What to Eat & When to Eat for Longevity | Episode 2

I'm David Sinclair. I'm a professor at Harvard Medical School who researches the biology of aging. And I'm co-director of the Center for the Biology of Aging. And I'm joined by my co-host and co-author Matthew Lepland. Hey. We're back. Hey. Welcome. Good to see you again. Good to see you again, too. This is episode two. We're going to be covering when to eat and also what to eat within 24-hour periods as well as over a year. Not just to maximize your wellness and how you feel and look, but how to maximize your overall longevity. I'm going to talk about some of my protocols as well that I've developed over the last 20 years, being a researcher in this area, and what works for me and what might work for you as well. If you missed episode one, don't worry. We're going to cover the basics here. But you might want to go back and listen to episode one because we cover some of the fundamental biology that may help you understand what we're going to talk about today, even in more detail. So Matt, have you been, man? I'm good. I'm good. Before we get started, we got to think the sponsors. We do. Let's go straight into that. Yeah. It's important that we thank the sponsors because this podcast comes to you free. And we also get a chance to highlight some of the products that we love and have been using now for many years. Our first sponsor is Levels. Levels is an app that syncs with a continuous glucose monitor, which they provide, and interprets your glucose data for you. I've been so impressed by levels that I've recently joined the company as an advisor. By monitoring your blood glucose, levels allows you to see how different foods impact you. I've had fun running tests of my own, seeing how different foods impact my blood sugar levels. For example, I've learned that white rice and grapes really spike my blood sugar, whereas potatoes don't. As we've discussed on this podcast, having stable blood glucose is really important. Not only for your daily mental and physical energy, but also for long-term health. If you would like to try levels, you can skip the 150,000 people on the wait list and join them today by going to levels.link/sinclair. That's levels.link/sinclair. Today's podcast is also brought to us by Athletic Greens. Athletic Greens is an all-in-one daily green strength that supports better health and peak performance. It's developed from a complex blend of 75 vitamins, minerals and whole food sourced ingredients. It's filled with adaptogens for recovery, probiotics, prebiotics and digestive enzymes for gut health. They also have vitamin C and zinc citrate for immune support. I've been drinking Athletic Greens for a number of years now as a way to cover all my nutritional bases. I'm often traveling and sometimes my diet just isn't the best, so by drinking Athletic Greens every morning, I know I'm getting all the vitamins and minerals that I need to stay healthy. If you'd like to try Athletic Greens, you should go to Athletic Greens.com/sinclair and you can claim a special offer. They're giving five free travel packs plus a year's supply of vitamin D3 and K2. Vitamin D3 is important for the immune system and vitamin K2 is really important for keeping the calcium out of your arteries and putting it into your bones where it belongs. So again, go to Athletic Greens.com/sinclair and claim this special offer. Today's podcast is also brought to us by Inside Tracker. Inside Tracker is a personalized nutrition platform that analyzes data from your blood and your DNA to help you better understand your body and to reach your health goals. I've been using Inside Tracker for over a decade now and I'm the chair of their scientific advisory board. The reason I've long used Inside Tracker is because they provide the best blood and DNA analysis that I'm aware of. They make it easy to get your blood drawn. You can either go to a local clinic or like I do have someone come to your home that only takes 10 or 15 minutes. It's really easy and from there Inside Tracker presents your blood analysis in an easy to understand way. There are graphs and they give you diet and lifestyle recommendations that help you improve your blood biomarkers. Another feature that Inside Tracker has is their inner-age test which I help develop. The test shows you what your biological age is, how it compares to your chronological age and what you can do to improve that number. If you'd like to try Inside Tracker, you should visit them at insidetracker.com/sinclair and you'll get 25% off any Inside Tracker plan. Use the code "sinclair" my last name at the checkout. David, when we sat down together three, four years ago, we started mapping out this book and I said, "Look, I need you to give me one starting place." When we're talking about health advice, there's so much information out there. I need you to give me one starting place. You said immediately, "I know, the one thing. Let's start there today." It relates to this episode. The one starting place is. Four long-javit. Eat less often. Those three words. Eat less often. That is the one thing that will have the biggest impact on your longevity based on all the science we'll talk about today. This doesn't mean eat fewer calories necessarily. It can. That's good. That's good. But a lot of people struggle to do that to eat fewer calories. 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 adenine, 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 really what's happening here. It's not just about less calories. It's about what eating less often does inside of our bodies. Right. And we'll get to that. But really, 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. But 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. We're not fat-shaming anybody. But we're going through the science. This podcast is about what the science says, not what's socially acceptable. And it is true that if you're a leaner, you will live longer. That is a fact. It's not necessary to get benefits by doing what we're going to say. But also interestingly, as a side effect of eating less often, you will lose weight. I did about 15 pounds since the beginning of the pandemic. And I look better, I feel better. And it's a nice side effect. But ultimately, what we're going to do here is we're going to say, these are the kind of things you should consider in your lifestyle. If you get there, we're going to ease you into it. There are some tricks that make it easier. And ultimately, you're going to end up with a lifestyle and hopefully a body that allows you to live decades longer. We made the promise on this program to really stick to the science, let people know when the science is coming from studies involving animals, when the science is coming from studies involving human beings. And what we're seeing here is really important. Most fasting research has been conducted so far on model organisms. But what we're seeing in those model organisms is fairly universal. Well, it is. And the most reliable way to extend lifespan of any animal or even a yeast cell is to restrict its calories. And you started your career in yeast, you still study yeast. And one of the really big breakthroughs in understanding how to extend the yeast's lifespan came in your lab when you were studying what happens when yeast are calorie restricted. And that was the goal. The reason I went into aging research in