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

21:34Dr. David Sinclair: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, it's just another way of saying we're bringing down aging.

22:20Dr. David Sinclair:We must be, exactly. And we can also now measure that with the biological clock, the so-called Horvath clock, named after 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 it's the exercise you're going to do it's what you love doing uh and it can be a sport uh it could be um windsurfing it could be sailing but just move that's the main thing there's even there's even sex which is we we actually look this up We were really hopeful when we looked this up, but it burns like four calories a minute or something.

23:06It's not as good as...

23:07Dr. David Sinclair: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, and we also looked up the average length of sex, and it's about five minutes. Right. So you're going 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, the Mayo Clinic, recommend at least 75 minutes of vigorous exercise a week.

23:56So that's 15 minutes a day, 10 minutes.

23:59Dr. David Sinclair:And it's better if you spread it out over the week. Right, yeah, 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's usually around mid-40s.

24:35Dr. David Sinclair:That's a good indication of how well you're doing. And if you've got a high heart rate, you're either too stressed or you're unfit, 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, these fitness apps. 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.

25:09Dr. David Sinclair:We're grateful to you, our community, who supports us in this effort. And 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 behaviours 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 show that both too little and too much sleep are both associated with increased cardiovascular and mortality risk.

25:55Dr. David Sinclair:So this brings me to a wearable that I'm particularly fond of, mostly because of its scientific foundation, both here at Harvard, where I work, but also the founder's own research and scientific rigor. They're 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, 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, is wearable to health and fitness coach that gives me insights into my sleep and my recovery, and also my body's strain.

26:33Dr. David Sinclair: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'm 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 of my age.

27:15Dr. David Sinclair: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 Whoop, 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 Whoop band and one month off membership by going to join.whoop.com slash Lifespan or using the code Lifespan.

27:54Let's put a wrap on exercise, but let's have a few takeaways here. And there's really, there's three big ones. Um, the first is a low level of exercise and, and this is just steps, right?

28:10Dr. David Sinclair: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 four, four, four, four is great. Okay. All right. And, um, 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 HIIT, high intensity interval training, or running on a treadmill. That will get your blood vessels flowing and your mitochondria amplifying.

28:4410 to 15 minutes a day. Yeah. That's 75 minutes a week.

28:49Dr. David Sinclair:Yeah, that's what all the experts recommend. Okay. All right. And then muscle building. Yeah. Weights. 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 arms so you look good. But it's pretty simple. You don't need a gym in your bedroom like I do. You can do push-ups, sit-ups, or just have some weights lying around. That's sufficient. All of this is aimed toward the goal of longevity through alerting your genes, your cells, to a state of adversity. Yeah, the adversity memetics. Exercise is one way to challenge the body, but it's not the only way.

29:26Dr. David Sinclair: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 yeah joe said let's go do that after the show which i did um it was pretty chilly i had to strip down into my down to my underwear and put gloves on and socks and whatever but um you get to play music at least uh i got to choose help by the beatles which was is 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?

30:03Dr. David Sinclair: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 shaking. 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.

30:39So what you want to do is middle age, do these treatments 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.

30:51Dr. David Sinclair: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 akin to a vigorous exercise but you still have to have that low level of perceived adversity just like we have to get like 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.

31:23And our bodies recognize that.

31:25Dr. David Sinclair: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 uncoupling proteins and build brown fat. The opposite side of this is heat. Right, taking your body out of its comfort zone.

31:55Dr. David Sinclair:And so the - All of these things are about taking your body out of its comfort zone, right? Yeah. They are, and some of them are really enjoyable. I think sauna bathing, as it's called in Europe, is 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.

32:29Dr. David Sinclair: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 fat. 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.

33:09Dr. David Sinclair: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.

33:49Dr. David Sinclair:and that way, I think you get the maximum benefit from these adversity memetics. 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 homes. Some people have them in their gyms. That's kind of a point of privilege. Most people have a bath or a shower. Or a hot shower. I certainly do that. I like to turn the heat way up. There are a variety of different saunas. 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 saunas and the infrared light actually penetrates the skin and is thought.

34:22Dr. David Sinclair:And there's some evidence, a real believable evidence that also in the skin layer can reverse aspects of aging as well and including improve 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.

35:07Dr. David Sinclair: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 your house you can turn down the temperature or you can use your shower and that will work almost as well as as dunking yourself into a cold bathtub or you could do what gabby reese and led hamilton do which is uh shove us into an ice bath with literally with ice in it i think that you know you don't need to do that every day didn't you almost drown uh i did but that was that was That was hyper hypoxia. What they do is they make you do exercise with weights at the bottom of a pool below your height.

35:46Dr. David Sinclair: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. I think that - That's a challenge. There's not a lot of these centers around and it's expensive. if 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.

36:18Dr. David Sinclair: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 resveratrol, you also started taking resveratrol. how did you know how much to take though? Because you were giving resveratrol 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. You were 3 ,000 times bigger than a mouse. Right, right. It's not just proportional.

36:56Dr. David Sinclair:It's actually more related to our surface area and how much the drug can get into our bodies versus the mouse. And the calculation for a mouse, which is called the allometric scaling, is about 12. So you multiply it. Let's say if the mouse has 100 milligrams 1.2 grams for a human. For a rat, it's three. For a mini pig, it's one to one. Turns out we have about the same surface areas as a mini pig. And so you take about a gram of resveratrol 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. You gotta 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.

37:35Dr. David Sinclair:But I could mix it with olive oil. olive oil recently, as we mentioned earlier, seems to be really good for activating sirtuins, but also you can dissolve resveratrol in it. You get a twofer. 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 resveratrol, you're taking about a gram a day in the morning. Also in the morning, you take NMN. I do. And there 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.

