What To Do For Longevity | Lifespan with Dr. David Sinclair Rewind

Welcome to Lifespan. A show where we discuss the cutting edge science of aging and how to live healthier at any stage of life. I'm David Sinclair, a scientist and professor working on understanding why we age and discovering new ways to slow and even reverse the aging process. On this show, I show an insider's look at the latest from my lab, the field and what's just around the corner. When we launched Lifespan's season 1, it was intended as an eight-episode experiment to explore whether there was demand for understanding the science of aging and how to apply it in everyday life. What happened next surprised me, the show became the number one ranked health and fitness podcast and helped spark a global interest in longevity science. Since then, while I've been running my lab to understand how age reversal works and getting the first age reversal drug into humans, almost every day someone has asked me when his season 2 coming. Now that both those endeavors are on track, I'm bringing Lifespan back for season 2, where kicking things off with two special rewind episodes. This one is about how to live longer and healthier, featuring some of the most important and unexpected insights from season 1. From what to do and what to avoid, for a longer healthier life, to some of the most surprising discoveries about aging and what affects it. Longebidi is driven by daily habits, not complexity, just consistency, and I'm going to guide you through it. Even if you watch season 1, go watch these rewinds I have, it's very relevant to our lives today and will prepare you for season 2. Importantly, every insight meets Lifespan's rigorous scientific standards, meaning the science where revisiting remains as true today as it was at the time of recording. This show is actually part of something much bigger. I'm launching Lifespan, a global community designed to connect you with me and other thought leaders, with evidence based insights and the latest advances in longevity research. I've hired a team of PhDs to produce Lifespan magazine, the most accurate source of information to live better longer that you'll find anywhere. At Lifespan, we will support each other in our journeys and learn what actually works together. Lifespan is also very proud to support medical research and the careers of young scientists. If you'd like to go deeper, go to Lifespan.com to sign up for early access and get bonus show content, Lifespan magazine, exclusive ask me anything sessions with me, a book club and much more to come. This show is for informational purposes only and is not medical advice. Please consult a qualified healthcare provider as individual results may vary. Views expressed on my own and not those of Harvard University or Harvard Medical School. Full disclaimer is in the show notes. The one starting place is wait for it drum roll drum roll for long for longevity. The one starting place is eat less often. Those three words eat less often. This doesn't mean eat fewer calories necessarily. It can and that's good. That's good. But a lot of people struggle to do that to eat fewer calories. Well, it comes naturally. If you're down to one meal a day, which I am now, you shed weight and then you get your 20 year old body back. That's a nice bonus. But then you maintain that weight. You have a large adina, which is what I do to make sure I'm not becoming malnourished. Clearly, we're not talking about malnutrition or starvation here. It's about packing your calories into a shorter period of time. That's because packing your meals into a shorter period almost inevitably means less calories. But it's not that's not really what's happening here. It's not just about less calories. It's about what eating less often does inside of our bodies. We'll get to that. It's not just about the period of eating. It's the period of not eating that's so important for boosting the body's defenses against aging to maximize longevity. We'll talk about how that actually works in a minute. You can still have a large body and fast and get the benefits. In my lab, we've looked at mice that are obese and tricked them into thinking that they're fasted and they live just as long as a skinny mouse. So really, it's about getting your body into this state of defense at any weight. Though I would say that there are certain optimal body weights. It's clear that if you're carrying excess weight, you're going to accelerate your aging clock. What we don't want people to do is get the idea though that, oh, good. This works even if you're overweight. And so I can stay overweight. And then as long as I fast a little, it's going to be fine. That's not what you're saying also. Right. There are certain body weights, waist to height ratios that are optimal for humans is about 0.5. But yeah, losing weight is helpful. Interestingly, as a side effect of eating less often, you will lose weight. I did. I've shed about 15 pounds since the beginning of the pandemic. And I look better. I feel better. And it's a nice side effect. Let's get back to the time restricted feeding. You want to have at least 16 hours of not eating or not eating very much. And then you can have eight hours. So typically that means having a late lunch if you skip breakfast or if you prefer to skip dinner, skip that. Because we remember here is that there's a period of sleep in which you are not eating. And so you're really doing is tacking on hours to the front of that and tacking on hours to the back of that. That's right. So when people say I'm skipping lunch, that's not as helpful. And so what I've done in my life, let's just use music as an example of an average human being. Because I'm pretty lazy and I'm not that driven. What I started out in my life was not to eat breakfast. And that pretty much been doing that since I was a teenager. And that for me works because I'm not really hungry in the morning. I have a cup of tea or a cup of coffee and I still do that a little bit of yogurt to mix my supplements with to dissolve them. But you're not doing the yogurt. And I've actually seen you do this. The amount of yogurt that you put into your little bowl is really minimal. It's basically just to mix up your spoon. Yeah, that's it. So that's not going to be a big deal for the rest of the day. And I try not to eat at all until dinner. And then I have a really enjoyable, large-ish dinner. But it's certain type of food. But that gives my body this long window, more than 20 hours of not having glucose circulating from the external world. Partners of the lifespan show allow us to make it freely available as an educational resource to everyone around the world while also supporting medical research. We only collaborate with partners whose products are grounded in strong science and that I've personally used for many years and who also want to help support young researchers. So on that note, let me tell you about one of our partners, a drink I've used for many years called ketone IQ. We all want to perform at our best. When you're exercising, power is one of the most important elements of performance. It reflects how quickly you can generate force and convert your body's energy into movement. In the short term, when you increase your muscle power and reduce fatigue, you improve performance, of course. 