part and while I was so optimistic about being able to have a big impact is that we know that restricting calories works on everything from a yeast to a spider, a fish, a worm, Labrador, pet Labrador and 2002. There was a great study that showed you could lengthen lifespan of the Labrador's from what was a 12 years to 14. I want to figure out how the heck this stuff works. How does this diet work? Because then we can bottle it. And we're basically at that point now. But to your point, just taking pills and sufficient. If you add the pills plus the diet, you get an additive doubling effect. So we're going to go through supplements in another episode. Today it's all about how to maximize when to eat and what to eat. And it's really important because look, not everybody can take supplements, not everybody can access the supplement. What we're going to talk about a lot of things, including things that you can do with $10 in your pocket and things you can do in $100 in your pocket. you pocket but this is something you can do with whatever you want. whatever you're paying right now for food. - Well, it saves money. - You can do it. - Yeah, you eat. - It doesn't save any money, like it's been less on food. - Right, and the kinds of food we're gonna recommend are fairly cheap foods. But getting back to yeast, I went to MIT to study this little fungus. It's a yeast cell you use to make bread and beer. It's microscopic. Put 10 of them together, you might see them as little dot. That's how small they are. But I used to love yeast. Literally, I would name them. They were little pets under the microscope. I'd follow them through their lifespan. - If you were a bull. - Yeah, I would get really sad when they would die after about a week. 'Cause I got to know them. I would spend 14, actually more, probably 16 hours a day helping them along in their life, taking away their daughters, which is how we count. - You know, David, if you love something, you really shouldn't take its children away. - Yeah, pretty messed up. - That's true. If you leave the daughters, unfortunately, there's about five million of them by the end of the experiment, and you can't find the original mother. That's the reason. - 'Cause these things, they divide and expand, and they expand and expand. They're exponentially right. So you gotta get rid of those daughters. You don't kill the daughters, you're just moving away. But what we found was that when you reduce the amount of sugar in the plate, so they eat glucose, that's what we gave them. Two percent glucose makes them live about 25 divisions, daughters. If you restrict that down to 0.5 glucose, so now down to 25% of that concentration, they will live over 30. And that's really cool, right? That you can just by changing the glucose levels, and we'll get to how that works in humans, very similar. You can extend lifespan. And what we showed was that there's a set of genes that controls that process. This isn't just just glucose hurting the cell. There's a genetic pathway that gets triggered by low energy. And these genes we talked about in last episode, they're called Sir Tuan's, and there are five of these genes in yeast and seven in our bodies. And they respond to low energy. They respond to other stresses as well, such as high heat, low amino acids, high salt. The Sir Tuan's will get activated by these, what we call, "hormetic effects." What doesn't kill them makes them stronger. And in this case, low energy led to the activation of these enzymes called Sir Tuan's. And then they took care of the DNA repair and also stabilization of the epigenome. - There's a lot there. We got to back and look, let's slow this down and pace this out. Let's start with Sir Tuan's. What's actually happening when, in the case of yeast, or any organism in this case, because it's very similar in mechanisms, right? What's actually happening with the Sir Tuan's, when yeast or any other model organism is calorie restricted is fasted. - Yeah, well, their role is to extend the lifespan. So what they're doing down at the very minute part of the cell is they're protecting DNA and making sure genes stay on when they should be on. But what's happening to boost their activity during caloric restriction, this low glucose level, we managed to figure out in the first couple of years when I moved my lab to Harvard Medical School, or started my lab at Harvard Medical School, we found that low energy activates a certain gene. It has a name, it's called PNC1. We have an equivalent gene in our bodies called NMPT. And turning on that PNC1 gene in yeast was able to activate the Sir Tuan's because that gene makes a fuel for the Sir Tuan's, called NAD. And so in our bodies as well, when we're hungry, these genes come on that make more NAD, this very small molecule that the Sir Tuan's need for fuel. And then they do the protection. They repair DNA and they stabilize the epigenome. - And this is sort of the beginning place that led to NAD boosters, where we started going, "Oh, well, if we can boost NAD in other ways." And that's not, we'll talk about boosters in another episode, but just to sort of put that in the chronology of how this revelation came about, and why so many people are now taking NAR and NMN? - Yeah, that came out of our lab. We found two ways to activate the Sir Tuan's synthetically. One was to use the red wine molecule, reds veritrol plus some other plant molecules that are now used in supplement market. And that was a big craze in the 2000s from our lab. And then the second one, which is now probably an even bigger craze, is the NAD booster. And a lot of people are shooting themselves up with NAD or taking NAD precursor supplements. You mentioned NAR and NMN will get to those in another episode, but you can mimic low glucose in these yeast cells by giving them these NAD boosters. Or you can turn on this PNC1 gene artificially and they live longer in all cases. And we found that if we deleted that Sir Tuan gene in the yeast, either one of them or multiple ones, then caloric restriction in the yeast didn't work anymore, which showed us, told us that this wasn't just glucose being bad for you, glucose doesn't hurt you. It's that the low glucose is activating the natural defense state of that cell, which we inherited, have inherited over the billions of years since we separated. People are just going to cut out that little part where you just say, glucose isn't bad for you. And you just can play that on a loop and it's going to be great. All right, well, glucose is bad for you, but not for the reason that you might think. So we have a little bit of understanding now of how Sir Tuan's are turned on by fasting. We talked about two other classes of longevity genes in the first episode, MTOR and AMPK. Do you want to go really briefly through how these genes are impacted when we restrict calories when we fast? The first one is MTOR, which stands for a mammalian target of rapamycin, the drug rapamycin. We talked a little bit about it in the last episode, but let's refresh everybody's memory. This is a protein complex in the cell that registers amino acids. When you have a lot of protein, you eat a big steak, it's going to activate this MTOR protein complex that allows the cell, causes the cell to build things. It's one of the reasons eating steak allows you to build more muscle, but that's not a recipe for longevity. What we know from many