Stay Young Forever: Best Ways To Burn Fat, Prevent Cancer & Stop Cognitive Decline | Dr. Mark Hyman

I want you to imagine something. Imagine a drug company, pharmaceutical company, releases a brand new drug. And this is what the drug does. It improves blood pressure. It improves your blood pressure control and insulin sensitivity. It helps you lose weight. It dramatically reduces the risk of heart disease and lowers your cholesterol. It improves your mood, your motivation, your cognitive function. It also prevents dementia and makes you stronger, builds muscle and bone health. And if that wasn't enough, it also reduces the risk of cancer, many cancers like colon, breast, uterine and lung. And it also helps your sleep. And if that wasn't enough, if your sex drive is low or your sex function is waning, it helps with that too by boosting testosterone. And the best part, it's free and there's no side effects. Amazing, right? Now, people would line up around the block of every pharmacy in the country to buy this wonder drug. Except, you don't have to imagine such a powerful cure-all because it already exists. The only difference is it isn't in a pill, creating a lab somewhere on the planet, and no pharmacy can sell it to you. Because, guess what? It's exercise, that's right, moving your body. And it's one of the best habits you can possibly adopt to live a longer, better life. Now, I use a cartoon in my lectures that shows a doctor and a patient, and the caption reads, the doctor saying to the patient, Do you have time to exercise an hour a day or be dead 24 hours a day? So, I think it's not that far from the truth. So, let's talk about what are the biological systems that are improved by exercise? It has to be the right type of exercise, the right dose, the right frequency. And we'll talk about what that is. But it improves the health of your immune system. It boosts the number of your mitochondria, the powerhouse of your cells. It balances your blood sugar and your insulin, your adrenal glands, your thyroid, your sex hormones. It helps you improve detoxification, your circulation, your lymphatic flow, and even optimizes your microbiome. that's right, your gut bacteria. It also does some amazing things about the hallmarks of aging. Now, in my new book, Young Forever, here it is, everybody, super excited about it. It's out February 21st. And in the book, I talk about something called the hallmarks of aging. We've covered on the podcast a little bit. These are the things that go wrong as we age that underlie all disease. If we cured all cancer and heart disease from the face of the planet, we might extend life by five to seven years. But if we address the hallmarks of aging and the causes of the hallmarks of aging, we might get 30 or 40 years of life extension. And you know what the deal is about exercise? It addresses many of these hallmarks. For example, it increases telomere length. It reduces inflammation. It improves your mitochondrial health. It impacts your nutrient sensing pathways like insulin signaling and mTOR and AMPK and sirtuins, things we've talked about. It also improves your epigenome and reverses your biological age. Now, you might be going, oh, what do I have to do? Run a marathon every day? No, you don't. It doesn't take a lot of exercise. Even starting with something as simple as 10 minutes a day can add a significant benefit to your health. And if you do more, more vigorous exercise, interval training, strength training, you can extend your health span by leaps and bounds, literally. You can stay fit and strong and functioning well into your 80s, 90s, 100s. I just read something pretty interesting that right now there's about half a million centenarians around the world. And pretty soon by, I think 2050, there'll be about 3.5 million people living over 100 years old, which is pretty amazing. There's two of the oldest people now around about 115 years old. So many of us will be able to reach that age. So if you look at what you need to do, combined with diet, exercise is really the most powerful tool for staying healthy and extending your life. My mom used to say, whenever she had the urge to exercise, she would lie down till it went away, which I think she got from any young minister or some comedian. But, she followed that advice, unfortunately, and she didn't exercise, despite my hounding her. Of course, parents never listen to their kids. I mean, kids, whatever, something like that. Parents never listen to their kids. And she ended up being pretty frail and disabled the last decade of her life and not too functioning. So when you start thinking about how to take this approach of incorporating movement and exercise in your life, you can get really amazing benefits. I'm just gonna kind of go through them 'cause they're just so profound. It, it, it actually unlocks the body's longevity switches, the regenerative and reparative systems that are built into our biology. It activates all the longevity switches that I talk about in the book, particularly the four that have to do with nutrient sensing pathways that are sort of meta to everything else. Insulin signaling, mTOR, which is really important in terms of autophagy and cleaning up your cells, sirtuins, which are important in DNA repair, and also AMPK, which helps regulate blood sugar, insulin sensitivity, inflammation, and many other things. So it's pretty darn exciting. It also activates the body's antioxidant systems. It improves your cognitive function and your mood. It supports, I mean, they found that just walking helps prevent dementia, which is pretty cool. It supports your microbiome. It reduces inflammation. It helps you produce more mitochondria and help them work better and be more efficient and have better function because mitochondria is where you make energy and as you get older, you lose energy, so you want to boost that. It also keeps you strong and functional. You know, I just came back from skiing. out in Switzerland and