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So you can just go to ketone.com/lifespan or use the code "lifespan". Did you ever make any mistakes in fast, like when it comes to fasting itself, because you've tried different kinds of fast, which one really, really didn't work for you? Well, they were all beneficial. Skipping the breakfast was good. I think what got me into trouble is when I tried to do it without preparation. So I said, "Okay, I'm just going to skip lunch and go to dinner without knowing how to do that or being in the right mindset." And I had to quit multiple times. I spent years trying to do this. I could never get rid of my love handles. And this final time that worked for me worked because I found a trick. And that trick, I'm not going to tell you. Oh, I'll tell you. The trick is that you want to fill your body with fluids. For me, constant coffee, tea, hot water all the way through the day, being hydrated and filled with liquid, takes away any feeling of hunger. Also nuts. If you really are really, you need to eat something. protein is known to take away the feeling of hunger rapidly. - Because what my buddy at Cardiologist John Day tells his patients when he's working with them is like, look, if you got it, you just start with a handful of nuts and just give me 20 minutes after that. You're not gonna be hungry after 20 minutes. - So there's an interesting story about the role of protein and hunger and it was first discovered by a friend of mine, Steven Simpson in Australia, and he was studying locusts. And he found out that what turns a locust into a swarm was a lack of protein. And when they get too low in protein, they go crazy. - Locusts get hungry. - And they start eating each other, it's that bad. - And everything else in their sight. - Yeah, and we even see this in the mice that we have on low protein diets, they get super mad and even attack each other. So you don't want to be too low in anything, you don't want to be hungry. But getting back to what really works for me is I'll keep drinking liquids and if I get really hungry, I'll nibble on some nuts and that for me has worked really well. I've got my 20 year old body back for the first time in my life. And I'm never gonna be hungry. - Anybody who starts this, they're gonna be hungry at first. - Of course. - They're gonna be hungry at first. - It's not easy, I'm not saying that it's gonna be easy, but it's worth it. - And there's an important point to make here because we're not talking about starvation. We're talking about intermittent fasting with adequate nutrition. That adequate part's really important. - Yeah, so the acronym would be like that. All right, trademarked that one. I fan, let's call it the new type of dieting. It's important that we add the AN at the end because when we need the adequate nutrition, glucose, particularly fructose is also pernicious. And if you give animals lots of glucose and especially fructose, they will get fatty liver disease, they'll get diabetes. It's really bad. - And this one is like absolutely not controversial, right? Like we're gonna talk about meat later and people are gonna be like really up in arms. But if you say like the big killer of sugar, there's not like a group of people that's gonna come hunt us down. - Like sugar is bad. - It is. - And why? - Well why? Well, there are two reasons that glucose is bad when it spikes three if you include the brain fog, but let's just talk about physiology here. One is that you're gonna have glucose attached to proteins that makes them glom up. Think of it like caramelized body parts. This will ultimately lower your longevity, reduce your longevity, give you type to diabetes and probably cardiovascular disease on top of that. So that's one, keep those glucose levels down, but also what glucose is gonna be doing to you at high levels is shutting off those protective mechanisms. Remember, particularly AMPK and the Sertunes, they get switched off by sugar. So by having that up for most of the day, if you're eating three meals plus snacks, your defenses against disease and aging are gonna be working at a minimum. - So it's sort of like the first step sugars. Let's get rid of the sugars. - Yeah, on that note, by the way, I gave up dessert at age 40, though occasionally I steal it and it doesn't count if you steal it, right? - No, I think there's like a special little pocket that goes into the, it doesn't count against disease. - It's in the, right. - Here's the point. You can quit something, but you don't have to be draconian about it. I still like to steal a, you know, a few scoops of ice cream if I see it, but I'm not gonna eat a giant bowl of ice cream every night. That's, you know, a quick way to short a lifespan. - When I try to ruin everybody's joy. - No, not at all. Often when I give talks at dinner as people skip dessert after I've spoken, I feel bad about that. - Well, you remember we were talking about doing an experiment where we would have a conversation around the table with people and then have the servers come with like a birthday cake or something. You just like watch them. - We still should do that. But yeah, so glucose is a bad one. Something else to avoid is super high protein because mTOR, it can be activated, but you don't want it activated all the time because it's not gonna turn on the autophagy that defences to recycle proteins. - And this one is gonna piss a lot of people off. - Well, yeah, I mean, there's a lot of people who believe that kind of our diets are the best for longevity. - And for some people, a lot of amino's are appropriate. - Well, certainly if you're an athlete or you want to bulk up, there are short term gains. You'll obviously have the protein to build up that muscle, but we can go through the evidence. When you look at populations of what they eat and how long they live, as well as the short term effects when you eat a high protein carnivorous red meat, they stay at, those changes will be good in the short run. But long term, there's no evidence. In fact, I would say there's counter evidence to that being beneficial for longevity if that's your goal. The certain ones also get switched off by high protein as well. - So, amino's are important. We have to have them, if we don't have them, we die. But you can get amino's from plants as well as from animals. - Yeah, it's funny when I say I've gone vegetarian recently, which is a fact. - Oh, are you gonna get your protein? - Yeah, where do you get protein from? Well, what do you think plants made of? It's also mostly protein. Now, they're not as bioavailable, so you're getting like two thirds of the amount as you would from a state. - You might have to work a little harder for it. - Great. I want my body to work harder. It's good for it. It's also activating these defenses, as we mentioned. So, I'm now trying out this full vegetarian diet. I'm not yet vegan, but that actually probably works even better for longevity as the science will tell. - How's it working for you? - You feeling? - Do you miss me? - I do. I love meat. I think meat tastes great. But I'm more and more inclined to enjoy visual as well. - Let's bring this all together now. Eat less often. - Yeah. - And don't snack. - And don't snack. - Avoid sugary drinks and foods. - Eat less often when you do eat, kill the sugar. - Yeah. - I