animal studies, even in yeast, if you down-regulate the activity of this MTOR protein complex, you get longer life. Why? Because it's activating a process called autophagy, which recycles proteins. So when you're hungry, this autophagy will get all the old proteins, put them in the recycling bin, and then bring them out as fresh proteins. And that seems to be really important for longevity. In fact, even if you just inhibit MTOR and stimulate autophagy, that's sufficient to extend the lifespan of flies and even my spike, dramatic amounts, even 30%. So in MTOR, we start with fasting. We get longevity in certain wins. We start with fasting. We get longevity in AMPK. Same thing. Same thing. But in a different process. Exactly. It's doing something else. And in this case, when you're hungry, AMPK will go up. AMPK, if you're wondering, stands for AMP activated kinase. And that's just an enzyme that responds to low energy. So when you're hungry, you'll make more of it. And one of the main things that it does is it makes more mitochondria. We lose mitochondria as we get older. And when we exercise, we get more. And this is a way of artificially stimulating that production. Why do we need more mitochondria? Well, they're important for metabolizing things that you eat. But one of the main things that they are used for is to make chemical energy. So when you activate AMPK, you'll feel better. You'll have more energy. And you also fight aging. And you're using the words "You" a lot here. You're going to talk about, like, you presumably the people watching and listening to this are human beings. But we should note that, again, much of this research got done in model organisms. Human studies are a lot tougher. But we have them for humans. We do have them for human. But there are fewer of them. And there are, like, most of the sample sizes are much smaller. Yeah, but there's enough known about both MTOR and AMPK to make pretty strong conclusions that these are beneficial to human health as well. For example-- But this is-- I guess what I'm getting at here, though, is the reason why. I think a lot of people would hear, well, all these animal studies were making all these conclusions on animal studies. And you don't have that many human studies. Human studies are-- they take a really long time. They're really expensive. Well, sure. And until this is 100% proven, many of us will be dead. So the point is, we're going to give people the information in this podcast, and in the notes, we're going to provide references. They can read more to make informed decisions about whether they're going to try certain diets, lifestyles, and even medicines and supplements. So what we know from studies of MTOR and AMPK search to ends is it tells ourselves the times are tough. This triggers this metabolic shift into a different form of energy. And all of that-- not all of that-- but much of that we know from animal studies. We mentioned before the majority of the research on lifespan extension comes from model organisms, comes from animals that aren't us. But we're not just entering. We're in a world right now where we're doing this research on human beings as well. We are. It's a fascinating time because we've got two worlds. And I walk in both worlds. One is there's clinical studies being done, some of which I'm involved in with NAD boosters at Harvard. We've been testing two years of those in humans. The placebo control double-blind trial. Like the goal of standard stuff. Right. And those go to scientific publications. But because people can read the literature and hear about things, there's this self-experimentation world as well. A lot of it on the west coast of the USA. And you hear stuff. And these are anecdotal. But they also are interesting anecdotes that guide the clinical trials. And it's this very interesting time where we're in, where there are parts of the population. Let's call it one percent of the US that is not waiting for the proof that this works But I do want to say before we move on that there is pretty good evidence that modulating these Defenses in the body in humans also works and should extend longevity But we're not just blind and you know, I'm not crazy Experimenting on myself and my father what we know actually is that drugs that inhibit mTOR RAPA MISON in low dose intermittent does mimic fasting and does boost immunity and does give biochemical changes that mimic fasting and predict longevity and there are people that are taking RAPA MISON again We'll talk about that in episode five But there's also metformin which is a diabetes drug and that activates Ampk and that's also by looking at tens of thousands of people who take metformin for type 2 diabetes Been shown to slow down the currents not just of diabetes, but other diseases of aging together Just those facts that I've told you make me convinced that Fasting and the drugs that mimic fasting are going to be important for long term health But also wellness in in your body today This is other way of knowing this other form of evidence for this that we haven't talked about yet That I think is important to bring up here You know there are there's the double blind and placebo controlled studies that are ongoing right now that are showing you know Impact and fasting all longevity There's like you say the experimental like really interesting like wow that guy's looking really good He's been fasting sort of thing right, but then there's these large populations and subgroups of populations all across the world who have fasted as a part of tradition and culture for hundreds thousands of years And there's there's pretty good evidence from from these groups as well Right. Well, let's name some of them the James the James in India in India that they're probably the Most well studied group and that there's scientific evidence that they have the most number of people over 70 in good health than any other religion Then any other group in India yeah, yeah, and a lot of people want to go Oh, well the James Rothden are also vegetarian But lots of people in India of vegetarian and the James are even doing better right than them Yes, and we'll get to the vegetarian diet and what the science says about that versus a meat based diet But there are other religions of Christians fast there's Ramadan for Muslims These are these are not just coincidences. These aren't just religious practices It's clear that humanity is figured out that you get you feel better you look better You ultimately our disease resistant you made it might even help cure diseases by going through these periods of being hungry or at least Not having food in your tummy why because it activates these three longevity defenses that we just mentioned Now let's get into these really interesting like sort of gold standard studies There is one out of the Baylor College of medicine. It was run by Isam Inda Koglu This was published just last year and it showed that Fasting from dawn to sunset for four weeks improved blood pressure reduced BMI decreased weights or conference and And this is the important part. I mean, it's all important, but it upregulated DNA repair proteins This is what we saw on all these model organisms as well Yeah, there are dozens of studies showing that fast periods of fasting are been is beneficial to people who are obese Not just because they lose weight, but they turn on their body's defenses. They become