got your foot on the accelerator and they seem to be saying,

slow down, you're kind of out over your skis here. Yeah, that's true. But that's, 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.

I 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, uh-uh, don't be so sure of yourself. But yeah, it's tough as a scientist, especially one at a conservative university like Harvard. I often get my knuckles wrapped because I'm out there. Right. But I do it not because I'm out there. Right. 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.

do think that it would be a real shame if our generation was the last to live a normal lifespan. 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? I mean, what is the purpose of a lab if not to test the limits of our understanding and to kind of dream boldly? and to kind of, you know, dream boldly. 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- That never happens.

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 scientist says we're all gonna live to 150. Right. Which I'd never have said, but then the university says, David, what the heck are you saying? 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.

Right. And I appreciate it. Not getting misquoted. Yeah. And how's the lab doing? And how are the colleagues? Like in the wake of the book's success, New York Times bestseller,

like it's books everywhere, everywhere you look, I see it. How are they kind of acting towards you now? Good. I've had no backlash about the book, which surprised me because it's a bold thing to say that we figured this out. It upsets a lot of people, right?

But as far as I know, they're not upset. In fact, I've had a lot of praise from colleagues. It's cool. I mean, congratulations. I really think that it is a paradigm-breaking masterwork. And what's really interesting and unique about it, and I suspect sort of unexpected for somebody who's going to pick this up, 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 I was expecting looking into it. Like it's

kind of genre bending in that regard. Well, thanks. I appreciate it. You know, anyone who knows me, I'm not really a scientist. I'm doing science because I have a goal in life. In high school, I was an artist and some of the illustrations at the back of the book,

I drew myself the headshots. So I'm an artist masquerading as a scientist, but I think they go well together, actually. I think in terms of shapes and things moving around, I'm not so much a mathematician. But 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,

especially also when you look at society. And a lot of things are said about the work that we're doing. Oh, we're all going to run out of jobs. We're going to have not enough food. What are we going to do with all these people of a population? If you look back at history, we've always been worried about that. Right. 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 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. 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? Yeah. I think we probably overlapped. Yeah. And, and it was quite something being in Sydney amidst these fires.

And 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 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. 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 craziness. 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 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 really brings home the fact that we are living 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 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. It's not that hard to admit unless you've got some other agenda. And Australia is a,

if you've never been to the Australian bush, you 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 oil mainly and it's not hard to start a fire a bit of you know throw a cigarette out or whatever once it's going this is basically uh 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 because the truck was caught in a tornado and blown on top of them. That's Armageddon kind of stuff. And you go there and there's just this, I think the Australians are in shock. 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 I see now is that, this is not a one-off. Fires in Australia normally start in around February

and we're in December or January and this could be the new normal in California right now, it's fires all year round pretty much. Yeah, and this fire in Australia has been going on for like four months at this point, right? Right, right. I say fire singular, but it's a lot of different fires that are meeting up with each other, et cetera.

Yeah, yeah, it's a scary world and we have to do something. And so most people look at me and like, oh, David, you study mice. What would you know about climate change? 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 got to take money from somewhere to solve these problems if they 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? Right now we waste billions of dollars taking care of the elderly who don't need to be old. 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 80s are just starting a new career like my dad did. That's a world where a globe that would save trillions of dollars. Okay, so now it's easy to say you save a 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 1840, the cholera thing that I then mentioned, people in the 1840s, 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. 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 a sense of just how conservative the government is and everything that's going on with the PM and he goes to Hawaii in the middle of all this on vacation and the impact of the coal industry on kind of 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 excited about the potential of our species 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 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.

