Good Life Project - How to Live Longer (and Better) | David A. Sinclair, Ph.D.

Episode Date: November 10, 2022

Question for you: what if you could slow down, stop or even reverse your aging process? What if you could live, not just longer, but better? Extending and even potentially expanding your physical and mental health and well-being. Staving off decline or illness. Is any of that really possible, and what does cutting-edge science have to say?That is what we are talking about with today's guest. David Sinclair. David is a worldwide leader in aging research. He is a Professor in the Department of Genetics and co-Director of the Paul F. Glenn Center for Biology of Aging Research at Harvard Medical School.He's best known for his work on genes and small molecules that delay aging, including the sirtuin genes and resveratrol and its precursors, which we get into. He’s published over 170 scientific studies, is the co-inventor on over 50 patents, has co-founded 14 biotechnology companies in the area of aging vaccines, diabetes, fertility Cancer Biodefense. His book Lifespan, Why We Age, and Why We Don't Have To explores what we get wrong about aging and how to approach it differently. And, his podcast, Lifespan, explores healthy aging and how to live not just longer, but better, too. So excited to share this Best Of conversation with you.You can find David at: Website | InstagramIf you LOVED this episode you’ll also love the conversations we had with Aviva Romm, MD about how hormones control health, and what we can do about it.Check out our offerings & partners: My New Book SparkedMy New Podcast SPARKEDVisit Our Sponsor Page For a Complete List of Vanity URLs & Discount Codes.Peloton: Access high-energy workouts, instantly. Discover Peloton: streaming fitness classes to you live and on-demand. Try Peloton risk-free with a 30 Day Home Trial. New Members only. Not available in remote locations. See additional terms at www.onepeloton.com/home-trial. Hosted on Acast. See acast.com/privacy for more information.

And it seemed to me that trying to figure out why people don't live longer than they do was something no one else was really doing in a rigorous way. And I'm not so much worried about my own mortality. Some people think I'm worried about dying. I'm not really worried about that. But I am worried about not doing the best I can for humanity. I'm a real fan of humans, and I want to leave this world a better place than I found it. Okay, so question for you. What if you could slow down time? What if you could stop or even reverse the aging process? What if you could live not just longer, but better, extending and even potentially expanding your physical and mental health

and well-being, staving off decline or illness? Is any of that really possible? And what does the latest science have to say about it? That is what we're talking about with today's guest, David Sinclair. So David is a worldwide leader in aging research. He's a professor in the Department of Genetics and co-director of the Paul F. Glenn Center for Biology of Aging Research at Harvard Medical School. And he's best known for his work on genes and small molecules that delay aging, including sirtuin genes and resveratrol and its precursors. And we get into all of this in a lot of detail.

He's published over 170 scientific studies, is the co-inventor of over 50 patents, and co-founded 14 biotech companies in the area of aging, diabetes, fertility, cancer, biodefense, his book Lifespan, Why We Age and Why We Don't Have To explores what we get wrong about aging and how to approach it differently. And his podcast Lifespan also explores healthy aging and how to live not just longer, but more well as well. So excited to share this best of conversation with you. I'm Jonathan Fields, and this is Good Life Project.

Mayday, mayday. We've been compromised. The pilot's a hitman. I knew you were going to be fun. January 24th. Tell me how to fly this thing. Mark Wahlberg. You know what the difference between me and you is?

You're going to die. Don't shoot him. We need him. Y'all need a pilot. The Apple Watch Series 10 is here. It has the biggest display ever. It's also the thinnest Apple Watch ever, making it even more comfortable on your wrist,

whether you're running, swimming, or sleeping. And it's the fastest-charging Apple Watch, getting you 8 hours of charge in just 15 minutes. The Apple Watch Series X, available for the first time in glossy jet black aluminum. Compared to previous generations, iPhone XS or later required, charge time and actual results will vary. I'm curious about a number of different things, and I figure we'll touch down in a few different areas. I guess one of my early fascinations is I'm always curious about people's personal choices about how they want to invest their energy in a body of work for their life. And so I'm curious about you.

You could have taken any number of paths when you decide to enter medicine. Why aging? Well, I like a challenge. I tend to go the opposite direction of anyone else. If everyone's going off and studying computer science, I'll avoid that. And it seemed to me that trying to figure out why people don't live longer than they do was something no one else was really doing in a rigorous way. But really, it goes back to when I was four years old. my grandmother was telling me the

truth. She was a very honest and brutal person who raised me. And she said, David, your cat's going to die. I think I was asking about my cat's health. Yeah, it's going to die. And I went, die? What does that mean? I was gone forever. You'll never see it again. Really? Yeah, that's going to happen to your parents. It's going to happen to me. It's going to happen to you. For a four-year-old, that's a real shock because I'd been raised on Disney movies and no one dies in a Disney movie. And I think that happens to everybody around the age of four or five. But by the age of about seven to nine, we forget about it. And we have to, because if we're constantly worried about dying, it's pretty stressful. So we've evolved coping mechanisms and we typically don't think about aging till much later in life, 50,

60, we start to see the end of life and we see our parents, grandparents pass away. But I've since, I think, thanks to my grandmother, I've been unable to get that out of my mind. And I'm not so much worried about my own mortality. Some people think I'm worried about dying. Anyone who's seen me drive my Tesla knows I'm not really worried about that. But I am worried about not doing the best I can for humanity. I'm a real fan of humans. And I want to leave this world a better place than I found it. When you start to go down this road, I mean, it's interesting because to a certain extent also, you choose a focus, an area to focus,

that I think a lot of people actually don't consider a problem, but rather just a fact. And that is largely unchangeable. I think like a lot of the old paradigm is, well, this is what happens. We get old, systems fail, you know, like things start to melt down. It seems like you hear,

well, no, they died of old age. Yeah. And it's just kind of assuming, that's just the state of things. It's not a disease to be fixed or cured. That's just what happens. Well, we used to say that about cancer and heart disease, and we don't accept those things anymore.