more insulin sensitive and their glucose levels come down Also showing that people of regular weight like me can benefit from from fasting. There's a number of studies there And these are all in the show notes if somebody wants to go and check them out But what's really interesting is that that certain diseases type one diabetes Multiple sclerosis even cancer those diseases seem to also benefit from fasting including when you combine chemotherapy With fasting you get this double benefit for many types of cancers And then the final point that I think's really interesting is you can mimic fasting Say midformin a number of doctors prescribe midformin to patients with prostate cancer because it More studies are showing that these mimic creed these molecules at mimic fasting or fasting or combinations of both Will help you beat cancer and to you when you see a bunch of different disease states being affected You don't think that what's happening is that each of these individual diseases is being played upon you think that the thing upstream The aging is being affected right? Yeah, well more specifically those three defense Mm-hmm components in the cell They take care of the body not just for aging, but to fight diseases in young people middle-aged genetic diseases Even something you might not think of like macular generation has been shown to be slowed down and even Reverse by fasting okay, so so far we've been really sort of broadly talking about fasting calendar restriction um But we haven't sort of talked about like what that actually means um, let's talk about because there's a lot I mean if somebody goes online right now because I like how should I fast they're gonna get a thousand different recommendations It's confusing for sure really confusing Do you want to do we want to just talk about like with some of these fasting regimens are for sure Let's let's do that and we talk about them in our book. So that that's also a resource I get questions every day from people How should I fast and my first answer is Well, you're an individual you've got a different lifestyle different tolerance for for pain and hunger Your female or male you've got different microbiome You these are really important things to take into consideration when we recommend things What we're saying is you can try this if it doesn't work for you try something else but also just to talk about us one of our sponsors inside tracker I use inside tracker because it's not just oh, I feel better today We actually have to measure things get a dashboard on your body to know if the the what you're doing whether it's exercise or in this case Your diet and when you eat is working for you And that's why I've been able to optimize my diet over the last 20 if in fact 30 years I'm not just guessing. I'm actually measuring measuring. Yeah, it's a little insane that the way that we sort of like wind about Testing out whether or not these different eating regimens were working for us is like Do I feel better? Do I not feel better? It's it's so vague. It's really nebulous Well, you wouldn't drive a car without a dashboard. So why do we do that for our bodies which are even more important? Yeah, bad habits. Yeah, that's what we do right that's what we've always and I feel bad. I don't feel good Yeah, well This is why I've auto pilot I drive a little crazy I do that with my body as well. It's all an experiment But let's go through the diets Okay, so that the fat that there's a fasting mimicking diet Volta-Longo colleague of mine from UCLA Is a proponent of that that's as a diet that lowers mTOR activity. It's low in these branch chain amino acids that I've mentioned Okay, and is that is that a diet that mimics fasting or does that include periods of actually not taking in any calories? It's both but you don't have to be as rigorous about the period The food itself will mimic it. So the food itself is Being processed by your body in such a way that the body is like I could really use a little bit more I could really like a little bit more yeah You want them to the body to be in a state of perceived adversity. Oh my goodness. I'm running out of food I'm not eating meat anymore because plants have less of these amino acids. So it it responds to that low amino acid input Volta's done some great work over the last few years He and his group have shown that on this fasting mimicking diet which they can send to your home That actually helps Cancer patients survive and get get over chemotherapy quicker again More evidence that fasting is good not just for longevity but for diseases. So that's one The next one let's talk about which a lot of people call intermittent fasting. We'll just call it fasting This is a period if you go longer than a day some people do three days some people go for a week I wouldn't go longer than that because then you'll start chewing up your muscle which you don't want to do But these long extended periods are Doing a real deep cleanse on the body and turning on that autophagy that process of recycling proteins very deeply Especially once you get beyond the three-day mark when your metabolism switches into what's called shaperone mediated autophagy the deep cleanse So that's fasting and then there's time restricted feeding which is what I do because I'm not very good at going beyond 24 hours Well, I think most people would really really struggle to get there Yeah time restricted feeding which is what what I do which is try not to eat till dinner That's hard enough. I'm my hats off to people like Peter Atea The doctor and podcaster who many of our audience will have heard of he can go for a week And he's he's got a lot of willpower if you've ever met the guy. He's different than me I'm more of a hiddenist but he is he grumpier at the end of the week Do you think then he is at the beginning of the week though? I mean like after all of that time He's always serious. That's that's what I can tell you But brilliant, but let's get back to the this 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 could remember here is that there's a period of sleep in which you are not eating and so Yeah, 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 me as an example of an average human being, because I'm pretty lazy and I'm not that driven. I prefer to take a pill, which is not the right thing. The, 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 that 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. And that's burnt off in 15 minutes. 