Yeah, no doubt. No doubt. And just to hit the exclamation point, old London, when they figured out that it was actually cholera from the water well, 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. 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. 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, 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 fda has actually agreed that if we do certain 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's right that we can prescribe medicines for. 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. No, no. Nobody has any reason to say that we have this clock that cannot be changed. In fact, what we've learned going back to the Horvath clock is that about 80% of our lifestyle, 80% of our health in old age is due to our lifestyle and how we live. And only 20% is genetic. And actually that's done by studying twins who, you know, some smoke, some don't, some do all this stuff. 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. 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. But fortunately, 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 80, he's still running around like he's 25. 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. What was it? Something like 180 pounds, something a lot. And he said, the last 80-year-old that I trained was learning how to get out of a chair. Right. Yeah, you posted something on Instagram. He's like, you know, in the squat machine or whatever,

like just killing it at 80. The guy's in his second career. He's had this kind of, 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 80, like crushing it,

it's very inspiring. Well, I think most of us can achieve that in life. Now there will be unlucky people, of course diseases still hit us, but most of us are wasting our lives because we're basically, not you, but most people don't think about their longevity. 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. 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 healthspan, 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 the, you know, dominant paradigm in order to kind of thrive later in life. Yeah. Well, the dominant paradigm 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, they only see patients after they get sick. And so the aging process is already pretty advanced at that point. And aging is, let's not 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, these diseases are real, but they're the end point of this process that we're working on. But most doctors don't think about aging. They don't think about what got people to 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 do need medicines. We need to treat diseases, but it's a little too late for a lot of people.

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 paradigm of coming 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. Let's talk a little bit about the ethics of your work. So we were talking about Australia.

If we just look at what's happening there as a symbol of climate change in action and a kind of degraded planet Earth and a certain trajectory that we're on and have been on for some time. Somebody who, by your own words, said, 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 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 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. 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 not the doomsday that we thought it was in the 1970s. Malthus and the Ehrlichs used to panic,

make all of us panic because they said- About global population growth. Well, about you're running out of resources. If you extrapolate this curve vertically, of course, we're all gonna 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. And then you have women who become educated and women don't wanna have 15 kids.

They don't wanna 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, 15 kids or 13 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 I'm drawing these curves. Anyone who's listening can't see this, but basically we're tapering off this exponential growth. We're going to max out, according to the United Nations World Health Organization organization at about 11 billion now that that's still a lot of people of course max out on on the resources 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 why wouldn't we just continue to populate until we blow through that ceiling? Well, because 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. Yeah, I mean, this is one of Paul Hawkins' big things when he, in his book, draw down one of the most powerful tools in the war against climate change

or the battle to solve this problem is educating girls. The more we can educate girls in the developing world, they're less likely to have as many kids, right? Exactly, exactly. So we're gonna 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 need our help. But you're right, being a woman in these countries is the worst. If they don't have a well, they have to walk. You know, thanks to Justin Wren, he'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. Right. Conversely, as a thought experiment, let's say you could live 200 years and and a you know 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 right? Like you could have kids and they grow up and you get older and then you get a new career and then you could just say, hey, let's do this again. Yeah. Right? 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. Right. Anyway, I'm proud of him. He won't mind me mentioning his name, Norman Lear. He's fantastic. Okay. Norm's one of those guys, but most people don't do that.

Yeah. But it's possible. 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 remain vital later in life, like the idea of having a child at age 70,

if you're operating the way you were when you were 40, seems like not such a bad idea. Thank you for saying that. Because this isn't about science fiction, living to 170 and having 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? Or do you want them to spend another 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 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 there'll still be people who don't take care of themselves and i'll be sick at 60 that'll always happen but on, people will continue to live longer. We've been on this trajectory of living healthier

and being more youthful in 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. Yeah, when I was 10 years old, if there was a 55-year-old Laird Hamilton doing what he was doing, 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. 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 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 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 right

um 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. I mean, 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 gonna live to 300, barring me getting hit by a bus, like I have a lot of life to live.

So am I really gonna go skydiving? Because then the risk of that seems so much more severe than it would if you're looking at, well, I'm gonna only live to, you know, life's short and I'm gonna die at 80 anyway. Like I'm gonna 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?