I had a really great time. It was a privilege to be able to go there. And I was amazed. Like I was just skiing along like I was when I was 30 or 40 and I was probably going a little too fast, but you know, I like to do that. And, you know, I felt strong and able to do it and it was keeping up with people half my age. So I think the body has the capacity it needs to do this. It also makes you happier and improves your mood and even improves your sex life, believe it or not. so what does the research say? And let's talk about some of the, the nitty-gritty about how it works. If you really, you know, maybe you want to know about the science. Maybe that'll motivate you. I probably doesn't motivate most people, but it kind of gets me all excited. I kind of like that. I'm a little weird, but it really, the research is just, it's just unbelievable about exercise. When I started to dig into, you know, obviously you can look at exercise and anything and search on, on PubMed and learn about it. But I started to look at exercise and Longevity and what it does. So we covered a little bit of this, but I want to sort of expand on it. It improves your telomeres, which is a little caps at the end of your chromosomes that start to shorten as you get older and shorten your life. It actually lengthens your telomeres by exercising. It protects your telomeres. It optimizes all these longevity switches like AMPK, which regulates blood sugar. People say, I'm gonna take metformin for longevity. Well, exercise is way better than metformin for regulating AMPK. It also activates sirtuins, which help DNA repair, reduce inflammation, and improve your blood sugar control, which are really important. It also improves your cardiovascular and heart health, we all know it reduces the risk of heart attacks and strokes and improves your brain function and cognitive function. It also helps certain types of cancer, as I said. We see the regulation of our biology through exercise being meted through all these mechanisms have to do with immunity and cancer prevention. So it's super great. And of course, it extends your health span and your lifespan. I remember being in Sardinia and I mentioned this guy, I think before, but his name is Pietro. He's 95 years old. and he was like a shepherd and he was just running up and down the mountains all day, five miles a day in this really regular terrain. And he was bolt upright, you know, booming voice, clear eyes, you know, strong and, and mentally sharp. And I was like, wow, this guy's 95 years old. You know, most people 95 in America barely can kind of walk across the street or get from their bedroom to the bathroom. And here he is, you know, running up the mountain. So we have the ability to do that. And he exercised every day as a shepherd, not, quote, exercise, but he just, that was his life. It also, it's incredible for diabetes, for blood sugar control. I mean, just walking after dinner is a great way to keep your blood sugar down, helps you become more insulin sensitive. And, and very importantly, it helps you build muscle mass and function because as you get older, you lose muscle. It's called sarcopenia, and that leads to all these hormonal and metabolic changes that accelerate aging and lower testosterone, high, high cortisol, the stress hormone, higher blood sugar, worsening cholesterol. I mean, just lower growth hormone and increased cortisol. Like I said, it's just, it's really bad news. So building muscle is really important, and that's clearly only done by exercise. So hopefully listening all this, you realize you can't afford not to move. My basically philosophy is if you don't move, you won't. Literally, you'll be dead. So how can you actually incorporate more movement? What can you do without having to drag yourself to the gym? Now, I go to the gym sometimes, but I rather play, and I. I think. There's a lot of options and you can just do simple things like, start with simple things, even five minutes a day. And if you don't have five minutes a day to do something, there's something wrong with your life. So you better look at that. So, you know, for example, I, I, I figured out I couldn't do a 10 pushups when I was 50. So I, I started, I'm gonna do pushups. So I take a shower most days. So I basically would wait for the shower to heat up cuz it was, it's, I live in a barn and it's really tall and takes a while for the hot water to get upstairs and I would do pushups and I went from being able to not be able to 10 to be able to do almost 100 push-ups without stopping. So we can train our bodies and it's really simple. Or maybe while your coffee's brewing, maybe do some stretching and yoga. Walk or bike instead of driving. In many countries they do this. I just met this guy who was a CEO of a big company and he lived in Switzerland and he runs a $6 billion company and he rides his bike straight up the hill or the match and say the mountain to work 2,000 feet elevation every day. And he's in incredible shape. He's 53 years old and his VO2 max, which is a measure of fitness, is that of a elite athlete and someone who's like half his age. So it's very impressive. You don't have to sort of, you know, do something like that, but just, you know, parking further away in the parking lot, taking the stairs instead of the elevator or the escalator, just simple things to start moving. Also try standing desk. or a stability ball. If you're, you know, at a desk, you sit on a ball. It kind of helps you move and move your body and increase your core strength. I have a friend, Mike Roisen, who was at Cleveland Clinic with me, and he used to have a treadmill desk where he, little, he was on calls and working and working on his computer and walking all day long, which is impressive. Make your leisure time active time. So if you're watching TV or movie, maybe put a stationary bike in your house. I remember I worked in Idaho as a family doc. and there was this patient that came in and she lost like a hundred