Cancer is just as natural as aging. So why do we rail against cancer and infectious disease? We're trying to combat that right now. Why don't we say, oh, that's natural. Let nature take its course. The same with aging. I think the world is in a stupor. It doesn't understand that what's causing most diseases on the planet, from heart disease to cancer to Alzheimer's, is aging itself. Now, doctors are trained to treat diseases, so they don't think about really what's causing them typically. They treat the symptoms. But the driver of what's pushing us off the cliff is really the aging process. It turns out if we stay young and healthy and resilient, we wouldn't get these diseases in the first place. Describe for me, when we talk about aging, what's the current

understanding? What's sort of like the current slash old model for understanding what this is? Oh, the old model or the current model? Well, tell me what the distinction is. The reason I wrote the book mainly is that the science has gone through massive leaps and bounds to a point where we think we understand what's driving aging. And the good news is we can actually do something about it. Now, if you can't do anything about it, like people 200 years ago, when it came to an infection, they basically accepted it. Go home, pack your things, you're going to die, cut the limb off, maybe that'll help. Once you can do something about it, then you can actually contemplate addressing it. Same with aging. The science is at a point now that we understand, we think, not just how to slow it down, but actually totally reset the body to be young

again. And if you've seen the kind of data that I've seen from labs around the world, including my own at Harvard, you have this new sense of optimism that we can actually do something about this process. Not that we're going to live forever or even 200 years, but we are entering a world where we don't have to accept aging as natural. And the other thing that we've seen, which is really empowering, is that only 20% of our lifespan is genetic and the rest is up to how we live our lives. Can you deconstruct that a little bit? Well, there's a study that was done in Denmark on twins, identical twins. And these twins were leading to very different lifestyles.

You know, one's smoking and eating hamburgers and the other one's eating a plant-based diet and exercising, to take extreme examples. And those twins were living dramatically different lives. So clearly it's not all in the genes and the number is 20% genetic and 80% something else. And what I've put forth in the book is a new theory on why we age. And that is, it's called the information theory of aging. And what we lose over time is actually information that we're given as youngsters. It's called epigenetic information. And we lose that over time if we don't take care of our body, if we don't do all the right things, which I list in my book on page 304 if people are interested. Then we lose that information. Now you might be saying, Jonathan, you're looking at me like,

what's this information? The information isn't Now you might be saying, Jonathan, you're looking at me like, what's this information? The information isn't what you might think. The information is in two forms in the body. One is genetic. And that's surprisingly largely intact in our bodies even when we're all genetic. The DNA information is there. It's this other type of information that reads the DNA,

that tells a cell, you should be a nerve cell, you should be a nerve cell, you should be a liver cell. That's the epigenetic information, much in the same way that a DVD, to use an old device, would be the genome and the reader of the DVD would be the epigenome. Or another way to think of it would be the genome is the piano and the pianist is the epigenome, playing the notes. And then aging is the epigenome playing the notes. And then aging is a simply a demented pianist. And what I'm excited about is that we can keep the pianist playing beautiful music for longer, doing just the right things in our life.

But also we've just discovered, and we're just about to publish, that you can bring in a new pianist and reset the system like a software reboot. And if that's true, then all bets are off. Then we may be able to do things that we've only dreamed of. We already know there are animals on the planet that can regenerate whole limbs and even be immortal like a jellyfish. And I think we're finally tapping into those mechanisms for our own body. It's the Holy Grail, right? And yet at the same time, that's the Holy Grail. And then, and I want to actually sort of go into that a lot more with you, but zooming the lens out, you know, there are also these sort of bigger ethical and moral questions

that, well, what if humans actually could live, maybe not indefinitely. I read somewhere once in a study that even if your body actually could stay the same age at somewhere around 300 years old, your likelihood of death is 100% through accidental means. So there's sort of like this cutoff almost anywhere, like you're going to get, you know, like something's going to happen to you. But, you know, if in fact we can do this, if we can expand lifespan, double it maybe,

what is then the effect on society? What is the effect on the planet? You know, and all these sort of like bigger conversations. Yeah, so the last third of my book covers this. Because if I'm going to work on this, I have to think about its implications. That's my responsibility. The good news is that this isn't going to happen tomorrow. We cannot stop aging tomorrow.

You know, I'm optimistic, but I'm not that optimistic. And society will evolve similar to how we adapted to kids not dying in childbirth with their mothers and limbs not being amputated anymore. We adapt. And I use the analogy of old London in 1830, where people were dying in droves from cholera. And in those days, London was overpopulated. There's a lot of pollution. Fast forward now to the city where there's three times as many people and people are living utopian dreams in that city with restaurants and shops and no disease, except for maybe recently. That is the future that I think we will have, which is that if we live longer and relatively free of disease, let's say we can all

make it to 100, even let's say 150, if we really dream without getting cancer and heart disease, let's say we can all make it to 100, even let's say 150, if we really dream, without getting cancer and heart disease, we're going to live in a world where, yeah, it will be different. We can't retire at 65 anymore. It's just not enough young people to take care of the bank accounts of the older. But it's a trade-off, right? Would you rather get cancer at 70 and die a horrible death over the next 10 years? Or would you rather have a world where we have to be more conservative with resources and perhaps take greater care of the world around us and exchange, not worry about getting these diseases until much later?

Well, hopefully we reach a point where we get to grapple with that. You know, when we talk about aging also, so you talk about the loss of information. How does that manifest physically in the process of what actually unfolds in the body? Yeah, so we typically use mice to check this out. They don't live as long as humans, so we can go a bit faster. And we can create aging. We can speed it up. We can also slow it down and reverse it. And we've been able to disrupt the epigenome in a way that speeds up the aging process

in all the tissues, gray hair, wrinkled skin, and all the good stuff that comes with aging. Those mice become fragile. But we can also now reset the system and get the epigenome to go back to the way it was there's information there's a backup of that information somewhere we haven't found exactly where it is but we know how to tap it in using a special gene therapy that we've discovered and when we do that we get us amazing some amazing things so we can take old mice that have just aged naturally and become blind, like a human would, and we can give the gene therapy in their eye and they get their vision back, just like they were young again.

Now, those sorts of things give me, well, a lot of optimism, but also some pause to think, what is the future going to look like? If we can do that to the eye, can we reset the body, the epigenome of the entire body? And how many times can we do that? Now we've done it once in a mouse. It looks to be very safe. We haven't seen any evidence of increased cancer or illness. These mice are quite happy, especially even if we give it in the whole body, it doesn't hurt them. And of course, safety first, right? We don't want to cause harm. But imagine if you could reset more than once. You reset your body and go back 20 years and then you age out 20 years and go back and reset again. That would be

an incredible future, but also one that's kind of scary because we're not used to thinking about life that way. Yeah. I mean, all the times that you've said, if I'd only known what I know now when I was 20 or 30, be able to sort of like have that physical and emotional capacity at this age. And you're effectively saying that there may be a future where you can more or less do that. Yeah, and it raises really interesting questions about biology. So one question would be if you reset the age of the entire brain, so we've just done the optic nerve, but the brain is very similar stuff.