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.

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 won't want them to go outside without a helmet on. Oh, it's extreme. Walk down the street. 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. Oh, really? The red, yeah. And it's got- How does it shame you? Like a photo of your face?

Yeah, right on the street. You can see the lady that crossed the street this morning that disobeyed the rules. And she apparently has demerit points on her social score. Oh, that's just like, that's black mirror stuff right there. Yeah, scary stuff.

Hopefully this world that we live in won't be like that anytime soon. But yeah, the risks will, you don't wanna take massive risks. But you know what? I think that 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 there are risk takers and most of us will still take risks in life. Actually, 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. Oh, you are? On the road? I'm not, well, not anymore. I'm now a bit sedated, but I shouldn't say sedated, but I'm more calm about my driving.

But I do drive a fast car. I drive a Tesla and floor that. But I do like the feeling of risk. And it's the reason that I'm in this career in the first place, because I took a lot of risks when I was young to get here. Point being, you know, maybe I'll live to 100, maybe I'll live to 150, I don't know, maybe I'll die tomorrow. I don't care.

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 the world is that the longer we live, the more scared we become of danger. Right. Fireworks, are we gonna worry about fireworks?

Yeah, that kind of thing. 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 1840 London. Yeah. from today as we are from 1840 London. Yeah, I think in tandem with trying to elongate lifespan and healthspan,

we also have to solve these other kind of 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 in alignment with what's required to be fulfilled and to be happy and to have purpose for living that long? Yeah, 100%.

So there's the world of molecules and genes 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. Because that's also what drives me. And so I think you're right that if you're someone who's prone to depression, giving up hope, you got to get out of that. You got to find what excites you, what drives you. I teach a lot of students at Harvard, and there are some students who are very smart, some of the best, brightest in the world, but they're, I'm not sure I can do that, whining around.

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 it's finding something that you want to go for and change the world. And 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. Yeah. It is interesting that it dates all the way back. Your whole life has been infused with this drive you know, this drive, this passion to, you know, solve this problem or, you know, basically advance humanity in this way. 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 anyone 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 not riding high. I still have massive ups and downs and obstacles even at my age. But I've learned actually that if you have a goal, that's what gets you through it. So when it's all said and done, like what is the legacy that you're working to leave behind? Like when you're complete, what does it look like ideally?

Well, of course that's never gonna happen. But you hold this great vision. So what is that vision? Well, I would love 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, we're talking about career arcs. I mean, what about a world where if, you know, not everyone can have their dream job initially. I would love a world where people can live to 150, expect to be still playing tennis 120.

I think it's doable. There's no reason why we can't do that with our ingenuity. But 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 gives you, you know, let's go back in time a little bit, 1840. Okay, that person who's born in 1840 was not expecting to have, first of all, a great time at age 40 or 50. Basically, 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'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 radical, which is, well, it's another chance. If you're busting rocks or whatever that you hate, two years off, retrain, get another chance. two years off, retrain, get another chance. And if you have a long life that's 150 years long, you can do, you know, one career could last 20, 30 years, become the best you can be at that and then switch.

And that's a life that would be well lived, wouldn't it? Yeah, I think it would give people the patience that I think we lack right now. Like we're in such a hurry from the moment we're born. It's a habit trail of achievement and measuring ourselves against others. And from the moment you enter junior high school and then it's grades in high school and it's getting into college, it's this race, right? grades in high school and it's getting into college. 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 know? I mean, you knew what you wanted to do at a very young age. Most people don't, right? But they're kind of corralled into a certain path and on a trajectory that for

a lot of people, 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. Take your time. Go on a kibbutz. Maybe there's a national sort of period of time where you, 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. Yeah, I couldn't have said it better. 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, he's still perfectly fit. What am I going to do with my life? He started a new career. And so instead of being 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, if 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. 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 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. And hopefully a greater appreciation for the wisdom of the elderly rather

than just warehousing them in nursing homes and and trying to put them out of our line of sight and and you know dismiss them which is the tragic situation that we're in now yeah it is that the older you get actually the more you appreciate the these folks uh 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. Right.