pounds. I'm like, what happened to you? And she's like, well, I decided instead of sitting in front of the TV and eating all day, I would get a stationary bike and just ride the bike all day instead of eating. And she did. And she lost a hundred pounds. So pretty impressive. Maybe also you can, you know, listen to podcasts and, and an audiobook or do something like that when you're, when you're exercising or taking a walk and just. makes it more fun and motivating. And also do it with somebody else. As my friend Rick Warren said, everybody needs a buddy. So, it's important that if you maybe are having some trouble getting out there and doing stuff, find somebody else to do it with. It's much more fun for me to play tennis with somebody else or play basketball or go on a bike with somebody else and do it by myself. So, I try to do it with friends and it's way more fun. Maybe pickleball is the latest craze. Join a pickleball league and go outside and just do fun stuff. So these are just a few examples of how to incorporate movement and exercise in your life and simple natural ways to do it. And it doesn't matter what you do, it just matters that you do it. So according to science and particularly the science of longevity that I talked about in my book Young Forever, go get a copy please. It's really amazing. I like it a lot. It's one of my favorite books I've ever written, maybe the favorite because I think I'm obviously more interested in this because I'm getting older. It's such a an essential part of longevity and of health in general and just of enjoying life. It's not about doing it now for some result later. It makes you feel better now. And we really can't afford not to exercise. So start where you are. Build up slowly. Even 10 minutes a day of walking can help. Start strength training, weight resistance training, whatever, whatever you want. Body weights, bands. I use bands mostly because I travel with them. Do more movement throughout the day. What are the essential elements of eating well? Let's talk about what's important. Now, you can do everything else right. You can exercise, you can meditate, you can sleep, you can take all the supplements, but unless you focus first on food, the rest of it's going to be really hard. You can't exercise your way out of a bad diet. You can't meditate your way out of a bad diet. You can't sleep your way out of a bad diet. And so we have to come up with a framework that makes sense for guiding our choices. And the Pegan diet is basically the approach that I've created. And it's really a flexible, inclusive framework. it's built on a few key principles. And these are central principles, no matter what nutritional philosophy you ascribe to. I think they're universal. First is focus on quality. The quality of the ingredients, the quality of the nutrients, the quality of the food you're eating matters so much. So, you know, is a sun ripened tomato off your vine at the end of August in an organic little garden you have in the backyard. better quality than a industrially produced tomato that's designed to fit in a box and not squish and lasts for months on this shelf and tastes like cardboard the same. No. Focus on quality, whether it's real food or whatever you're eating. Try to get the highest quality, most nutrient dense food you can. And obviously that means no ultra processed food. Understand that food is information, that it's medicine, that it's instructions, it's code. that programs your biology with every bite. So you must understand that you're interacting with things not just from an energy perspective, not just fuel to run your body, but instructions that code for every single function of what's going on in your microbiome, your metabolism, your brain chemistry, your immune system, everything. And I could go on, the list goes on, is regulated by what you eat in real time. And the last principle after quality and food is medicine, and information is personalization. Not everybody needs the same diet. Some people do better on low carbs, some people do better on low fat, and some people do better on paleo, some do better as vegan. So we have to see what works for you and we have to be smart about it. But you want to make sure you eat a diet that is very much focused on these principles. And it also follows a few other things. One, it should be low in starch and sugar, low glycemic, super, super important. I can't stress that enough. I've said it forever, but is really important because that drives so much of the age-related diseases. Two, it should be full of good fats, avocados, olive oil, nuts and seeds. If you're tolerant of saturated fats and you don't eat them with carbs and sugar, you can have coconut butter, coconut oil, and even grass-fed butter or ghee. And make sure you eat foods that are full of phytochemicals, lots of colorful plant foods with anti-inflammatory, detoxifying, hormone balancing, energy busting, gut healing compounds. And, that's a nutrient dense diet that's full of longevity rich, I mean longevity producing phytochemicals, polyphenols, which are plant chemicals, antioxidants, microbiome healing fiber, probiotics, prebiotics, postbiotics, all of it. And, this is designed to basically regenerate human health and planetary health, which is something you can't separate. So, our health is intimately tied to the planet's health. Our own health is tied to the soil health, the nutrients of soil are how we get our nutrients. So it really is a beautiful ecosystem that we learned mostly how to destroy. But today I'm going to talk to you about how would you follow the Pegan diet? What does it look like? First of all, it's a plant rich diet, not a plant based diet. And that's an important distinction. Plant based implies vegan. Plant rich means your diet's mostly plants. and that should be three quarters of your plate covered with colorful veggies. Lots of colors, weird things, mostly non-starchy veggies. I do eat a purple sweet potato or sweet