What happens to the brain? Does Alzheimer's go away if you make the brain young again? I'm betting that it will. But what happens to memories? Do you retain memories and wisdom, or do you lose it? And I'm hypothesizing, betting, as a scientist, that you will retain your memories. In fact, you may even recover lost memories, because your nerves will now function better. But it is an interesting question, right? Because if memory is stored in some massive complex, you know, like neuronal

set of connections and in some way, shape or form, the reset has a risk of altering that in some way. Right, right. We'll see. Maybe even your emotions will go back to being immature. We don't know, but we're testing that right now. Yeah, I mean, because some of, sure, there's some things that you would like to get back, but also there's a seasoning, there's a wisdom, there's all these things that took time to develop

that you don't want to reset along with it. And it's fascinating. When we talk about aging, how are we, how do we measure that these days? Because I think, you know, people think chronological age, oh, you know, I'm 54, boom, that's my age. But in fact, it's much more nuanced and maybe in fact, there are much better markers for this. There are, and they're brand new systems. So the epigenome is directed in part by what are called DNA methylation. So that's just a complex way of saying chemicals that get added to your DNA. And we can read those with a machine that's as big as a Snickers bar in the lab. It's

not that complicated, it sounds it, but it's not. Any high school student can do this. So I could take, Jonathan, I could take your DNA today, a swab of your mouth, and in a couple of days come back and tell you exactly how old you are. Not how old you are based on birthday candles, but biologically, are you above or below the average human for your age? And if you've taken care of yourself, then you should be under that line and younger and vice versa. If you've smoked and not exercised and eaten a bunch of fat and become obese, you are typically older than your actual age for an average human. And that's good and bad news. The bad news is that you might be older than you think you are. But the good news is that

aging, as I mentioned, is malleable. You can take your age and slow it down and possibly even reverse aspects of your age just by changing certain things in your lifestyle, which we should talk about. And these are changes that I've made in my life and my family. We do special things to try to prolong health. But the fact that you can get a mathematical now readout of your true age is revolutionary. It tells us, first of all, that the epigenome probably is linked to aging and that this information theory is probably right, not proven, but indicated. And it also says that we can much more quickly test interventions. In other words, instead of waiting 40 years to see if taking supplement X works, why don't we just test it

for a year or two and see if your clock goes back? And now we're at that point. A lot of folks I've been speaking to are, I've been focusing on telomeres, measuring telomere length. And based on the assumption that they start to shrink as you age

and that if they're longer than the average person, your age, that in fact, you know, similarly, you're actually sort of like, by telomere, you know, like measurement younger than your chronological age. How, is that right? Is that not? Is that being replaced by this new metric?

Well, so the information theory of aging attempts to explain all of the changes that occur with age, including telomere shortening. So there are about eight or nine, depending on who you ask, what we call hallmarks of aging. Telomere shortening is one of those. So others, people might be curious, are things like loss of stem cells, mitochondrial dysfunction, nutrient regulation, loss of what's called proteostasis ability to renew your proteins. These hallmarks of aging are considered separate entities right now. They're drawn as a pie chart by scientists. But what I'm proposing is that there's a unifying cause that leads to all of these, including telomere shortening. And it turns out that

the proteins that we study, they have a name called sirtuins. There's seven different flavors of them, types in the body. At least two of them are protecting the ends of chromosomes, the telomeres. And so in my theory, I can explain how this is all linked together. And the loss of information in the body includes the shortening of the telomeres. So that's basically one contributor, one component, these different things. And so it's almost like your measure becomes the meta marker. Yeah, that's exactly right. And telomeres are an okay measure of your age, but it turns out they're much more variable and they can get longer, they can get shorter. We've actually

learned that they're not as accurate as the actual DNA methylation clock that I was describing, which is also known as the Horvath clock, named after my friend Steve Horvath, who discovered it. You also, you brought up as one of those components, mitochondria, mitochondrial function, which, you know, immediately my brain goes back to middle school, like the power plant of the cell. And this is where we get our energy. This is where ATP gets, you know, goes out into the body. And, but it seems like there's also been a lot of focus on that similar to telomeres on mitochondria and their dysfunction over time as a real contributor to, to every element of aging. So it, if it folds into this metamarker is, I guess I'm curious, am I getting it right in terms of the way I'm describing mitochondria? And I'm curious about how that really contributes to the experience of aging.

Yeah, no doubt mitochondria decline with aging. And what we've discovered is that the reason they decline mainly is that the epigenome isn't preserved. The information in the body to turn on the right genes isn't preserved. And what we've discovered actually in my lab is that it's very easy to reverse mitochondrial dysfunction and decay during aging. We published a paper a few years ago, just by triggering a pathway that we work on, getting these sirtuins to work better, the mitochondria could be totally rejuvenated. So again, we take a mouse, it's old, it's got mitochondria that are producing much less energy, less ATP.

By the old idea about aging, which is it's all about free radical damage and mutations, that should be irreversible, right? As you lose information of your DNA, you're not going to get it back. Like if you break off a piece of a DVD, it's not going to come back. You smash a piano, it's not going to play music. But I'm saying, no, the piano is intact. The DVD is still there. You just need to read it again. So in our treatment, in our paper, we showed that within just a few days, we can rejuvenate the mitochondria back to being young again, just by tweaking the epigenome. And that tells me that the DNA is intact, largely. It's just the cells forget how to read that DNA.

So it's not so much that the CD isn't scratched, it's the reader that's having trouble. Well, it's both. They're both. Same effect. I think a scratched CD is a good analogy, actually, that if you can just polish the CD, you'll be able to read the music underneath. And that's what our methods are doing, actually. It's just allowing that laser beam to hit the right pits in the silver lining of a CD. For any young people listening, CDs are these things we use to put music on, and you could

fit about three photos on there. It's really amazing technology. Once upon a time, they replaced floppy disks and computers for a hot minute. The Apple Watch Series 10 is here. It has the biggest display ever. It's also the thinnest Apple Watch ever, making it even more comfortable on your wrist, whether you're running, swimming, or sleeping. And it's the fastest charging Apple Watch, getting you eight hours of charge in just 15 minutes. The Apple Watch Series X. Available for the first time in glossy jet black aluminum. Compared to previous generations, iPhone XS or later required,

charge time and actual results will vary. Mayday, mayday. We've been compromised. The pilot's a hitman. I knew you were going to be fun. On January 24th. Tell me how to fly this thing. Mark Wahlberg. You know what the difference between me and you is?