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?

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 modern times, who's stuck in an era that is bygone sort of plasticity 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 of this whole thing. It's not perfect, right? There'll still be people who are in positions when they're too old to deal with the current. But now it's like, finally, that, you know still be people who are in positions when they're too old to deal with the current. But now it's like, finally, that these people are, we're getting rid of all these people so we can get fresh blood in here and a new perspective.

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 a 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 Bill Gates, same. There are people you wanna keep around. Maybe there are a 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. 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. Yeah. Yeah. You're going to be cagey about this, right? Well, yeah, yeah. I mean, it's, you know, look, we all want to 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.

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

I don't name drop, but I've met a lot of my idols in business, in Hollywood, a lot of billionaires. I probably met a quarter of the world's billionaires at this point. Yes, that's good. But I'm learning a lot. You're the Ponce de Leon, right?

Yeah, well, I am a spokesperson for this field, but I should say that there are hundreds of scientists like me working away every day to help solve this problem. 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 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 a medical doctor and I'm not going to give you a prescription for your life and I'm not going to give you advice about 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? This is what people are like, well, what do you do? Like, you're the one who knows more about this than almost anybody. So tell me what your habits are. Right. Well, 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. Right. Okay, there it is. 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.

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 part of this monastic group of people that should only say something if it's factual, right? And I try my best to do that. The supplements that I admit that I take,

and that's rare for a scientist to admit that stuff, even though probably about half my colleagues are do that. The supplements that I admit that I take, and that's rare for a scientist to admit that stuff, even though probably about half my colleagues are doing something. I'm out on a limb. Now, anyone who wants to jump to the page that Rich talked about, it's page 304. It's page 304. Yeah, I get asked that a lot.

Oh, do you? Yeah. That's so funny. But I've realized that there's 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 adding to those pages. Now, it's not just one page to be fair. The whole of part two is about what you can do in terms of fasting and exercise and why it works. Where you just kind of break it down and here are the things. Well, that's a cheat sheet towards the end. But yeah, 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 gotta be objective. Also, I don't spend my time testing products. That's not what I do. I'm a molecular biologist geneticist. But 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, 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 or supplements, there's a lot of other scientific work that they can delve into as well. Yeah, the notes, I mean, the notes go on for,

how many pages, 360. Yeah. So like 50 pages of notes at the end. 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 not written by scientists, you can bet that what you're reading is factual as far as we know. Well, let's talk about what it is that you do. In your estimation, what are the most important things that, and again, you can preface this with whatever caveats you want,

but what do you think are the most important things that people should be doing or looking after on a daily basis to kind of take out an insurance policy against aging, given the current state of knowledge and understanding. That's well put. Okay, now I feel free to speak because I don't endorse and I don't recommend. 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 literally think 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 gonna go out on a limb to say that a lot of nutritionists would disagree with me, but I've been doing this for 30 years. I've seen what happens to people and animals when you restrict their food. And 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 for as long as you can do it.

I do it, like I said, hopefully till late afternoon dinner. That's the easiest and best thing 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. Right. You're going back tomorrow, right? Yeah. Well, I will do it again, actually. Now I actually think I know not to go too far into the deep end. But honestly, we now know we all have the power with the scientific basis to actually live at least 15 years longer. Okay, so there are actually, and I talked about this, I think, on Twitter recently, that there are five things that are pretty obvious and easy to do

that'll give you 15 years. And that's just off the top of my head. Things like exercise, the fasting, don't eat too much, eat the right foods, try to be plant-based, get sleep, have social network. That gives you 15 years. That's amazing. That's not even delving deep into my book,

which takes it to another level of what the best exercise and supplements probably are. So that's the good news. I do list a lot of things. We could talk for hours about what I do. Page 304, you'll see more. I'm conscious that we have a microbiome that needs to be healthy. So I make my own special yogurt,

which I mix my resveratrol in. I think I'll release the recipe of that pretty soon in the newsletter if anyone would like to make it. So these are the things. Sorry to interject, but you sort of said, eating plant-based, predominantly plant-based. I mean, a lot of that is informed by the relationship between excessive protein intake and that impact on aging, correct? Well, it's both.