focus on, I try to eat naturally occurring sweeteners. - Okay. - Start working toward reducing your meat intake. If you're dieting, if you're diet is aimed at longevity, very likely you're gonna need to drop your meat intake. - Yeah. - It causes a lot of concern of people who are pro meat, but the data is the data. Reducing the amount of red meat and in particular, processed meats is beneficial for long-term health and even prevention of cancer. One of the things that's not appreciated about red meat, there's a molecule called TMA that is in the meat that goes into the bloodstream. The liver turns it into a toxic molecule called TMAO. And this TMAO is shown, at least in animals, to enhance, accelerate cardiovascular disease. And so what we wanna do is to limit the preserved meats. If you like a good steak, by all means eat one. It's not gonna kill you, but if you try to just push yourselves towards a more plant-based, plant-focused diet and maybe have some olive oil with a lair acid which activates or tunes as well, the Mediterranean diet is the one that I think is likely to be the easiest to do in the Western world and to have the biggest bang for the buck. You can go a little bit further, like I have, don't eat meat and eventually maybe I'll give up everything that's dairy and eggs. But the Mediterranean diet is a very enjoyable diet. I lived on it for over a decade. And one of the things that's not well known is that there are studies of Mediterranean diet versus Western diet. And it's a massive difference. There's one here that was published in just 2000. There was a reduction in mortality. - In 2000 or in 2000, the year 2000. - That's why-- - 20 something years ago. - 20 something years ago, but there are a lot of studies since, there's at least five studies that have backed this up. If you switch to a Mediterranean diet, if you're under 80 and you do that, you reduce your mortality chances of death on any given day by 31%. - I look at like if you're under 80, which means you can still take advantage of this, even if you're way deep into your life. - Right, and I would say probably in this study, they just didn't include it, people are over 80. So I don't know for a fact that it wouldn't work on 80-year-olds. - It's sure, right. - But yeah, that's the point that's really important. When, often when I give talks to crowds, they are elderly. And often the question comes up, is it too late for me? The answer is it's never too late. Dietary changes in older people can have massive benefits. Some people say, oh, you need to have a carry-bit of fat on people that, if you're over 80, you should have a little bit of body fat. - There was a study that a lot of people latched on to that they're really excited about because it's like, oh, if you're older, you can be fat. - Yeah, well, it turns out that's not true. When those studies have been redone, being lean as an older person is also beneficial. If you go to a nursing home, I don't know how many people listening have been to a nursing home, but when you go there, look around, who's alive? They're not giant men who are obese. They're little women who are skinny. There's an experiment right there. It's obvious, right in plain sight. - Okay, so, eat less. Start working toward fasting, cut the sugar, cut the meat, eat the veggies. And if you are gonna eat the veggies and you can find ones that have been stressed out and are enjoying a little Xenohormatic, you may enjoy a little Xenohormatic effect from that. - That's great. And there's even an order which you can eat your meals to reduce the blood sugar spike. You can put the sugar at the end of the meal. So dessert is fine, but put it at the end. Don't start with sugar. Don't start with the carbohydrate because that will immediately spike your glucose. - So if you are gonna go back to that like the second or third point, If you are going to eat sugar, eat it at the end of the meal. Right. What you eat during the meal in which order also makes a difference. And not with the protein and the fat. And if you're in the day, that's just. Oh my goodness. Eating candy during the days is just going to make you feel lethargic when that sugar goes away. Nutrition is foundational, but it's only one side of the longevity equation. The other is movement. And as we'll see, simply getting your body out of a sedentary state can have profound effects on aging. But the point here is that sitting down is bad for us. You atrophy, you have less muscle, and you become, you know, in pain. That's not a good thing. But ultimately, if you have not a lot of muscle in your hips, particularly, you can break your bones when you fall over, when you're older. And all of that means you need to get off your butt, stand up, even better, go for a walk, even better, go for a run or cycle to get what we call a hypoxic state going. Your body needs to suck in my oxygen. And that has remarkable health benefits. We actually have to actively pursue opportunities to do this, to get this, to get exercise to promote this adversity, memetic effect, because our lives are built around comfort and sedentary nists. Yes, that's true. And what I think most people don't appreciate is that exercise isn't just beneficial for your fitness and for your vitality. It actually can stop diseases in the attracts. These can slow down cancer. In fact, it can prevent up to 23% of all cancers from occurring. That's true for cardiovascular disease. In fact, it has an even bigger effect on that. 30% reduction, just by doing moderate exercise every week. 50 minutes is sufficient or three times a week with 10 minutes. I love this idea of connecting the idea of all-cost mortality with aging, because as we've presented here, as you've been arguing for quite some time, most diseases, which bring us toward the end of our lives, are really just an accumulation of the symptoms of aging. And so if you bring down the disease rate across various diseases, which is bringing down all-cause mortality, you're really just, it's just another way of saying we're bringing down aging. We must be. And we can also now measure that with the biological clock, the so-called Horvath clock, named off to my good friend Steve Horvath. That is now a measure of the process that leads to all of these diseases that kill us. And one way that we know for a fact to slow down the ticking of that biological clock is exercise. What's the best kind of exercise? Well, there isn't one exercise you're going to do. It's what you love doing. And it can be a sport, it could be wind surfing, it could be sailing, but just move. That's the main thing. There's even sex, which is, we actually look this up. We did look this up, we were really hopeful when we looked this up, but it burns like floor calories a minute or something. It's not as good as. Well, I'm sure it depends on the individual, right? I mean, you can make sex more aerobic. You can make it part of your exercise regimen, but you have to have a partner, a consenting willing partner who also wants to make it part of their exercise regimen. It's only 4.2 calories per minute, which. And we also looked up the average length of sex and it's about five minutes. Right, so you've got to burn 20 calories if you're an average person. I'll burn 10. So instead of that, you probably need to go for a longer walk