You're gonna die. Don't shoot him, we need him! Y'all need a pilot? Flight Risk. It's interesting, and you know, epigenetics first came into my orbit when I, and they were described as, okay, so you have your DNA, which essentially is like

the code which is relatively fixed, except for damage that can happen to it over time which degrades it but then there's this you know is are they is there's the expression of it which actually is what affects like us and that's the epigenome right right and then you know whether they're turned on or turned off whatever the the state is, effectively, is that overlay. Right. That's actually the most important information in our bodies is how to read the right genes at the right time and make sure the cells are functional. And so what we've found actually is that if you can reset the epigenome, cells that are dysfunctional and causing disease such as blindness, the body heals itself, comes back and also resets all of those defects. So mitochondria rejuvenated, the telomeres come back in their length. All of those things that we think are actual causes of aging, we think are stemming from this loss of the epigenetic information that allows the genes

to be read. We should have known this a long time ago, really. If you look at the evidence, ever since the first frog was cloned from a tadpole, and now we have dogs and sheep and cats that live normal lifespans. Barbara Streisand cloned her to two dogs. These animals are healthy. So what that says is that adult cells have all the information to be immortal. You just need to tell the cells how to read those genes again. So I guess what's popping into my head also then is, why do we lose this information? Well, that's been what we've been working on for 20 years now. And what we think is going on is that the proteins that control which genes should be on and off become distracted by

other things. One of the main distractions that causes them to leave their posts. So I don't know if I want to get into how genes are regulated, but essentially there are proteins that sit on DNA and tell it to either be shut off, which is what we study. The sirtuins are gene silencing proteins. There are also proteins that turn genes on. And part of that process is DNA packaging. If you bundle up DNA really tightly, like a hose reel, it doesn't get turned on. Whereas if you open it up, pull out the hose reel, now the genes tend to come on. Those proteins are very important because they tell genes whether they're on or off,

but those proteins have other functions. For instance, the sirtuins that we work on, three of them at least out of seven, need to repair broken DNA. So if you break your DNA, which is happening all the time in our body, a trillion times in our bodies a day, those proteins get distracted. They have to go off and they repair the DNA. But they also have to find their way back to where they came from, to Gene X from earlier.

Similar to when Hurricane Sandy destroyed the South and the Army Corps of Engineers had to go off and repair those things, but they had to find their way back home and pay bills and mow the lawn or whatever. And if that game of, call it a game of ping pong, of moving things out, coming back, what I'm saying is that over time that doesn't reset. So effectively there's too much work to do for too few of these things, too few. So they become overwhelmed and you lose, you either lose adequate DNA repair or the sort of like the epigenetic effect of keeping things young and healthy. Exactly. That's what's going on.

And that's why if we stimulate the sirtuins, if we make more of them by leading a healthy lifestyle or eating the right foods or even taking some supplements that we think might help, then what happens is we give the sirtuins enough energy to do both activities at the same time. What is it? So you said there's DNA damage going on in our body 20 times a day. What's that caused by in the first place? I mean, on the one hand, yes, let's supercharge our sirtuins so that they can actually do both jobs. What's actually leading to the DNA damage? And is there a way to lessen that or slow it down that would also help the entire situation? Well, the good news is the sirtuins are sensing the cellular environment.

When they think that the body is under threat of survival, they'll be more active. And you can do that a few ways. You can encourage the body to make more protein, sirtuin protein, and you can do that by being hungry or exercising. And there are two other ways to turn on sirtuins. One is to give them more fuel. Actually, they're enzymes. They need fuel to maintain the epigenome.

And that fuel comes in the form of a little molecule called NAD, which our body makes, but actually makes less as we get older. And then the third way is that there are molecules produced by our body or in our food that we eat that also are like the accelerator on the sirtuins and rev them up. Let's walk through some of those. But first you also mentioned, I guess, food and exercise kind of slipped in there, but food in a particular way. And I guess this has been a really hot trend over the last couple of years, is the idea of fasting or intermittent fasting. There are all these different variations of these things.

And I know people have pointed to different mechanisms why they think it's helping in different ways, whether it's weight loss, reducing inflammation. But you're kind of suggesting something different happening in relation to that. Right. Again, it's putting the body in a state of fear, fear that food's going to run out. And now you don't want to starve. You don't want to have malnutrition. But if you are hungry for part of the day or part of the week, your body biologically says, holy crap, I could run out of food here.

I need to build survival mechanisms. And so it ends up doing that. And one of the ways it does that is through these sirtuin enzymes that preserve the epigenome, but also help repair things, repair DNA, fix the proteins. Now, when you're hungry, a few things happen that are really good in the short run. You will raise your NAD levels, so sirtuins have more fuel. You'll make more sirtuins themselves, so there's more enzymes around to do the job. You'll also break down fat. And what we've just learned, thanks to another lab that published this a month ago, is that the breakdown of fat produces oleic acid,

which is a monounsaturated fatty acid. Oleic acid is an activator, one of these accelerator pedals of the sirtuin. Lake acid may be familiar to people who study food. You get it also from, guess what, olive oil, avocados. All the things that we've learned seem to correlate with better health. So what I'm saying is when you're hungry, you're activating your sirtuin defenses against aging and disease in many different ways. So maybe that's actually, maybe not like the entirety of the underlying mechanism, but a healthy part of it when people talk about the benefits of some version of fasting.

Well, it's a large part of it. And some of the evidence comes from work that we've done where we can take molecules that accelerate this sirtuin. So one is resveratrol from red wine, which most people have heard our lab work on. Now, if we give a mouse that's on a Western diet, it's obese, it's going to live a short lifespan like a lot of us tend to do with our lives, and we just give it resveratrol, that's the only thing we've changed in its diet, we mix it in with the food, their bodies are as healthy and as long-lived as a mouse that eats a healthy lean diet. What does that tell me? It tells me that with a small intervention, just by activating the sirtuins, you can mimic fasting. And it's probably true, and this is now more speculation because we haven't done the experiment,

but when you eat olive oil or take a lake acid in, you're mimicking fasting as though your body is degrading your fat. And it perfectly explains why this Mediterranean diet is so healthy. Now, I'm not saying it's everything. Of course, there's no such thing as one thing does everything. But I think a large part of it is correct, is that when you're fasting, it's not that you have less inflammation and that's all that happens, you have less free radicals. What's happening is that you're turning on these defenses in your body,

partly through these sirtuins, and you get less inflammation because of these defenses. If we knock out the SIRT1 gene or some of these SIRT2 genes, which we can do in a mouse, and then we fast them or give them caloric restriction, then the benefits go away. You need these genes for it to work. So clearly then that is a huge part of the mechanism, if not the mechanism. Right. So I get a little frustrated, but I'm a little too busy to get too frustrated with this antioxidant idea. Oh, that if we just take these molecules that are antioxidants, that's the whole story. That's 1980s science.