From your perspective in the work that you're doing. Right, right. Fair enough. So there are at least a couple of things to talk about. One is, so Dan Buten is right. And I've 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. It makes a lot of sense. They're activating longevity genes. So the plant-based food,

I think a little bit of meat is fine, especially if you work out and you're trying to 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 humans. And they are mostly plant-based with a little bit of meat like fish. So why does that work? Okay. Why do we think that works? The two reasons, one is that you don't want to overload on certain types of amino acids, which you'll find in meat, leucine, isoleucine, valine. These 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 big deal mTOR. But if you're always eating 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 most people miss, which is the xenohormetic molecules from plants. You get those. You don't get those from meat as much. So what do you make of the carnivore diet? Yeah, I'm on the other side. It is an interesting phenomenon. It's good long-term. 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. This story very much has yet to be fully told. But if somebody's listening to this and perhaps is flirting with the idea of that, I mean, what would be your response to that person? 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. 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.

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. There's a need. 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.

But you could- We're on our own. So we're gonna have to do the heavy lifting here. It's basically catalyzing these systems, these biological systems to protect the body, right? Yeah. And in turn promote longevity versus, oh, we've got an endless supply of food coming in here.

We can just shut everything down because we don't have to worry about it. 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 defend against issues. By eating a lot of meat, I think what you're likely to be doing

is accelerating that process towards older age. Because 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. So you've got to get your defenses up like you're a baby. Speaking of which, I've been on a much healthier diet the last few years, including intermittent fasting,

including the supplements that I've got written on page 304. One of the people say, oh, I'm not noticing anything after maybe two weeks on supplement. Of course, you're not gonna 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 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. So my immune system must be on hyper alert. And why is that good? 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. My father's like that. He doesn't get colds even. What about sleep?

Have you looked at the impact of sleep on all of this? Some people have. Well, we've done a little bit in mice. What we've discovered is that the sirtuins 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. And if you're screwing up your longevity defenses, you're also probably screwing up your body's clock. And if you're screwing up your longevity defenses, you're also probably screwing up your body's clock. So another side effect that I get with this new lifestyle is I get much better sleep. And I know that. We've got rings that can tell us that now. And I feel great.

I don't wake up tired anymore. 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 if you get that out of whack, we get this thing we call jet lag. 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.

That's interesting. Wow. That's super interesting. All right, so fasting, trying to create some hormesis in your life, basically living a blue zones lifestyle. In terms of supplementation, I know you're not gonna give 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? Correct. A different version of that would be NR, right? Which is like one step removed from that same process? 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, no, that first step is this NAMPT gene. Okay, so yeah, people are taking NR or they're taking NMN. NR is a little cheaper than NMN. 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 I find that it produces some better effects

in mice when say for endurance. But the truth is, even though there's a lot of chatter on the internet and some of my colleagues have their stakes in some companies, by the way, I don't benefit from any supplements ever. So I have no stake in this. But some of my colleagues 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 they're the same. I take NMN because A, I have a ready supply because we're doing clinical trials, but also because I've studied it the most.

And that's it, right? There's no other, is there anything else that you're taking? Yeah, yeah, there's a bit of a list. I'm also taking a drug. Ooh, a drug, right? A drug called metformin, which is the diabetes drug. 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, 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. Other parts of the world, 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.