afterwards to really burn off those calories and get your blood flowing. And however you get your exercise, be it running or sailing apparently or sex, both the World Health Organization and the Mayo Clinic recommend at least 75 minutes of vigorous exercise a week. So that's 15 minutes a day. 10 minutes. And it's better if you spread it out over the week. Right, yeah, you don't do it all at once, but that's the starting point. And most people can do that. You can be the busiest person in the world. You can be the most unhealthy person in the world. You can get your heart rate and your breathing up for 10 minutes a day. Sure you can. And the benefits will be huge. You'll feel better. You'll look better. And you'll also have a better resting heart rate. That's one of the best measures of your fitness. If you're less than 50 for a resting heart rate, that's really good. For someone my age in my 50s, mine mine's usually around mid 40s. That's a good indication of how well you're doing. If you've got a high heart rate, it's you're either too stressed or you aren't fit, try to bring that down again. You can measure your heart rate pretty easily. Just put your hand on your arm, but you could also either wear a ring or a new fitness or these fitness. And there's all kinds of wearables now that are going to help you do this. Yeah, and I'm a big proponent of measuring things, right? Because otherwise you're flying blind. Here at lifespan, one of our most important missions is to support medical research. So down the line, all of us can lead longer and healthier lives. We're grateful to you, our community, who supports us in this effort. We're also grateful to our partners who help us in this mission. So speaking of which one of the most consistent findings in longevity science is that small and measurable behaviors add up over time. For example, in 2011, a study was published in the Lancet, a very reputable journal, where researchers followed over 400,000 individuals. What they found was that just 15 minutes of moderate exercise per day was associated with a roughly three year increase in life expectancy. Sleep shows a similar pattern. Large-scale analyses published in the Journal of the American Heart Association showed that both two little and too much sleep are both associated with increased cardiovascular and mortality risk. So this brings me to a wearable that I'm particularly fond of, mostly because of its scientific foundation. We're here at Harvard where I work, but also the founders own research and scientific rigor. There are only a couple of blocks away from the studio up the street. And whenever I visit, I see a thriving company that's mission-oriented to help people live better at longer lives, including all of us. And of course, I'm talking about whoop. The whoop band, which is the one that I rarely take off my wrist, this wearable to health and fitness coach that gives me insights into my sleep and my recovery and also my body's strain. So I can see really how my daily behaviors are impacting my health day-to-day. For example, wearing the whoop over the last two months, I've seen dramatic improvements in my personal biomarkers indicating that the changes that I am making to my lifestyle, including a much healthier diet, cutting out a lot of the extra carbs that I was eating. And a bit more exercise, they definitely were having positive effects on my body. And I was talking about this with Andrew in the studio here about my resting heart rate, which has gone down to 45. And my heart rate variability, which you want to be higher, this HRV number has shot up to 90, putting me in the top percent or so for my age. It's not only interesting and useful on a daily basis, but I'm building up a record about my body that I can aim for when I'm older. So when I'm 90, I can go back to being 50 or younger. As I mentioned earlier, lifespan and I only partner with companies like Woop, who we really believe in and these are products we use daily and also who align with our mission of supporting medical research. You, our lifespan community and listeners can get a free Woop band and one month off membership by going to join.woop.com/lifespan or using the code lifespan. Let's put a wrap on exercise, but let's have a few takeaways here. And there's really, there's three big ones. The first is a low level of exercise and this is just steps, right? Get off your butt. Get off your butt and dig. Yeah. Standing desk or a desk with a treadmill walk around the block after dinner or lunch. Those are the simple things. And you don't have to hit 10,000 steps but shoot for four. Four is great. Okay. All right. And then that's the low intensity exercise that everybody should be getting throughout the week every single day. You should also get high intensity exercise. For sure. A few times a week, 10 or 15 minutes, lose your breath. It can be the form of hit, high intensity interval training or running on a treadmill. That will get your blood vessels flowing and your mitochondria amplifying. 10 to 15 minutes a day. Yeah. That's 75 minutes a week. Yeah. That's what all the experts recommend. Okay. All right. And then muscle building. Yeah. Wait. That's just as important. So maintain that muscle mass. Exercise the big muscles, particularly. Don't forget about those. Don't just work on your upper arm so you look good. But it's pretty simple. You don't need to gym in your bedroom like I do. You can do push ups, sit ups. We'll just have some weights lying around. That's sufficient. All of this is aimed toward the goal of longevity through learning your genes, your cells to a state of adversity. Yeah. The adversity mimetics. Exercise is one way to challenge the body, but it's not the only way. There are other forms of controlled stress that can activate these same longevity pathways, including something a bit more extreme, cold. And cold therapy, people call it cryo therapy. You've done this before, right? You did this with Rogan, didn't you? Yeah. Joe said, let's go do that after the show, which I did. It was pretty chilly. I had to strip down into my underwear and put gloves on and socks and whatever. But you get to play music at least. I got to choose help by the Beatles, which was quite appropriate because by the end of those three minutes. You wanted out. Well, the first two minutes, I'm like, what's the problem? This isn't cold, but that last minute, I really thought I was going to get hypothermia and my ears might break off. You're chattering and shivering. Yeah, you really start to shiver, which is your body's way of generating heat by moving your muscles. But it was really enjoyable. I found afterwards, I felt stimulated. I felt lucky to be alive. And I felt good for a number of days afterwards, which is probably because my mitochondria were revved up. The one thing I think it's worth pausing here to talk about is why would you do this now? Why don't you wait till you're old to do cold therapy? And what's been found, at least in mice, is that old mice don't make brown fat as well as young mice. So what you want to do is middle age do these treatments, and so that you're ready for old age when it becomes harder. Just like right now, we need to be doing vigorous exercise. We can't wait until we're old to do vigorous exercise. Yeah, though it's never too late. We do find