We've moved beyond all of that. Well, I mean, because I think a lot of people still do use the word antioxidant and think about it. You know, that was, you know,

your body, I think there's a lot of the original theory on aging. Your body's experiencing oxidative stress. You're essentially rusting from the inside out, and there are these things that will stop the process or fight it and battle free radicals. But you're saying that's really not the paradigm. No, no. I mean, there's a lot of attempts to use antioxidants to mop up free radicals

and extend the lifespan of lab animals, and almost all of those have been failures. It's a real disappointment. We learned that in the 1990s, but I think the whole antioxidant story is a good marketing ploy. There's billions of dollars of drinks and food sold under that premise, but it's not true. We actually need free radicals for a lot of biology, for the immune system. And there's a theory, I guess it's kind of not theory anymore. It's called mitochondria, which is that the mitochondria need to produce free radicals for longevity benefits. We study in the field, these nematode worms, because they only live for a few weeks. If you make a worm long lived by knocking out, say it's insulin signaling pathway, if you then give it a free radical quencher, an antioxidant,

it lives shorter. And exercise needs free radicals. If you mop up free radicals, you're not going to have the benefits as much of exercise. So really, and the other thing I want to tell you, Jonathan, is that if you take resveratrol, which some people call an quote-unquote antioxidant, it's a very weak antioxidant, by the way,

we can chemically modify resveratrol so it's not an antioxidant, but it still activates our sirtuin genes, enzymes. Then it still gives the health benefits, even though it's no longer an antioxidant. Yeah. So clearly that's not the pathway there. I mean, what's fascinating about the idea of taking something, on the one hand, it makes it so much easier and accessible to a lot of people because we've all been told for generations, you know, it's like watch what you eat and move your body. Like exercise is the healthiest thing that you can do. It's like the best medicine out there. And in fact, I think when you look at a lot of the research, you see a tremendous benefit from staying active on a regular basis. I have this sort of like mixed feeling going on where it's like on the one hand, if part of the research you're showing now is saying that we can get nearly identical benefits from essentially taking something that we can from exercise and from fasting, which a lot of people experience as

not pleasant and huge compliance issues. So on the one hand, yes, it solves that. But on the other hand, aren't there also some benefits of things like, you know, like reasons to continue to do those things? Does that essentially give people permission to just never move their bodies again? It doesn't. And that's the reason that even though I take resveratrol, I'm still exercising. What we find in our studies is that, yeah, you get some benefits from exercise. You get benefits from fasting.

You get benefits from taking resveratrol and raising your NAD levels if you're a mouse, probably a human too. But when you combine them all, that's when you get the biggest bang for the buck. So it's not an excuse to just sit around and pop a pill at all. In fact, if you want to be healthy in your 90s, you've got to do all those things, I think, or at least many of them. For instance, so we can raise NAD levels in a mouse, an old mouse, and it can run like a young mouse. But if we take that same mouse and we exercise it and raise NAD, then it's double the effect. And so I'm not trying to say it's an excuse to just sit around and watch movies and eat popcorn all day. Not at all. Right. So does it have the potential to reverse? Because part of the aging experience is a sort of a progressive loss of muscle mass and bone density. Will it act on a level where it actually has the potential to stop and even reverse those?

Well, so it was pretty easy to reverse the loss of blood flow in the muscle and the energy in the muscle. So the ATP goes back up. We haven't found that it's easy to reverse muscle loss. That's been a struggle for a lot of scientists. We can a little bit. And so we're working with NASA funding actually to try and preserve muscle mass and mimic exercise for astronauts so they don't have to spend three hours on a treadmill every day. But it's really hard. That aspect is harder than pretty much everything except maybe hair loss and

hair growing. Those are the two tough ones. But here's the good news is that it doesn't take much to preserve muscle mass actually. So I spend an hour working out a week. I'd like to do more, but I don't have time. And that for me is maintaining my muscle mass. I'm now in my fifties, which it's extremely important. I can't emphasize enough to people who are listening, please work out, please make sure that your legs, your hips stay strong, especially after 50, because the number of people who die from a fall is, it's really scary. Every 19 minutes, an American falls over and breaks a bone in their old age, and they don't recover, and that leads to death eventually. My grandmother had the same thing.

She tripped on a carpet in her 80s and never recovered. So please keep the strength up. You've got to do that. And then also it's very important to do high-intensity exercise. Not a lot. You don't have to run marathons. Just 15 minutes a week is certainly better than nothing. I've also, now I've got a standing desk, which has helped maintain my strength of my hips too. And writing this book took a couple

of years of sitting down. And by the end of it, I'll tell you, I could not walk properly. I couldn't run. I had what's called a piriformis muscle cramp. It's the syndrome. It's that muscle that runs through the hole in your hips. It took me a year to recover from that. And I'm never going to go back to that. So I'm going to stand up whenever I write. Yeah, it's funny.

I've sort of been altering a lot of things also. I go back and forth between standing desk and sitting because I spent a lot of time writing also. And I'm about to start into the whole new project. And just like you have felt the profound and negative effect of doing that. And I feel like it gets harder and harder to recover from that the older you get. Now, maybe if I'm actually supplementing differently,

behaving differently, but even so, I think just the physical activity part of it, it takes longer to sort of recoup what I've lost in terms of mobility, muscle mass, and loss of pain. I'm really curious about this idea, though, that you are able to effectively reactivate so many of these contributors to what we would coin aging, but muscle loss is still so elusive. I'm just curious why. What's going on there? Well, we haven't reset the epigenome in the muscle yet. We're going to do that. That's one experiment that's ongoing in my lab. My suspicion is that once we reactivate that and reset those cells, then they'll respond to exercise and walking and rebuild those muscles. But until we do that,

I think that that's the obstacle, right? So I've got a couple of different approaches in my toolbox. One is molecules that turn on the body's defenses and reverse some aspects of aging, mitochondrial function, blood flow, all of that was pretty easy. The hard part is you're still dealing with cells that don't read the CD properly. And so it's not perfect, right? It still scratches there. So my second thing in my toolbox, just from the last couple of years, which I talk about in the book, and actually I wrote the book while we're making these discoveries. So the readers get the feeling of what it's like to make them. Resetting the epigenome, I think, it changes everything.

It means that those cells won't just feel young. They'll actually be young, literally. And if I go in and measure the biological age of those cells, I won't be able to tell that they're old anymore. And then they will, I predict, build muscle like, you know, you're a 12-year-old again. I mean, what I mean, powerful in the context of just reversing the loss that we've always assumed is just kind of like what happens, you know, like you hit your mid years and then every year you, you know, the average person I think loses a half pound of muscle mass or something like that. But also in the context of zooming the lens out to diseases that in some way involve muscle loss and muscle wasting. If there's a, now I realize that some of those diseases also are neurological in basis and it's, you know, it's the circuitry that actually stops the contraction of muscle, which leads to the

accelerated movement. But if you could potentially reverse all of that, I mean, the implications are pretty stunning, not just to aging, but to that, things like that as well. Yeah. So I was excited when we were able to make old mice run on a treadmill 50% further. In fact, they ran so far, the treadmill stopped working because mice weren't supposed to run that far. What that led me to think was that the big problem with frailty in the elderly is that they stop exercising. A, they don't get the gains from it, but B, they don't feel like they've got the energy. And often it's too late once you become frail. But if you could reverse that and get people out of their chairs and out of their beds to move again, you know, you'd get the benefits of exercise again. But that does remind me to say that you