So what prompted you to get on metformin? Oh yeah, really simple. My best friend told me to take it. No, but in all seriousness, so his name's Nir Barzilai. He's considered the world's expert in this. But 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 100,000 people, in some cases they're veterans, but mostly older people 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 metformin have a much higher risk of Alzheimer's than those that took metformin. And the same is true for some cancers and frailty and heart disease. So what is that interplay? Like, why would that be the case? Right. Well, there's a lot of debate about how metformin works. The main explanation is that interplay? Like why would that be the case? Right, well, there's a lot of debate about how metformin works. The main explanation is that there's an enzyme called AMPK or AMP kinase that talks to the sirtuins.

So they're actually interplay 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'll tweak the other. But I think what the best is to tweak them both just at moderate levels and get 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 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, you can't have too many mitochondria. That's the key to being a good endurance athlete, mitochondrial density. It is. It really is. And actually, as we get older,

we lose about half of our mitochondria. But one way to boost that is to take metformin or to do these other things like exercise. But it's not all good news. There are some studies that show that metformin can interfere with endurance and muscle hypertrophy. And there's been a lot of talk about it, actually, on the internet. Peter Atiyah has done some work, podcasts on this. Nir Barzilai, my good friend at Albert Einstein College of Medicine, was on that study. So 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, and I'm going to be using my hands for graphs, but basically 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 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, pretty simple solution. But I still think on days where I'm not working out, metformin is gonna protect me against these major diseases. So your impetus to get on metformin didn't have to do with elevated blood glucose

or insulin resistance. It was more from this sort of longevity, self-experiment perspective? Well, it's both. There's never one answer to these things. My father and his father and myself, we're susceptible to obesity and diabetes. 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. 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 also a factor, no question that I took that into account. I didn't take metformin

before I got diabetes until recently, 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. The worst that I get is an upset stomach and actually 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, I forget which type of cancer, but it's in the book, can be lowered by 40%. That's a massive, massive effect. So you always got to balance it. So I don't prescribe anything to people.

But what I would recommend to do is to think, what risk am I willing to take? What are the potential downsides? And with a drug that's been in millions of people, there's a risk, but the risk is pretty low. How old am I? You know, if I'm 110, I've probably only got two more years. So what's there to lose? So that's obviously a calculation. And then how expensive is it, right? Some of these things are still just very new to the market. And all of that has led to me adapting my life over the years. Admittedly, some of these discoveries are fairly new, so I haven't been doing them longer than I would have

preferred to have done them earlier. But that's the calculation. And so 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 we think feels comfortable, the end is not pretty. I've seen what happens. The other thing that I wanna talk about or just mention at least is smoking. So my mother died of lung cancer. It was brutal to see her pass away.

She had a lung removed, right? She did. And then her final lung gave out 20 years later. So she lived for 20 years on one lung? She did. And then her final lung gave out 20 years later. So she lived for 20 years on one lung? She did. Wow. She managed to live a pretty good life. She visited about 18 countries after that. But the way that she passed away, I don't know, have you ever seen someone die?

Not in that way. Yeah. I've never seen someone die except for my mother, 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. Yeah. If you could, 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 what would that look like and what would you hope to establish well we i don't have to imagine that we're doing design one well so i mentioned near again near barzilai 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 tame or tame what is? 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. And if we're right, we'll be able to show with those numbers of people that A, their clock has slowed down, but B, that they remain healthier

because of, in this case, metformin. But 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. And what's going on in your lab right now? Like when you go back home, what are you working on?

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. 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 anywhere in the world can look at it. If you'd like, you can go to a place called BioRxiv, B-I-O-R-X-I-V. Okay? If you type in reprogramming in my name, Sinclair,

you'll probably find it too. We'll link it up in the show notes. Great. So we're very proud of that paper, which is still under review. So it hasn't hit the media. Actually, I got to say, I know I'm rambling here, but podcasts are a fantastic way of getting news out before the actual news, before I figure 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 say what it is. And the abstract of that study is what? Yeah, please. Yeah, so the summary is that those methyl groups that are counting that we use to count the clock, we can tell the cell to remove the right ones so that the cell remembers how to play its genome correctly like it was young.