that things work in elderly mice and elderly people, but it doesn't work as well if you start midlife or even earlier. Okay. And maybe that's like the cryotherapy stuff is sort of a can do vigorous exercise, but you still have to have that low level of perceived adversity, just like we have to get lots and lots of steps in every day. But we live in these environments, these temperature-controlled environments where it's like 68 to 72. That's not how our ancestors lived at all. No, we were shivering probably most of the time during the ice age for sure. And our bodies recognize that. We've got those genes that respond and they keep us healthy. So there are a number of ways you can, if you don't have a cryotherapy center near you, what do you do? Well, you can take cold showers. Some people do that. I don't, I find that unpleasant, but you can do that. It's very cheap to do that. Or you can do something that I do actually do, which is sleep with very few covers on my bed and lower down my body temperature. And that's also been shown to activate these uncoppling proteins and build brown fat. The opposite side of this is heat. Right, taking your body out of its comfort zone. And so all of these things are about taking your body out of its comfort zone. They are. They are. And some of them are really enjoyable. I think sauna bathing is cold in Europe. It's super enjoyable. And it also is good for your skin. You get to sweat and get those pores unclogged. But this is one of the most ancient therapies for longevity. Even before Roman times, they were bathing in these saunas, though the Romans would use fires under the floor. But this is something that Europeans still carry on as a tradition, particularly in Finland and other Scandinavian countries, where these studies are typically performed on men for some reason. But the data that I've looked at is that there's absolutely no doubt that men who partake in sauna bathing a few times a week, often at home, because they build this into their houses, have a dramatic reduction up to 20% in the rate of cardiovascular disease and mortality caused by heart attacks. This isn't happening for the same reason as cold therapy work. This has nothing to do with brown fats. There's another thing that's going on here, right? It's different in this case. What we think goes on in a sauna is you're activating HSPs. And these heat shock proteins are helping to fold proteins correctly and also stimulate pathways that are beneficial, such as building new blood vessels, making more mitochondria. And one of the reasons that I believe it's true is that in model organisms, if you take a worm, if you turn up heat shock proteins, either by giving them a lot of heat or genetically modifying them, they also live longer. Before the pandemic, I used to go at least once a week and do multiple bouts of the heat shock in the sauna for about 15 minutes and then jump in an ice bath, which was nearby for four minutes and then cycle that. You should probably consult your doctor before you do that. I would definitely, and I did. But yeah, it can put some stress on the body, certainly on the heart. But yeah, the idea though is to shock the body, heat cold, heat cold. And that way, I think you get the maximum benefit from these adversity mimetics. And again, you don't necessarily need to have access to a sauna to do this. I mean, some people can build them into their home. Some people have them in their gyms. That's kind of a point of privilege. Most people have a bath. Or shower. Or hot shower. I certainly do that. I like to turn the heat way up. There are a variety of different sonars. There's the old-fashioned type, which is the cedar planks sitting in there. And you just throw water on hot rocks. That's traditional. There are new ones, such as infrared sonars. And the infrared light actually penetrates the skin and is thought, I mean, there's some evidence, a real believable evidence, that they're also in the skin layer can reverse aspects of aging as well. And including improved hair growth. So let's talk about a basic protocol with the caveat that we always make, which is everybody's going to be a little bit different. But if we're trying to get sort of, you know, like exercise, cold heat and hyperbaric, what's a good way to do that? Well, as I mentioned, I used to do, and I will do again, the cycling of the heat and the cold, about five times during one day of the week. This was on a Sunday with my son, Benjamin. But I would say more is better. There's no evidence that you can overdo this. You could even do it every day. If you don't have access to a gym, you can always use your house. You can turn down the temperature, or you can use your shower. And that will work almost as well as dunking yourself into a cold bathtub. Or you could do what Gabby Reese and Lead Hamilton do, which is shove us into an ice bath with literally with ice in it. I think that you don't need to do that every day. It didn't you almost drown? I did, but that was different. That was hyper-hypoxia. What they do is they make you do exercise with weights at the bottom of a pool below your height, so you're underwater, and you have to jump up with those weights to get a breath in there. We're not recommending that at this time. I think everybody should go knock on their front door and do it with them. No, it's, but you can get hypoxia from exercise. It's very similar. So we've talked about hot and cold. The hyperbaric is more of an issue. That's a challenge. There's not a lot of these centers around, and it's expensive. It's hundreds of dollars per treatment. But that's in the future. I think that that, I wanted to mention that because it's really interesting how it's so similar to exercise and hypoxia at the molecular level. But for most people right now, that's out of reach. Beyond lifestyle, there's growing interest in molecules that may amplify these longevity pathways. While this area is still evolving, I'll share what I personally take and the science behind it. When you started investigating risk veritrol, you also started taking risk veritrol. How did you know how much to take though? Because you were giving risk veritrol to yeast and eventually to mice. Well, it's not a one to one. It's not like you should take 3,000 times as much as the mouse had. This is more 3,000 times bigger than a mouse. Right. It's not just proportional. It's actually more related to our surface area and how much the drug can get into our bodies versus the mouse. The calculation for a mouse, which is called the "alometric scaling" is about 12. You multiply it, let's say, if the mouse has 100 milligrams, 1.2 grams for a human. For a rat, it's 3, for a mini pig, it's 1 to 1. It turns out we have about the same surface areas as a mini pig. So you take about a gram of risk veritrol every day? I do, and I've been taking that since about 2004. But like I said, you can't just put it in water and drink it. Add some fat to it. Yeah. So I typically have some yogurt, a couple of spoonfuls, not a lot because I'm trying to fast until dinner. But I could mix it with olive oil. Olive oil recently, as we mentioned earlier, seems to be really good for activating so-toins, but also you can dissolve it as veritrol in it. Do you get a tooper? You do. I don't have a lot of it. There's a lot of calories in