don't want to get to that point if you can help it. It's all coming, but you can put it off. So my father has to exercise three times a week to maintain what I can do with one bout of exercise, and he's 80. So to your point, it gets harder and harder as you get older, so start early so that you don't have to try to regain it. You just want to maintain it at least. Yeah, but I have actually long agreed with you about this idea of this or like the the exercise cart before the frailty horse you know it sort of you know does the fact that we become old you know like stop us from being able to move our body or the fact that we stop moving our body actually accelerate the process of being old which accelerates the process of muscle loss which accelerates us not being able to move. And it's actually, and it just becomes this destructive cycle that becomes, I guess, I

would imagine at a certain point, well, actually, let me not imagine this. Before this conversation, I would imagine at a certain point, you know, like the average person in that spin cycle would hit a tipping point where you really can't go back. Is that true? And if so, do you think the work that you're doing and other people are doing in the world may in fact change that? Yeah, it'll certainly help get people back on the cycle,

figuratively and literally. But I've seen some incredible things on social media where elderly, old, frail, obese elderly people, male and female, have changed their lives and lost the weight and gone to the gym and become essentially fit, happy people again. So I would say it's almost never too late. But the longer you leave it, the harder it is. Yeah. The Apple Watch Series 10 is here.

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You know what the difference between me and you is? You're going to die. Don't shoot him, we need him. Y'all need a pilot. Flight risk. I want to jump back to, you referenced Rizvair Chal a number of times, and you're doing a lot of research on this, and it sounds like it's incredible. There's also research out there, at least that I've seen, and I'd love your lens on this, that shows that, and maybe I'm not reading this right, it's not always beneficial that there's a

sort of a time dose effect where it can be incredibly beneficial, but also consumed the wrong way becomes destructive, pro-oxidative, leads to the increase of cancer cells rather than the decrease of them. So it seems like it's not, you know, am I reading that right? Well, so resveratrol isn't known to cause cancer. There's a theory out there that raising an ED could promote cancer. And that came out of a misinterpreted study from University of Washington. Unfortunately, the misinterpretation went viral and Scientific American wrote about it. And I guess now that we're down that rabbit hole, the study showed that if you knock down the NAD levels in cancer cells, they don't grow as well. There's a brain cancer in a mouse, which means

that cancer cells need NAD. It doesn't mean if you raise NAD, cancer cells are going to grow more. It's like saying, if you take the wheels off a car, it won't move. But if you put 20 wheels on a car, it'll go faster. That's ridiculous. So I've done a lot of work, both in mouse and human studies now. I wouldn't say I know everything. We have much more work to do. But I haven't seen anything

that makes me concerned that what I'm doing or my father is doing would cause cancer. Obviously, I wouldn't do it if I thought that. But again, I'm not saying it's all risk-free either. We're still learning. We're all born probably one or two generations too early for us to know everything. But if we wait another one or two generations, we're all dead. So you've got to take some risks and, you know, it's a calculated risk. Raising an AD does seem to actually slow down cancer, we found in, at least in mouse models. And the fact that we're now in humans and done a lot of safety studies, and these are separate groups from me. In hospitals, they've reviewed all the literature.

If they're allowing these trials to go forward, I think for now, there isn't reason to panic about it. Yeah. Are you seeing, now that you've made the jump from mouse trials to human trials, are you seeing the outcomes translate in a pretty linear way? Are you seeing really similar things happen in humans that you saw in the mouse?

Well, what I can say is we're seeing that it's possible to raise the NAD levels in humans a lot, twofold or more, which is what you'd get if you're a marathon runner or something like that. But we don't know yet if we can recapitulate these other things like improvements in endurance and mitochondrial activity. So that we should know by the end of this year. Oh, wow. It's going quickly, the research. Yeah, we just got FDA approval to go into patients

to actually test whether they work or not. But actually we're not only testing older people, we're also testing rare diseases. For instance, Friedreich's ataxia is a mitochondrial-related disease. I had somebody on the podcast who has lived with that. Really? Yeah. Okay. Yeah. So that's the other thing about aging research is that

often we underestimate the value of the research. I know aging is important, no question. But also, we're talking about boosting the body's defenses against frailty and injury and diseases beyond typical ones. Friedrich's atexia is a good example. Viral infections, if you can boost the body's immunity, then you can survive that as well. In this day and age, obviously, big benefits there. Yeah, yeah.

I mean, it's mostly the frail and the elderly that are succumbing to coronavirus. If we could magically or even pharmaceutically make old people young, even temporarily while they were sick, then they wouldn't die and we wouldn't have this crisis. As you're speaking, I'm noticing also you're waving around your hand and there's a little silver ring on it. And I have this the stealth version of what i think is the same thing is that a or a sleep ring uh it is um which which makes me curious also about the contribution of sleep to everything that we're talking about yeah so nad uh and so two ones also control the sleep wake cycle that was uh it's well proven and so your nad levels go up and down throughout the day. And if you take an NAD booster late at night, you probably won't sleep very well.

Conversely, as we get older, we have less NAD and our sleep-wake cycle gets disturbed. So elderly people don't sleep well and jet lag is not good for us either. So think of longevity and sleep as being intimately connected through this mechanism that I'm talking about. And if you're not going to sleep well, then you're not going to defend your body against aging long term. If you disrupt the sleep of a rat for a couple of weeks, it'll get diabetes. It's that potent. Oh, wow. Yeah. So it's very important to get a good night's sleep, particularly the deep sleep.

Yeah. And you're saying NAD potentially plays a role in the quality of your sleep. Yeah, that's agreed upon by scientists. And it was a discovery about 10 years ago. And so actually I find that, this is anecdotally though, that if I take an NAD boosting molecule when I arrive in Australia, I don't get jet lag. So interesting, too, because as you referenced, if the average person gets less and less sleep with every decade of their life, and at the same time, there's a fairly similar relationship to reduction in NAD over that same window. I guess maybe there's not

research to prove it, but there's an interesting correlation there, whether it's causation or not. Yeah. Well, again, it's one of these negative feedback, horrible cycles that you don't want to get on. We know that if we disrupt the sirtuin gene, number one, sirtuin one, the mice will have disrupted sleep cycles and they'll get premature aspects of aging so it's very clearly linked together but yeah it could be that that the loss of nad leads to the lack of sleep which makes things worse so yeah you just don't want to go anywhere near that stage if you can help it yeah and so many people listening to this right now are thinking to themselves but that's just my life.