There are three genes that we take from out of the book of embryo. So when you're an embryo, you're using three particular genes to grow and be healthy. They get switched off by the time we're young adults, even while we're babies. If you put them back in just at the right time, the right place, at the right moment, we found that we don't see any safety issues. So that's the good thing. What we see is the clock gets wound backwards. Those methyl groups go back. Long story short, the cells are reprogrammed to be young again, completely.

Not just a little bit, not 2%, not two years. But we can take it, for example, in this paper, you'll see, 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? I mean, that's gotta be about as exciting as it gets, right? I mean, that's pretty remarkable. I've seen a lot. This is pretty amazing. Wow. And our colleagues, and I have to credit, we have a lot of help.

I don't know my way around a mouse's eye 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. Excuse the pun.

We've got restoration of vision. I want to run down tomorrow and tell the FDA this is possible. Because 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'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? And where is the reset switch? What's the repository of the information? Put another way, where's the backup hard drive

of the cell? Right. So when that analog system gets scratched, there's an ability to reboot it with a digital replicant that is perfect. 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 DNAna 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 and obviously you know human beings are infinitely more complex than mice uh but what can you extrapolate from that to give you confidence about applicability and in a human context?

Right. Well, we don't know, but 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 penis 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 um in the dish uh 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 possible. But 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. 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 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 eye, it's not gonna grow back like your skin. So we thought, let's go for it. My student, Wan Chang Liu 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. Now you're just getting crazy, right? Well, you got to 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 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. 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. Well, more will be revealed. We will come back. I'll come back and tell you how things are going. Yeah, please do. We will come back. I'll come back and tell you how things are going. Yeah, please do.

We're all counting on you. You have the civilization rests on your shoulders, the future of all of us. Well, and in the meantime- In the seat of your lab. 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.

That's encouraging. That's gonna 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 learning it for all of us. So come back and keep us up to date on everything that's going on. I'd love to. 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. Yeah. Right? Wherever good books are sold.

And David is easy to find on the internet. It's just at David Sinclair PhD on Twitter, on Instagram. Yeah, wherever good books are sold. And David is easy to find on the internet. It's just at David Sinclair PhD on Twitter, on Instagram. Yeah, Twitter is David A. Sinclair. Cool. Awesome, man. Anything else you want to let people know about before we ended here? Let's all celebrate 80 years from now. That sounds good, man.

It's a plan. Where's the party going to be? Your house? I think we'll do it at your house. All right, good. Thank you, man. It's a plan. Where's the party gonna be? Your house? I think we'll do it at your house. All right, good. Thank you, man. Talk to you soon. Peace.

Bless. 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 at David A. Sinclair or on Instagram at David Sinclair, PhD. 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 going to 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 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 forward slash donate. 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 forward slash 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 Margo Lubin for video. Jessica Miranda for graphics. Allie Rogers for portraits. Georgia Whaley for copywriting. DK for advertiser relationships, and theme music, as always, by Annalama. Appreciate the love, you guys. See you back here next week with another PhD,

Cyrus Kambada, along with Robby Barbaro 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 you guys are going to really enjoy it. I think it's going to really surprise you. And here's a clip to take you out. Until then, peace, plants, namaste. I think part of the problem here is that doctors are not trained in nutrition, first of all.

So they go through medical school. 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, I don't know. I learned one class one day, maybe six hours. And there are studies that actually show that your 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 tool set.

So they leave medical school, they go into their practice. And then when they, when somebody with diabetes or high cholesterol or hypertension presents to them, their solution is like, well, I have this pill that I can prescribe for you because that's the system that I know how to do. 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 bug glucose meter. You're constantly getting feedback all day long. Right. And like you said, we're going to get into the weeds on 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. It's massive. Absolutely mind-boggling. Thank you.