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. We'll talk about the types of food later. But that gives my body this long window, more than 20 hours of not having glucose circulating from the external world. Now, what happens when you do that, and it takes a few weeks for your body to adapt, is that your liver will learn how to compensate for lack of food. It's called glucose neogenesis, the generation of glucose from your liver. And it actually overcomes the feeling of hunger. When you first get breakfast and lunch, you're going to be hungry. You're going to be nervous. You're going to say, "I can't do this in clear as an idiot." Well, this is why people fail at this is because they run into that and they think this is how life is going to be for the rest of the time that I'm on this diet. I can't do this diet. Right. But do it for at least two weeks because after the two weeks, especially by the three week mark, your liver has now learned that you're not going to break the stall lunch. And it will start making glucose at a steady level. That's really important because it's known that if you have these spikes of glucose, it leads to hunger when it crashes after a big meal. But also that when you get hunger, you eat. So you're in this wave of hunger or eating. Do you think people should ramp up? I mean, usage said do no breakfast and lunch for two weeks. But should they ramp up by breakfast first and let their liver get used to compensating for no breakfast and then add lunch? Well, I would skip one meal and then go for two. You can't do the whole thing. Most people will fail. But you're trying to avoid this thing I was just talking about called reactive hypoaglycemia is that if you eat a piece of toast for breakfast or heaven forbid a giant glass of orange juice, you'll have this spike in sugar and you'll feel great. But then your body will put out too much insulin and suck that glucose out of your bloodstream and put you into a glucose deficit. And that's hypoaglycemia. And then you're hungry. You've got ghrel and coming out into your body and you feel hungry and you need to eat something. I'm at a state though now where I don't get those rises and crashes. My liver is putting out glucose from when I wake up till dinner and I've never been so focused. I've never been so brain fog free because these crashes what they do is they make you feel shaky or tired and brain fog. And I wish I'd done this in my 20s and done it my whole life because I've really never felt better because of it. We can actually measure this now with continue of glucose monitors. Right. And this is a shameless plug to our one of our sponsors. I just know that it was not intentionally creating this moment for a shameless plug but we can. Yeah well let's mention them because it makes this podcast free. So levels provides glucose monitors that you stick them on your arm and they measure the glucose levels and I've used one of them. And what I found was there are certain foods that spike my sugar really high and then I get the crash and it's very clear that when I'm feeling jittery and hungry I am in that hypoglycemic state that comes after a big meal or even a piece of toast for me or a bagel. That's really important because then you'll learn what your microbiome and your body responds to well and not. For me I was surprised that white rice, toast grapes were really bad and potatoes weren't that bad. And so now I've optimized my diet to not have these periods even after dinner where I feel crappy. And not everybody's going to respond the same way. Like you said earlier, we all have different lifestyles, we've got different genes. Jim Nelson's work's been sort of informative in this. Yeah so Jim did an important study in mice again, not humans but it tells us that genetics is important because he took very similar mouse strains, strains of some called black six and then some white ones and he crossed them together to make a genetic diversity, a colony of about a hundred different types of mice and put them on the standard caloric restriction protocol which by recollection it was close to 35% of what a mouse would eat given food all the time, ad libidium we call it. And about half the strains of mice lived longer and then about a third of what the remaining ones lived shorter. And that was a shock because we thought caloric restriction always works. That's not true, it can depend on your genetics. And we've now learned that some strains of mice and probably humans as well are much more sensitive to this diet, these types of diets and you probably want to do it a little less than someone else. And you only do that, know that if you try it on yourself and measure things. Jim Nelson I like this idea that we're all just sort of lab rats running around trying things out right now. Well, I get criticized by some doctors advocating that you're not supposed to be experimenting on yourself. Even people say you shouldn't be allowed to have continuous glucose monitors. How dare you measure your body. And my view on that is well, we should ban bathroom scales if we're not allowed to measure our body. Well, I love the fact that you're doing this because I'm going to let you do it out of me and then I'm just going to wait and see what really works and what doesn't really work. And that becomes a starting point. But that is sort of like what you've been doing. I mean, what you've been doing for a really long time. And you've been pretty open with people about like, here's what I'm doing and here's what I'm doing right now. And it hasn't been consistent for 20 or 30 years. Sometimes you start and stop things too because it's working and it stops working or it feels like it might be a good idea. And it doesn't. That's what we're all doing. Well, I've made plenty of mistakes. I don't talk about my mistakes as much as I should probably. But I've had times where I ate the wrong things and ate too much and gained weight. And my inside track of results were horrendous. Did you ever make any mistakes and 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. No, you have to. 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, really you need to eat something, a bit of protein is known to take away the feeling of hunger rapidly. Yeah, it is what my buddy, the 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 going to 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, 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've trained my to produce enough sugar that I don't feel hungry anymore. And if I do, 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 you are going to never get hungry. Anybody who starts this, they're going to be hungry at first. Of course, they're going to be hungry. It's not easy. I'm not saying that it's going to be easy, but it's worth it. And there's an important point to make here. I mean, we sort of touched on at the beginning, but I think we need to circle back to it because it's so important because we're not talking about starvation. We're talking about intermittent fasting with adequate nutrition. That adequate parts are really important. Yeah. So the acronym would be, I find, all right, trademarked that one. I found, let's call it the new type of dieting. By the way, intermittent fasting, I learned about a month ago is the most popular diet in the US. We talk about it in the book that might be part of it. But yeah, it's important that we add the AN at the end because we need the adequate nutrition. And there's one sponsor we haven't mentioned, which is athletic greens. But this is true. The reason that I take a drink, athletic greens. You're really good at working these in. Well, they're important to us. But the important part is that the adequate nutrition is necessary. Otherwise, you're going to be causing more harm than good. So when I take athletic greens, I drink it in the morning, I know I'm getting all those nutrients that I might not get during the day. So now that we sort of set the stage for when we eat, which is really important, when. And we still have to acknowledge we have to eat sometimes. Somebody's gonna, you know, sometimes you're gonna, if you intermittently fast, if you're going, you know, 20 hours without food, you're gonna have breakfast or you're gonna have dinner. So yeah, there's gonna be something on your