Yeah, it used to be my life. I was an insomniac. It was horrible. I was almost suicidal. It was that bad. You can change your life. At least I've found I have. By looking at the ring, changing things before I go to sleep, during sleep, how I sleep, what I wear during sleep, I've been able to get a good night's sleep most nights. And I'll give you some of the ideas. If you want the cheat sheet, go to page three or four of the book. But some of the things that, you know, blue light blocking is important. Don't be reading your emails till late or watching TV without those blue light blocking glasses. What else? I don't drink a lot of alcohol straight before sleep or a large meal especially meat it's hard to sleep with that in your stomach i do take melatonin a little bit of melatonin and there's l-theanine which has helped me as well yeah i mean it's interesting also there's

i'm familiar with those and and um i've also looked at over over the years the relationship between exercise and and sleep quality and it seems over the years the relationship between exercise and sleep quality. And it seems like the exercise, the relationship there is really mixed and also may really depend on the nature of exercise, the time of day, and be specific to gender. Yeah, well, I find that if I exercise late, I don't sleep. Yeah, pretty much the same way I've experimented. There's another chemical molecule that you referenced that is really interesting, NMN. I can't remember what that actually stands for. Tell me more about this.

Yeah, so this is nicotinamide mononucleotide, and it's what the body uses to make NAD. So you can force your body to make youthful amounts of NAD by eating. I take about a gram of it per day. And so I haven't measured my NAD, but I know from looking at other people, my NAD levels might be about two times normal. And that is giving me fuel for chemical reactions in the body, and particularly the sirtuin defenses, that's one of the molecules that we gave to mice to reverse aspects of aging. That was what gave them more endurance.

And so I take that in the hope slash expectation that my body is fighting aging and will not get as old and will preserve the epigenetic information. So these sirtuins are the epigenetic regulators. And we'll have to see. I want to measure my Horvath clock. I haven't done that yet. A lot of people want me to do that. And I will.

It's just been a matter of these tests haven't been freely available till recently. Yeah. I mean, if you're taking resveratrol and NMN simultaneously and they both increase the levels of NAD, then it also, I mean, wouldn't it also become, it's sort of like compounding variables, you know, like difficult to figure out like which of these is actually having an effect or does it really matter? It does matter for me because I'm a scientist. What I do is different

than most people, though anyone can do it. I subscribe to a company that gives me blood biomarker readouts. And I've been doing that for about 12 years now. Do you mind if I mention the company? I don't have to. It's called Inside Tracker. And in full disclosure, I advise that company, but I do so because I believe in it. And what they do is that they, unlike your regular doctor, they can graph all of your biomarkers. They measure a whole bunch, 34 or so. And what I can see in my body is, first of all, how it's been changing over time. And when things go out of the range of optimal, no in your disease, but even just slightly yellow

from green, I bring them back into the green zone. And the second thing that InsideTracker does, which we found is quite beneficial and as effective as the best medicine for diabetes, type 2 diabetes, is the health recommendation. So they tell you primarily what to eat to correct imbalances. And it works for me. And so whenever I get high cholesterol or just trending up, I can bring it back down with their recommendations. And to your question, when I take a new supplement, I'm monitoring what happens. I'm not taking them all at once and hoping for the best, which is what typically we do. I know what happens to my body. And if nothing happens, I'll know. And if something good happens, I'll

know. And if something good happens, I keep taking it until otherwise informed. Yeah. I mean, it's fascinating to me, the availability, you know, to sort of on a consumer basis to track. I mean, we both referenced this ring that we're both wearing, which we actually haven't said what it is, but we're wearing a ring that essentially is a little computer

that tracks the quality of sleep and also heart rate, heart rate availability and things like that. And so you can kind of monitor and graph it over time. And it gives you a lot of interesting information. And then, you know, the ability to then do blood work and actually track biomarkers over time. You know, it's interesting. I think it's become so much more available. I know a number of different companies that let you do that. My sense is, but for the

weirdos who call themselves biohackers or scientists and just are really fascinated by this stuff. A lot of people don't take advantage of any of that. I'm in a weird place in that, you know, like we're in New York City right now and New York is actually the only state in the country that doesn't allow you access to any sort of independent labs. So I'm waiting for that hopefully to change one day, but the entire rest of the country,

and I think a lot of the world does. And I love the fact that we are gaining the ability to literally every month, if we want, check in and not just say, well, how am I feeling? But actually look at the data and see what's actually happening here. Right. We are empowered. We can look at our DNA. We can look at our biological age. We can look at our biomarkers.

That's important because we don't know if anything's working. And the analogy I put in the book is we have over 150 sensors in our cars, and we wouldn't think of driving a car without a dashboard or an alert if something was going wrong. But we know nothing about our bodies. The best we get is we go to the doctor for an annual checkup if we're not sick. And, you know, these old crappy printouts that the doctors look out and there's an asterisk if it's out of range and the doctor will say, well, you're out of range. We'll give you this medicine or whatever. That's primitive. That's 1960s, 1970s stuff. We can now move our own, well, I wouldn't say therapies, but our own knowledge into the 21st century with these

companies that are accelerating our own ability to, to know our bodies the way we know our cars. And I think in the future, we're going to think, how crazy was it that we went for an annual checkup and our doctors had no idea during the year if we really had developed a tumor or a cancer or high blood pressure or diabetes. Kids in the future will, our kids already think it's crazy that we only go to the doctor once a year. And with the ability to now measure cancer years before it actually develops with the blood tests, we're going to be alerted within a few days of developing a tumor

that there's something wrong. And that will prevent what happens now is you go to the doctor and it's often too late. Yeah, it feels like we're on the edge of a real sea change in the way that we understand what's happening in our cells, the speed at which we have information and our ability to respond to it, especially with so many conditions and diseases that dramatically limit or end life.

With a lot of them, the earlier you identify and can work with it, the better the outcome. So this gives you a lot of that. And then also, so we talked about resveratrol, we talked about NMN. In the context of NMN, that's all, I mean, dissimilar to resveratrol, it's from from what I understand, a pretty shelf-unstable substance. It is. Now, it's not going to hurt being on your kitchen shelf for a few weeks, but long-term, if I test the NMN in the lab that's sitting on the shelf,

it's starting to degrade into nicotinamide. Which is not a good thing. No, no. We showed years ago, 2003, that nicotinamide inhibits the sirtuins. It's the negative. So you're doing the exact opposite of what you want to do. Right, right.

So I don't believe in taking high doses of nicotinamide. Some people do. I'm not sure why. Vitamin B3. But nicotinic acid is okay. And if you have NMN or NR, the NR is a version of NMN, I would keep it in the freezer for long term and in the fridge for shorter term. So that'll help preserve it if you end up going down that road.