olive oil. I don't want to break the fast severely. But mix it with a bit of vinegar and basil leaves and it doesn't taste too bad. Okay. So, risk veritrol you're taking about a gram a day in the morning. Also in the morning, you take NMN. I do. And now you don't have to worry about food. It's dissolved easily. You can put it in water or swallow it, put it under your tongue. And so I do that. That's my main combo in the morning. How much NMN are you taking in the morning? Again, it's gram, but that's not, I guess, that's actually based on the human studies that we've done that show that a gram over 10 days raises your NAD levels about twofold. And that's sort of the dosing amount that we're seeing in a lot of the human studies now. And that's both the past studies and the current studies that we're going. I take one gram of NMN every morning, along with my res veritrol. The reason is in humans we know that that doubles NAD levels, which is important because someone my age has half the levels of NAD than I did when I was 20. But you can go as high as two grams and triple the amount. It's important to mention that I take these at a certain time of day based on science as well. I take these in the morning because that's when the natural rise in NAD and certain one activity should happen. And we actually know this that the certain one NAD cycle is part of our body's natural 24 hour clock. So it one regulates a protein called B-Mail that controls the genes that tell us whether it's night or day, should we be hungry or not, whether we should have, whether we have jet lag or not. And I do find anecdotally that NMN is remarkably good at preventing jet lag as well. I can reset my body's clock sensibly through this sort one B-Mail pathway. You're also taking that form. Yes. How much when? I take 800 milligrams at night. Okay. And you take that at night because? Well, because doctors tell me that it's a good time to simulate a fast. I take it with my dinner just after. And then through the night, I'm presumably having low levels of glucose. And my body has all the benefits of stimulating those repair pathways, those survival genes. And that's the most recent thing that you've added to your regimen? It is. Actually, what happened was I had terrible blood by chemistry. I was eating badly, I gained weight. I wasn't sleeping. I was stressed. And those numbers just went through the roof. And I said, I've got to do something. So I went on NMN and things. were somewhat rectified and then I added Metformin and they really got back to my optimal. We mentioned earlier some concerns about exercise Metformin. Your practices were that concerned? Yeah, I pulse Metformin. It doesn't sit well in my stomach anyway. So on days where I know next day I'm going to exercise and lift weights, I might skip Metformin that night before. And then there's also spermini. There is. You can buy it now. Okay. Sometimes something you've adopted and you're like, I'm definitely taking with it. This is, I'm adopted and I'm testing it out to see how it works. I am. How much of that are you taking? A gram as well. Okay. You are also periodically taking Ficetin, Curestidin, Amd at Ceneous itself. There are clinical trials being run out of the Mayo Clinic for Fizzidin and for Corsidin. These are high doses that typically two grams taken one day a week for a matter of months. I'm myself, I'm on a maintenance dose. I take about half a gram of each every day. Let's take this morning through night just really quickly. Resveratrol, one gram. In the morning with yogurt or olive oil. NMN as well. A gram, yep. Ficetin and Curestidin. Half a gram in the yogurt. Spurminine. Definitely Spurminine, yeah. In the morning about a gram. And then in the evenings, if you're not working out the next day, metformin, how much? 800 milligrams. Okay. That's it. That's it. Now, you're not most people. A lot of other people are going to be different. You don't advise people, but it might be a good place for people to start their conversation with their doctor though, yeah. Well, I think so. Most doctors are open to hearing about the latest science. It's very difficult for them to keep up with it. One of the reasons we're doing this podcast in the first place. Of course, supplements are just one layer. For some, the next step involves medical interventions, but these require a very different level of caution and oversight. People need to have a naturally healthy level of hormones in their bodies. And there are ways to do that, naturally. So if testosterone, you can work out the bigger muscles in your body, and that'll also help with growth hormones. So I work out my thighs and my back, particularly. Keep those nice and strong. And I've found my natural testosterone levels go up to normal levels with that. So that's a way to do it. With growth hormone, it's all about eating at the right time and sleeping. So if you eat not too close to sleep time and then you rest through the night and have a good night sleep, that's the best way to improve your growth hormone levels. And if you're doing all of that and you're still struggling to keep these levels up, that's the time to talk to your doctor about supplementation. But that supplementation needs to be aimed not at hyper-increasing the levels of these in your bodies, but just keeping them at that sort of like that natural, healthy level. Well, exactly. But I would encourage everyone to try it naturally first. Interestingly, many of these internal processes don't just affect how long we live. They influence how we look. And the skin offers a visible window into biological aging. First organ in the human body is the skin and it's sizable. Well, it's one sixth of your total body weight, which is massive and it's the barrier to the world. And the health of your skin is super important for the health of the rest of your body and vice versa. And monitoring the health of your skin can give you a lot of insights into the health of your body. When you're talking before, I likened this to going to the grocery store and looking at a piece of fruit. Right. If you see some bruises and some damage on there, you can assume that it wasn't handled very well, but also it might be old. So you give it a squeeze, you see how it is. And we can, we'll talk about ways to do that with our own bodies, to really have a quick test and even some molecular test that's determined how molecularly old we actually are. If you've listened to this show or heard me on stage, you've probably heard me say, you can't optimize what you don't measure. That's what we do as scientists. It's true also when it comes to body metrics. Many people only measure their total body weight if anything, but this only tells a small part of the story. You don't know if you're losing fat or muscle or even where the fat is being lost from. For instance, visceral fat, what I call the evil fat that sits around your organs, it's associated with increased risk of cardiovascular disease, diabetes and death. And rid of visceral fat or at least minimizing it can have a strong impact on your long-term health and longevity. Since they first came out with their Wi-Fi scale over 13 years ago, I've actually been using withings devices. And if you've never heard of withings, they make some of the coolest devices that you can measure yourself