plate. It's really important also what's actually on your plate. And that's what this next half of this episode is about is what we should eat when we are eating. And maybe the best way to start this really though is to talk about what definitely shouldn't be, or not definitely shouldn't, there should be a lot less of on that plate. - Right, well the big killer is sugar. - Yeah. - 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 is 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 instead keep those glucose levels low and consistent, you won't get the brain fog. You'll get fewer proteins modified that'll lead to disease. And thirdly importantly, you'll actually stimulate your body's natural defenses against disease and aging. - So 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 it. - It's invisible, right. - Inside tracker doesn't pick it up. - Right. - Here's the point, you can quit something, but you don't have to be trichonin about it. I still like to steal 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 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 what we were talking about doing in 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, and 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, the defenses 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 carnivore diets are the best for longevity. - And for some people, a lot of the menos are appropriate? - Well, certainly if you're an athlete or you want to bulk up, there are short-term gains. You'll feel better if you eat meat. 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 start, 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. - And that's because of the inhibition of TOR. - In large part, yes. The certain ones also get switched off by high protein as well. - So aminos are important. We have to have them. If we don't have them, we die. But you can get aminos from plants, as well as from animals. - Yeah, it's funny when I say I've gone vegetarian recently. Which is a fact. - When are you going to get your protein? - Yeah, when 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 have to work a little harder for it. - Great. I want my body to work harder. It's good for it. It burns energy. 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. - So we're starting to go down and talk about vegetarian diet and plant-based diet here. We're going to talk about a lot of those different choices in many here. But I do want to take us back for just a second to what's happening. Like really what's actually happening inside our bodies when I sit down and I still eat meat, I haven't followed you down this path yet. I love the steak. When I put a steak on my plate and I eat it, what's happening? What are those amino's doing? - Well, before you get amino's out of meat, you need to digest it. And so the first step is acid in your stomach is gonna break down that meat into amino acids. And then your microbiomes can utilize a lot of them. And then those amino acids are also gonna leach into your bloodstream. So now you've got these amino acids circling in your body, circulating. And there are three ones that are particularly important to know about. It's lysine, isolucine and valine, also known as the branched chain amino acids. And these are used by the body to sense protein intake. And the sensor is this protein complex we talked about called M-Tore. And when there's lots of these three branched chain amino acids, particularly lucine, it'll be activated. And this M-Tore, the role is to say, wow, I've got lots of amino acids, let's build muscle, let's repair cells, let's do all good stuff. Which is why you feel good if you eat red meat and your microbiome can handle it. - Yeah, I feel great. I feel like I can fight a lion. - Yeah, you might have to fight a lion to get it. But what actually is going on that's deleterious is in the long run, is that M-Tore can do something even better for your longevity than build new muscle. It actually can turn on this recycling program called autophagy. And that is very clear. There's no debate as to whether autophagy is good for you or bad for you. It's definitely good. So what I think people could do is to, if they want to eat meat, go for it. But try to focus on plant-based food more often so that there are periods during the week when there aren't as many loose-syn, I solicin veiling molecules floating around in your body so that you have a chance for your M-Tore down regulation to recycle proteins. Now, why do you want to recycle proteins? You might say, well, who cares about recycling proteins? Well, Alzheimer's disease is a good example of proteins that get modified and accumulate in your brain. And it happens not just in the brain, but in all tissues, we have these old proteins that linger cause us to get old to malfunction. But it's reversible. And it's reversible by fasting. It's reversible also by having low levels of these branch chanameno acids, at least part of the week. Let's talk about these primarily plant-based diets. There's lots, I mean, there is vegan diets out there. You said, like, probably that's for many people, that's probably going to be the gold standard. But a lot of these plant-based diets have a little bit of meat in them. There's the Mediterranean diet. There's the Okinawan diet. - Lacto-ovogetitarianism. - Right. Lacto-ovogetitarian diets. Is there anything you want to say about these or should we talk about them as sort of an umbrella group? Do we call them like blue zone diets? - Yeah, well, let's talk about blue zones in a minute. I think what's interesting is that there was a really big study by the Adventist Health Group 2013. Let's talk about that. Because what they calculated was the chance of dying based on various diets. And these were thousands of people. And what they found was that what's called the hazard ratio went down the more vegetarian and vegan you were. What does that mean? Your chance of dying goes down. And the number goes from zero to one. Whereas one is you're pretty likely to die tomorrow. Whereas a low number, which is around 80, means you've got 20% less chance of dying on any given day with this hazard ratio. So the numbers are the following. Non-vegetarians are at one, if you call that one. Compared to that, the next best one was semi-vegetarians at.92 and Octolovo or Lacto-Ovo vegetarians.91. So about almost a 10% reduction in mortality, death. And then you get into vegans, which point A5. So there's 15% reduction in death. And then the best one was pesco vegetarians. So getting a little bit of meat from fish, probably the fish oils in there are beneficial. And then you're down to.81. So that's a 19% reduction in your chance of death at any given day, late in life. OK, now that's all caused mortality. But we can also now see this in biologic aging, because we now have clocks that we can use to measure our biological age. And there are studies now also that are showing that these diets are effectively reducing biological. aging as well. Right. And there are a couple of these. There's a one-year study looking at a diet of mostly vegetarian. But the one that I think's really exciting is one that just came out a couple of months ago that looked at mostly women on a Mediterranean diet plus exercise over two years. And they could now calculate what happens to your biological age over those two years, having switched the diet. And they had