38:07Dr. David Sinclair: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 a 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. Both the past studies and the current studies. Yeah, I take one gram of NMN every morning along with my resveratrol. 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.

38:40Dr. David Sinclair: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 SIRT1 activity should happen. And we actually know this, that the SIRT1 NAD cycle is part of our body's natural 24-hour clock. SIRT1 regulates a protein called BMAL that controls the genes that tell us whether it's night or day, should we be hungry or not, whether we have jet lag or not. And I do find anecdotally that NMN is remarkably good at preventing jet lag as well.

39:14Dr. David Sinclair:I can reset my body's clock sensibly through this SIRT1 B-mail pathway. You're also taking metformin? 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 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 biochemistry.

39:50Dr. David Sinclair: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 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 spermidine. There is. You can buy it now.

40:27Okay, so that's not something you've adopted and you're like, I'm definitely sticking 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?

40:39Dr. David Sinclair:A gram as well. Okay. You are also periodically taking fisetin, quercetin aimed at senescent cells. There are clinical trials being run out of the Mayo Clinic for fisetin and for quercetin. These are high doses. They're typically two grams taken one day a week for a matter of months. 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, yeah. Fisodin and quercetin. Half a gram in the yogurt. Spermidine. Definitely spermidine, yeah, in the morning, about a gram.

41:20And then in the evenings, if you're not working out the next day, metformin how much? 800 milligrams.

41:26Dr. David Sinclair: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. It's 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.

42:05Dr. David Sinclair:And there are ways to do that naturally. So for 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's 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.

42:43But that 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.

42:53Dr. David Sinclair: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. The largest 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.

43:34When we were talking before, I likened this to going to the grocery store and looking at a piece of fruit. Right.

43:39Dr. David Sinclair: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'll talk about ways to do that with our own bodies to really have a quick test and even some molecular tests to determine 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 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.

44:16Dr. David Sinclair: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. Getting 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.

44:55Dr. David Sinclair: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. And you can do this for muscle as well. and I've actually watched my muscle grow as I've changed my exercises.

45:36Dr. David Sinclair: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 GLP-1 drug, If you do take one, a Withings 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.

46:19Dr. David Sinclair: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 slash 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 should, if you're young, pop straight down in less than two seconds. someone in their 30s and 40s, it'll pop straight down. Once you get into your 50s, it's going to take many seconds.

46:58And the chart that you found, and I don't know what the scientific basis for this is, but the chart that you found said, like when you get into your like 80s and 90s, it can take, what, like 20, 30 seconds, something like that?

47:11Dr. David Sinclair:Oh, even worse. So for people like us, we're 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. Looks like yours is - We also sped up the video. Yeah, well, it also helps if you tense your hands. Yeah, and I am definitely, like we don't probably even need to say this, but like it's just obvious. Like I am aging faster than you are aging, but I'm still, I'm doing okay on the skin pop-up test.

47:50Dr. David Sinclair: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.

48:27Dr. David Sinclair: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.

49:04Dr. David Sinclair: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 and reverse aging. And there's a lot to talk about the future of all of this development and what we're going to be seeing in the next five to ten 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. Rarely, but yeah. Once in a while, this isn't just about looking good.

49:39Dr. David Sinclair: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. It was led by Tommaso Bollorini. 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.

50:18If some of these words are sounding familiar, it's because they're all associated with Alzheimer's disease.

50:22Dr. David Sinclair:And there was a second study that I found fascinating. This one was by Anastasio et al, 2017. And it was over a thousand, actually close to 2000 people. And there was a 10 % reduction in dementia risk for people on the Mediterranean diet. 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 really like the Mediterranean diet for 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?

51:06Well, 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 chemically that can help the brain?

51:13Dr. David Sinclair:Well, there are a number of things. I would put them into a few different buckets. 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 SIRT1. 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 SIRT1 is olive oil.

51:47Dr. David Sinclair:And Doug Mastinek recently showed that if you add oleic acid, which is a major component of olive oil, tosylophan 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 what 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 xenohromatic molecules. Plants make these molecules to survive stress. And when we eat them, we get the benefits of that stress because we worry, our bodies worry that our food supply might run out.

52:21And 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.

52:40Dr. David Sinclair: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 are 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, 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.

53:18And these diets 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.

53:28Dr. David Sinclair: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 sirtuins. 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 the ones that make sure you have the methyls that are added and subtracted from the DNA that 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.

54:13Dr. David Sinclair:And there are a lot of studies that have shown that deficiencies in B12 accelerate 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.

54:47Dr. David Sinclair: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 NAD 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.

55:23Magnesium.

55:24Dr. David Sinclair:That's good for sleep. L-theanine 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 counterintuitive, 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? Well, 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.

55:55Dr. David Sinclair: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 like 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 constantly? 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.

56:31Dr. David Sinclair:CRP is? C-reactive protein. Yeah. And so we've got glucose, C-reactive protein, 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 10 years of data, dude. Like, no, I would love to see your like 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.

57:13Dr. David Sinclair:No, it's not just simple as take two pills and call me in the morning kind of stuff or call me in the next decade. It is hard work. You don't get anything for free. You can't just yet 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, okay? 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.

57:48Dr. David Sinclair:Stress your body out a little bit, give it some hormesis. These are adversity mimetics, so a bit of cold, bit of heat, those kinds 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

58:30Dr. David Sinclair: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 at Lifespan and on X at Join Lifespan. 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.