with. The scale is one of the devices that I particularly love. I've got all the valuable data over 13 years on my scale and on my phone, along with those of my kids as they were growing up. Let me show you what my body looks like in 3D, my digital twin. There I am. You can see that on my arms, 11.5% fat, legs, 10.7% and torso, 13%. I'm pretty happy with this. I'd like to be a little bit more cut on my torso, but it's telling me that I'm doing well and I'm on the lower end compared to other people in my age range. You can do this for muscle as well and I've actually watched my muscle grow as I've changed my exercises. This is just one motivational and very fun thing to have on your phone and it's fun to show others as well. In the past couple of months, by changing my diet and my exercise regimens, I've lost over 12 pounds and importantly I was able to ensure that I didn't also lose any of my muscle mass, which is a common problem. And though I didn't use a GILP1 drug, if you do take one, a within scale can help ensure that you lose fat, not muscle. So withings is really cool. It's the only smart scale that comes with an FDA-cleared ECG that can analyze your heart rhythm and even detect atrial fibrillation, a heart condition that can cause stroke and heart failure. As a lifespan listener, we invite you to join us, learn more about withings or get a scale or one of their other cool smart devices at withings.com/lifespan or use the lifespan code for discounts. There's one you've been doing all morning this morning. Do you want to do it now? The skin pinch test. Yeah. Sure. Well, so what you do is you rest your hand on a table so it'd be relaxed normally and then you grab the back of your skin, pinch it up and it's should, if you're young, pop straight down in less than two seconds. When you get into your 50s, it's going to take many seconds. And the chart that you found, and I don't know what the scientific basis for this is, but the chart that you found said, when you get into your 80s and 90s, it can take 20, 30 seconds, something like that. Oh, even worse. So for people like us who are in our 40s and 50s, it should be less than 10 seconds. By the time you're 60, it typically takes 10 to 15 seconds to come down over 70 between half and a whole minute to go down. Okay. And you're 50 and yours went down right away. So that's good. Well, I've been doing the right stuff for a number of years, but that's pretty good for someone my age. It looks like yours is better on the video. It also helps if you tend to have a lot. Yeah. We don't probably even need to say this, but it's just obvious. I am aging faster than you are aging, but I'm still, I'm doing okay on the skin pop up test. You are. You mentioned earlier sun damage, staying out of the sun is really important. Smoking is really bad for your skin. That's probably the fastest way to accelerate aging in your body. And it shows up on your skin. There's no question you can even see the difference in people. A lot of people don't know this, but alcohol also shown in research to be pretty bad for our skin. So if you don't need. Right. I didn't know that. I only recently gave up alcohol and having seen that study. And sort of like along those same lines, smoking alcohol, bad food, eating processed foods, eating foods that are like rich in fats and chemicals and all that gross stuff. Yeah, it's amazing how much your food can affect the aging of your body and your skin. And you can see the big difference. If you've ever had a pet and you change the diet of the dog, for example, we see this in our mice, we feed them good food and their skin and their hair changes radically. And that's the important transition point there. The hair also changes as well. What's good for your skin generally is good for your hair too. So we've covered a lot today. The big takeaway is that we're on the verge of being able to reverse aging in the body internally, but also externally. And that'll be a world where people not just live longer, but feel better about themselves as well. We've talked about injectables, edibles, smearables. It's a lot of ways of getting these molecules into the body, not just ingesting them, but putting them on the surface and getting them into the layers where they needed to slow down or reverse aging. And there's a lot to talk about about the future of all of this development and what we're going to be seeing in the next five to 10 years as well, which we'll cover in a later episode. You thought it was a superficial topic? I did. I thought it was a superficial topic and I can admit when I'm wrong. Really? But yeah. And for a while, this isn't just about looking good. So the moral of this episode is if you can keep yourself looking good by doing the right things, you'll probably end up living longer too. We've talked previously about the Mediterranean diet. And one of the reasons is that it's very clear in over a dozen studies that a Mediterranean type diet protects the brain from aging and can even reverse aspects of aging. in the elderly with mild cognitive impairments. - Yeah, there's a study from a really large international research group that was led by a tomasso ballerini. It showed higher adherence to a healthy diet. In this case, the Mediterranean diet is associated with less amyloid beta, less tau, larger gray matter, volume. If some of these words are sounding familiar, it's because they're all associated with Alzheimer's disease. - And there was a second study that I found fascinating. This one was by Anastasia at L, 2017. And it was over a thousand, actually, close to 2,000 people. And there was a 10% reduction in dementia risk for people on the Mediterranean diet. And the-- - There's actually a 10% risk reduction for each Mediterranean diet score, which means the more Mediterranean your diet, the better you were doing. - Right. And so that includes olive oil in the diet and not a lot of red meat. - Yeah. And not surprisingly, this is a research team from Greece. They're really like the Mediterranean diet. - And they're probably the most obvious reasons. - Yeah, what I want to get into later, and hopefully we will, is what is it in that diet? Chemically, that can help the brain. - Well, I don't know that we need to wait too long to get into that. Let's talk about that. Like, what is it in that diet? - Well, there are a number of things. I would put them into a few different buckets. That there are vitamins that can be deficient. That we need to talk about about the clock later. Polyphenols, resveratrol is one of those. And my lab has been working on resveratrol for many years. And that directly activates certain one. It makes the enzyme, it's like a Pac-Man, and it's controlling genes, and it works faster. So resveratrol has clearly been shown to be beneficial, and also prevents cancer, and not just has metabolic and brain enhancing effects. The other component of Mediterranean diet that works on certain one is olive oil. And Doug Massenak recently showed that if you add oleic acid, which is a major component of olive oil, to soften and avocados, and other good foods like that, can also directly activate the enzyme by sticking to it and making this Pac-Man, I don't know if everyone knows that a Pac-Man is this little puppet creature on an electronic game, chomp faster. And there's probably other