various recommendations. It's a very typical Mediterranean limit alcohol. If you have red wine that's fine, a little bit of fish, you only use olive oil as your fat and focus mostly on plants. That was their lifestyle. And then exercise was walking and smother weight lifting. That's the furio study. Yeah. Okay. So the interesting thing about this study, at least to me, the thing that jumped out of me is it came out of Juvena Missala's lab at the Cancer Institute in Italy. And like would you go like, well, why do people who primary responsibility to study cancer care about aging? And it comes back to this thing that you've been saying all along, which is that if we can reduce people's biological aging, we can cut diseases off where they actually start. Well, that's exactly right. That these diseases that we think are just diseases are mostly caused by aging itself. And that slowing down that clock by fasting or eating the right foods Mediterranean diet is now shown, not just to slow down the ticking of the clock, but probably reverses your age as well. That's a mind-blowing concept. You have to think about that for a minute. That it's possible by changing your diet to reverse your biological age. One of the diets that stands to do this well likely that I know you're a big fan of is the Okinawan diet. You were on the Okinawan diet for quite some time, right? Yeah, I was. The Wilcox Brothers wrote a book in the 2000s that I loved. And it's mostly carbohydrate. So there's a fair amount of rice, but probably could have done better with a bit of brown rice, white rice, and jacuzzi through the roof. But mostly what I was eating were Chinese or Japanese vegetables that I could get at the local market. So they're organic, fresh, green, full of vitamins and soy. Mostly it was that. It was a plant-based, soy-based diet with a little bit of fish. And I looked great. I felt great. And then my kids came along and we ate pizza for a few years. So it was great while it lasted. And if you look at the Okinawans on the island of Japan, they are arguably the longest-lived people on the planet. But they have other things that are good for them, things like social structure and exercise. They work until they're in their 90s or 100s. And none of these things happen and avoid. Right. But that lifestyle is probably the ultimate for human longevity. And we know this because if Okinawans move to say Hawaii, which a lot of Japanese did, then they don't live long anymore. You talked about lifestyle. This is a really big part of. You said you wanted to get back to the Blue Zones idea. You go across the world. You look at these communities of long-lived people. They have a lot of things in common. And we've been talking about diet today. So let's just jump to that. And there's been criticism of Blue Zones, too. Yeah. So Dr. Harriet Hall has said that those demographic data, people's ages, weren't actually correct. If you dig into it, they did a really good job. So Dan butinerer, I think, is right in saying that these people tend to live a long time. Out of hundreds of people that they checked the records of going back in the city records, there was one person that was misjudged. What was it that. They thought they were like 111 and they were actually 107 or something. Yeah, big deal. But that, of course, all studies have caveats. But this, I think, is really clear that areas of the world that have the right combination of foods, exercise, social structure, they do live longer. This is no surprise, even in yeast, when we don't give them social life. But when we modify their diet or give them food in a strict time-restrictive fashion, they also live longer. So I don't understand why even while it's controversial. There's one more idea about how we should eat that. I know you're a big fan of. There's less research behind it, but you believe. Pretty strongly, I'd say. And there is evidence, but I think it's still emerging and there needs to be more research. But this idea of xenohormesis, this idea of eating plants that have. Not just eating a plant-based diet, but specifically focusing on plants that have experienced stress. Talk about that. And why you are so focused on this idea? Well, the xenohormesis concept, Conrad Howitz and I coined this term in the mid-2000s, trying to explain why so many plant molecules are good for us. It just cannot be a coincidence. And we came up with this idea really prompted by a 2003 Nature Paper that we co-published that found that there were at least 20 plant molecules called polyphenols that activate the Sir-2 and Enzyme called Sir-1, the number one out of the seven family members. And when I looked into it, these polyphenols do remarkable things to the body. The one that got the most media attention because it's in red wine is Rizveratrol, but there's Pysiatanol and there's Fizitin and Chorsatin. These are supplements that people are getting excited about only now. But when you look into it, they activate an inhibit pathways or proteins in the body that are known to be important for health and longevity. And in some cases, the same molecule will inhibit one protein and activate another one in just the right way to promote health. That cannot be a coincidence. There's no way that that could just happen randomly. So the idea is that we've evolved mechanisms to sense when our food supply, the plants that we eat are stressed. Because it's like a really warning system? You know, we're humans. We can see that the plants are wilting and we know that the crops are dehydrated. We can measure the soil. Most organisms on the planet don't even have eyes. How would they know if their food supply is going to run out unless they sensed the stress, the fear in those foodstuffs? And so when you stress a plant, you get more Rizveratrol, you get more Chorsatin, Pysiatanol. And if you look at. What kind of plants we should say? I mean, it's not every plant that we're going to get those things out. Of course, it's every plant. It's every plant that gets stress. Well, plants are two engines and they need to survive just like we do. And they make these polyphenols in order to survive when they run out of a running out of water and nutrients. Okay, where are we going to get the most of those? Or even preyed upon by caterpillars. But in our food supply, a lot of plants have very few of these molecules. Why? Because we think that the faster they grow and the less stress that they have, the better. That's actually more profitable for a farmer to grow plants that grow really quickly and have no stress. But are they better for us? Absolutely not. So how do we know if a food has been stressed? Well, you can start with the generalization that if they're grown out in a field organically without pesticides, probably they're more stressed, right? But also there are foods that are intentionally stressed. Red wine is one. The best red wines are ones where the vines are dehydrated or have fungus growing on them. There's a good reason for that. We know that they taste better. Why? Because xenochromatic molecules are made along with molecules that taste good and are filled with color. Just it's the plant defenses. And so what I look for are plants that are organic, local and colorful because those are the ones that are most likely to have those molecules. In the case of red wine, choose great varieties that are stress sensitive. Pinot noir is one of