Right. Looking forward, you know, we've identified these two substances, their relationship with sirtuins and NAD and that potential effect on the body. And you're doing some really exciting research now, which is going to start to potentially show, can we demonstrate the more granular manifestations of what you showed in mouses in human beings? Are there other molecules or substances that you're exploring right now

that you're really excited about? Yeah, there is. So metformin had a big effect on my body. Now, I come from Ashkenazi Jew ancestry. So men in my family typically die from heart disease in their 60s and 70s. And as I mentioned, my father is now a vigorous 80-year-old with no ailments and super strong. Metformin, I think, is part of the reason that we're doing fine. You've got to keep your blood sugar in check. And metformin is one way of doing that. If you get type 2 diabetes, the first thing your doctor will put you on is metformin.

It's a slightly chemically modified version of an extract from plants. The goat's rue, or I think it's called hellebore. It's basically a modified plant extract. It's nothing really amazing in terms of foreign synthetic stuff. But what it does is it seems to trick the body into thinking that there's not enough energy around. And so the body makes more mitochondria and we know that's good, but it also improves the ability of the body to take up blood sugar from the bloodstream. That's all good. But here's the thing about metformin, which is a strange situation.

You need to have that asterisk on your printout at your doctor for them to prescribe it. Because, you know, according to the old rules, you don't get a drug until you're sick. Asterisk being type 2 diabetes. Right. So they measure what's called HbA1c, which is glycated hemoglobin, glycosylated hemoglobin. And that depends on how much blood sugar you've had for the last month or so. But why wait till you've become diabetic

to get a medicine that's very cheap and relatively safe? It's on the list of World Health Organization's essential medicines for humanity. It's very rare that anyone ever has any serious adverse events. There's one in 10,000 or something. It also seems to, by looking at tens of thousands of patients, protect those patients against cancer, heart disease, frailty, and Alzheimer's. This is as close as proof that we've got that a molecule

can slow down aging and diseases of aging. Yet, if you go to your doctor, they're going to say, if you don't have type 2 diabetes, you can't have your metformin. Come back when you've got diabetes, which is the wrong way of thinking about it. So it also sounds like it has a lot of similar effects as the two other substances we talked about. Is that through, but through a different mechanism? Yeah, so there are three main pillars of longevity mechanisms. I've talked about the sirtuins, which there are seven of. There's two others.

One is called AMP kinase, or AMPK, which metformin will stimulate. And then the third one is called mTOR, which is stimulated by low amounts of protein. And that's why people think a plant-based diet might be healthy in part, besides the molecules you get from them. Curious too, I mean, as we start to come full circle a bit, I want to jump back into the nutrition side of things. Like we talked about these things, which are really interesting substances to follow, potentially explore. I want to also be careful when we talk about things like this, and we have a large number of people listening in right now who all have their own unique health situations, lifestyle circumstances. And they're thinking, wow, this is fascinating. This is amazing. Maybe it's right for me. I'm always hesitant. I think you always talk to a qualified healthcare

provider. And at the same time, part of what you're saying is a lot of qualified healthcare providers aren't actually familiar with a lot of what we're talking about. So how do people do that dance of wanting to be safe, wanting to be intelligent, wanting to work with somebody who knows their health, knows their history and can help guide their journey and at the same time be educated and explore sort of like the next generation of what may be coming. Well, I'm glad you said that because I'm not advocating

to just take your health into your own hands. It has to be done with monitoring and with a healthcare professional who knows your body. And everyone's different. So what I'm saying works for me. You might have a terrible reaction to more NAD, for example. Who knows, you might have a tumor that is benefited by what I'm saying

in a growth of a tumor. So you have to be very careful. Now, I also have to be careful that I'm not recommending anything. But what I'm doing is trying to educate the public about what the cutting edge of science is saying. And in my book, actually, everything is referenced. So you can look up the data or show that data to your doctor if your doctor is willing to look at that. But let me just emphasize that we don't know everything, that there is a risk that for that particular person,

especially if they're already taking medicines, they could interfere with medicines. It could be blood thinning. Extra blood thinning is not good, for example. So you want to be able to talk to your doctor, talk about what you're taking. So I'm always honest with my doctor. I tell him that I'm taking resveratrol, I'm taking NMN. What do you think? And he'll, you know, typically he'll say, I need to look that up. But, you know, these are smart people.

They've gone through medical school. They know a lot. And you need to have that conversation with them in case there's something that is particular to you that could be dangerous. Yeah. So as we sit here in this container of the Good Life Project coming full circle, if I offer out the phrase to live a good life, what comes up? The way I look at life is this. I imagine my funeral, actually maybe a little bit before my funeral, on my deathbed. What would make me happy? That's really what I work towards.

It's how I lived a good life. I'm always testing myself every day. So what I'm trying to do is to maximize my contribution. It's almost to be relevant. This is a good life. So how can you do that? Well, you can do it the way I'm doing, which is trying to improve human knowledge and health. But not everyone can be a scientist. So I would say that if you boil it down, everyone should want to leave the world a better place. So how do you do that? Besides being a scientist, you can have children who you take care of, leave them to take care of the world. You can make people happier. You can go to nursing homes and help those people.

As long as you've helped people or even helped animals or helped the environment, as long as you've done something good in your life, an adult hasn't just been about being selfish. I think that's what a good life is about. Thank you. Hey, before you leave, if you love this episode, say that you'll also love the conversation we had with Aviva Ram about how hormones control health in ways that we never imagined and what we can do about it. You'll find a link to Aviva's episode in the show notes. And of course, if you haven't already done so, please go ahead and follow Good Life Project in your favorite listening app. And if you found this conversation interesting or inspiring or valuable, and chances are you did since you're still listening here, would you do me a personal

favor, a seven second favor and share it maybe on social or by text or by email, even just with one person, just copy the link from the app you're using and tell those, you know, those you love, those you want to help navigate this thing called life a little better so we can all do it better together with more ease and more joy. Tell them to listen. Then even invite them to talk about what you've both discovered because when podcasts become conversations and conversations become action, that's how we all come alive together. Until next time, I'm Jonathan Fields, signing off for Good Life Project. The Apple Watch Series 10 is here. It has the biggest display ever.

It's also the thinnest Apple Watch ever, making it even more comfortable on your wrist, whether you're running, swimming, or sleeping. And it's the fastest-charging Apple Watch, getting you 8 hours of charge in just 15 minutes. The Apple Watch Series X. Available for the first time in glossy jet black aluminum. Compared to previous generations, iPhone XS or later required. Charge time and actual results will vary. Mayday, mayday. We've been compromised.

The pilot's a hitman. I knew you were gonna be fun. January 24th. Tell me how to fly this thing. Mark Wahlberg. You know what the difference between me and you is? You're gonna die. Don't shoot him, we need him!

Y'all need a pilot? Flight Risk.