molecules. We talked previously in another episode about Xenoharametic molecules, plants make these molecules to survive stress, and when we eat them, we get the benefits of that stress, because our bodies worry that our food supply might run out. - And that's sort of the overarching nature of a plant-based diet, whether it's Mediterranean diet or some other diet, is that it is mimicking adversity. Your body's got to work a little harder to get everything that it needs, that's sending the signals that maybe times aren't so great, and we need to activate these longevity pathways. - Well, that's the difference between a Mediterranean diet and a high fat carnivorous diet and a typical Western diet. They're full with calories, full with a whole bunch of stuff that tells the body times a good. It's a bounty, no need to protect ourselves. Let's just burn the candle at both ends and forget about life later. And that's not what you want. What you want to do is to have the perception of adversity and the Mediterranean diet, as well as in Japan, that what's called the Okinawan diet, which has low levels of protein and mostly plant-based. Those two trick the body into thinking that the food supply sucks and could run out any minute. - And these sides aren't perfect, right? Let's talk about some of the things that you need to make sure that you're getting enough of if you are eating this plant-based diet. - Right, well, one of the first things to worry about if you're just focusing on plants only is a deficiency in vitamin B12. There are other B vitamins that are also important to make sure that you have enough of vitamin B6 and B3. We've talked about B3 as an early component that's building up that NAD for the sort of two ends. So B vitamins, especially if you're on a plant-based diet, but for everybody, don't be deficient in these. Why? Because the B vitamins are one, other ones, that make sure you have the metals that are added and subtracted from the DNA, the controls, the DNA methylation clock. If you have low levels of B12, it's known that you have deficiency in the ability to methylate DNA and that will mess up your epigenome and very likely accelerate the clock in a way that causes aging. And there are a lot of studies that are showing that deficiency is in B12, accelerate of a variety of diseases, heart disease is the major one, but also dementia in the brain. And the main reason I think what's going on is that aging is being accelerated when you don't have enough of these B vitamins. And if there's one factor that ties all of this together, nutrition, exercise, brain health, it's sleep. Because without it, many of these longevity pathways simply don't function as they should. As you get older, you lose your ability to sleep and if you don't sleep well, you'll lose your ability to fight aging and it's just a feed-forward disaster. So you've got to intervene. You can intervene with the kind of things we talk about here, which is eating well, exercising, and intervening with the kind of things that you can take, perhaps as a supplement. But now let's talk about what do we do to make sure we sleep well and we have the right rhythm. And one of the key things that I use is NMN. NMN is going to raise any D levels in the morning. I take a gram of it then. But I also, when I travel, I use it to reset my body. And I definitely feel that I can avoid jet lag if I do that. There's some other supplements that a lot of people take. Magnesium. That's good for sleep. Elfthienine is another one that people try. I've used it. It seems to help me. But essentially, you just want to calm down at night. Don't do your emails too late. Relax your brain. And then I think a little counter-intuitive. One of the best things that you can do for sleep at night is actually not something you do before you go to sleep. It's something you do right away when you wake up. You mean go outside. You've got to get light, right? You've got to reset your circadian rhythms and the best way to do that is put yourself in a situation where your body knows it's daytime. Try to get some light early in the morning because that always gives you an energy boost and helps you reset your circadian rhythms if they're not perfectly in sync. What are the five biomarkers that you would want to have? If I just said you can only have five this week, what are the five that you would want? Well, I'm already measuring a lot of those. What would you want to be able to monitor glossantly? So I would want one of these devices to not just tell me glucose. I want it to include heart function, which I'm doing as well. But I also would include inflammation. So there's a molecule called CRP, which I always want to keep low because that's a really good predictor of cardiovascular disease. CRP is. C-reactive protein. And so we've got glucose-reactive protein, inflat inflammation. So this would be TNF alpha or IL-16. These are also predictive of longevity. I want cortisol, keep my stress levels down, or also telling me if I overexercise. I would love to see your cortisol chart. I have it all. I've got TNFs of data, dude. No, I would love to see your minute-by-minute cortisol chart. Well, yeah. Hanging out with you raises it for sure. If somebody wants to partake in this future and they're of any age right now, they actually have to put in the work. It's not just going to be handed to them in the next few years. No, it's not just simple as take two pills and call me in the morning kind of stuff, call me in the next decade. It is hard work. You don't get anything for free. You can't just get pop a pill and go back 20, 30 years, though maybe in the future we will. But for now, the best recipe for long life, greater health, and ensure that you make it past 80, 90, maybe even into your hundreds is to do the right things. There's eat the right way. Eat the right kind of diets. Don't eat as often, have some period of fasting. Get some type of exercise, even better, do multiple different types of exercise. Stress your body out a little bit. Give it some hormesis. These are adversity, mimetic. So a bit of coal, a bit of heat, those kind of things. The other thing we talked about is some supplements. And these new technologies we've talked about today, the monitoring and other things, that will actually allow us to live longer. And you might say, well, do I care about living longer? Well, absolutely you should. Why? Because the longer you live, the longer you will live. Right now, if we live an extra year, we get another three months of life, because these technologies are going so fast. And soon, we'll have another six months of life every year we live. And eventually, another year for every year we live. And that's when things get super interesting. To learn more and join our community, visit lifespan.com, where you can get early access to future episodes, the lifespan magazine, and detailed show notes, transcripts, and links to the papers we've talked about today. If you found this episode valuable, do hit the subscribe button, wherever you're listening from today. And for the latest discoveries on a daily basis in longevity science, follow us on Instagram @lifespan and on x @joinlifespan. From all of us at lifespan, thank you for being part of this growing community. And remember, life is short. Let's change that together.