the most sensitive. If not the most sensitive, great variety. And that's why it has the most residual of any other type of wine. Let's bring this all together now. There's a lot of information here. But there's sort of a checklist. And so let's talk about like if people are going to have like four takeaways here, five takeaways. Eat less often. You would say start with eating less often by skipping one meal a day and moving from there. Yeah. And don't snack. And don't snack. Avoid sugary drinks and foods. Okay. Eat less often when you do eat, kill the sugar. Yeah. I focus on, I try to eat artificial sweeteners and natural ones. So Stevie is a big one for me. And there are some others that are out on the market that are naturally occurring sweeteners. Okay. But working toward reducing your meat intake. If you're dieting, if you're diet is aimed at longevity, very likely you're going to 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. And we've got these references in our show notes that reducing the amount of red meat and in particular process meats is beneficial for long term health and even prevention of cancer. One of the things that's not appreciated about red meat, I'll just mention this is that it's not just that they have more of these three branch chain amino acids that prevents M-tore from doing its good stuff to the body. There's also 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, probably in people to enhance, accelerate cardiovascular disease. So I would say that the liver is a very important part of the diet. cancer too, right? Yeah. And so what we want to do is to limit the nitrates that preserve needs. If you like a good steak, by all means eat one. It's not going to kill you. But if you try to just push yourselves towards a more plant-based, plant-focused diet and maybe have some red wine occasionally, a lot of olive oil with a lax acidate, which activates certain as well. The Mediterranean diet is the one that I think is likely to be the most, 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. And 2000 or in 2000? The year 2000. It's 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 like it 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 over 80. So I don't know for a fact that it wouldn't work on 80 year olds. Sure. Right. But yeah, that's the point that's really important when often when I give talks to crowds, they are 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 are can have massive benefits. Some people say, oh, you need to have a carry a bit of fat on people that if you're over 80, you should have a little bit of body fat. There was there was a study that a lot of people latched on to that they got 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 when those studies had been read, have been redone, being lean as an as an older person is also beneficial. If you look at 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. Don't cut the meat and respond with like a bunch of carbohydrates. Eat the veggies. And if you are going to 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 if you 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 going to go back to that like second and third point, if you are going to eat sugar at the end of the meal, what you eat during the meal and in which order also makes a difference. Start with the protein and effect. 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. We're doing this really horrible thing to children by telling them that their lives are the sugars. This is really great thing that they should have all the time. They should be able to have snacks at a late and with sugar and so on. Breakfast that's our sugar. Yeah, well, I blame the food industry for that because they want to sell more food. And we've been taught that children should never go hungry. Breakfast is the best meal of the day. And we've got an obesity epidemic in kids. No surprise. And what parent doesn't feel guilty when their kid feels hunger. But for long term health, even programming the epigenum for long term health requires some hunger in individuals. And what we do to kids is we say, big breakfast. Here's a snack. Here's a lunch. Terrible lunch, typically at schools, public schools. Big dinner. Go to bed full. Wake up. Eat some more. We're not just causing problems for these kids' physiology for the long run. 20, 30 years later because their epigenum is now set for feast, not famine. But we're also setting up for obesity, which shuts off their survival programs right now. So their bodies are aging quicker than they otherwise would. I wonder if that's not a really important sort of frame to put what we call the obesity epidemic into is it's not just an epidemic of making people bigger. It's an epidemic of making people age faster. Absolutely. And we're going to see the impact of this in two or three decades from now with any increase of these diseases because the clock has been accelerated. So this is most of our listeners, most of the people are listening to this watching this are going to be adults are going to be making decisions for themselves. But much of this, if not all of this is really translatable to what parents should be starting to help their children develop the habits of eating in these patterns as well. And it's important that they're still hungry once in a while. Yeah. And not just have food lying around that whenever they want to snack they can. That is the way that we evolved. We have this metabolic winter hypothesis that we've published. When we were going back probably 100,000 years ago back to six million what was our lifestyle. We were cold and hungry. These days we live in air-conditioned and heated houses with food always available which goes against what we evolved to be optimal. And so we've got to go back to those days where occasionally we were hungry occasionally we were cold. We'll get to cold therapy later. But basically the concept if there's nothing else that you remember about this topic, just remember this that we need to put our bodies in a state of want for them to fight diseases and have ultimate health in old age and give us longevity. That's a really good place I think to stop for now because the next thing we're going to talk about is other ways to put our bodies into state's stress. That's episode three. Do you want to preview that just a little bit? Well there are certain things you can do. We're going to talk about exercise and cold therapy and so on as these are ways of making the body feel like it's in a state of adversity. And do very much what these what fasting and these diets do which is activate these longevity genes. That's exactly it and the exciting part about the world we live in now is we're learning what is the best combo of those things. And we'll talk about that in next week's episode. Thank you for joining us today. If you're enjoying this podcast and would like to support us, please subscribe on YouTube on Apple Podcasts and on Spotify. On Apple Podcasts you have the opportunity to leave us up to a five-star review. Also please support the sponsors we mentioned at the beginning of the episode. That's probably the best way to help us. We also have a Patreon account. It's patreon.com/DavidSinclair. There you can support us at any level you like. Thank you for joining us and we'll be back next week to discuss exercise, cold exposure, heat exposure and other acute stresses.