potatoes fine. Winter squashes are fine, especially if you're not insulin resistant or diabetic. Try to choose organic or regenerative when possible. Use the Dirty Dozen guide and the Clean 15 guide from the Environmental Working Group. That's ewg.org. download those guides and you'll learn all about which are the foods you want to stay away from that are the worst contaminated, for example, don't ever eat strawberries unless they're organic or nectarines, for example, whereas you can eat avocado or banana if it's not organic. Also load up on the good fats. What should you be eating? Well, nuts and seeds. Try to eat fats in their whole food forms, seeds and nuts, avocados, pasture-raised eggs, fatty fish like mackerel, sardines, herring, anchovies. some mild salmon that's small. Olive oil also is a very minimally processed oil. Try to stay away from the hexane extracted deodorized solvent, you know, mixed refined oil oils that we eat are primarily refined oils. If you're going to eat canola or soybean oil, I don't highly recommend that, but they can be part of cooking and other things if you want. And only if they're expeller pressed, only if they're organic. mostly their GMO, mostly their splayed with glyphosate. You just stay away from that. So for cooking, I use extra virgin olive oil at for for no heat or low heat, avocado for higher heat, avocado oil. I like that. And extra virgin coconut oil. Also use nuts and seeds. They are tremendous. They should be every day a couple of handfuls of nuts and seeds really help with weight loss, diabetes, heart disease. They're a great source of minerals, fiber, fat, protein. and lots more stuff. Almonds, walnuts, pecans, hazelnuts, macadamia nuts, pumpkin seeds, hemp seeds, chia seeds, sesame seeds are all great. I like pine nuts too. I put that on there. Also, what about meat? Should we be vegan? Should we be carnivores? Should we be paleo? You know, we do need protein and we need animal protein, especially as we get older to build muscle. If you don't have enough protein in the right forms with the right amount of leucine, which is a very important amino acid to build muscle, you will lose muscle as you get older. And if you see people who are vegan as they're older, they tend to be more frail, more thin, less muscle mass. And muscle mass is the currency of longevity. So you want to make sure you keep, maintain and build muscle as you get older. And so it doesn't mean you have to be eating, you know, 20 ounce steaks. It just means you need 30 grams. And that's not much. It's a palm size piece of protein or equivalent at each at each meal. So, make sure you're using regenerative meat if you can. There's a company called Force of Nature, which sources regeneratively raised meat from around the country or even around the world. It's really good for you. It's full of phytochemicals. It's raised in humane ways, harvested in humane ways. So, it's really a beautiful way to support a growing food system that supports regenerative agriculture. If you can, you can get grass-fed. pasteurized, organic when possible. Also, making sure that if you are plant-based and vegan, you may need extra protein powders. And you're going to be having processed food. It's processed food, which is processed protein powders. You're going to have ones that are just more from whole ingredients, but you have to make sure they have added amino acids, particularly leucine and particularly branched-chain amino acids, because you will not be able to get enough by just having the basic plant-based protein. When you also look at fish consumption in the addition of meat, it's great source of protein, but I would stick with the small fatty fish, sardines, herring, anchovies, mackerel, small wild salmon, high in omega-3s, low in mercury. There's a great company out there called SeaTopia.fish that's sourced for generally aquaculture raised fish. It's low in toxins, tastes great, low in mercury and full of omega-3s and actually great plant-based phytochemicals that come from the feed they're eating. So, check that out. If you want to learn how to lower your intake of more toxic fish, go to Environmental Working Group. You can use the Monterey Bay Aquarium Guide or the NRDC Guide for a low mercury fish. Grains, what about grains? Well, whole grains are fine for most people. I wouldn't be eating six cups of brown rice, which is 30 grams of protein. but small amounts of half a cup to a cup can sometimes be fine if they're whole grains, if they're more ancient grains, if they're not bred to be super starchy. So, I would encourage you to eat weird grains like heirloom grains, Himalayan terry buckwheat, ancient forms of wheat if you're not gluten sensitive like einkorn, emmer, or farro, but don't have them ground as flours except some of them may be okay like Himalayan terry buckwheat, a small amount of flour can be fine. But, you want to make sure your you're actually eating a low glycemic, protein-rich, mineral-rich form of whole grains, not the ones that have been hybridized and processed in the ways we eat them. So don't eat whole grain flour. Don't eat flour products. And try to avoid gluten, especially in America, because there's many reasons. You know, most gluten in this country is grown with dwarf wheat. It's sprayed with glyphosate at the end. super starchy. It has way more gluten proteins that cause celiac or non celiac gluten sensitivity. So I'd really reduce that sugar, obviously, you know, stay away from that stuff. I mean, a little bit's fine here and there, but as a staple, it should not be part of your diet. It's occasional treat as a recreational drug. And also just remember, below your neck, your body can't tell it between a bowl of sugar and a bowl of cereal or a bagel. Also, oils eliminate most of those refined oils, all those, especially corn and grape seed and sunflower. If they're LakE, they can be okay. If they're, you know, expeller cold press, they may be okay. But stick with the main oils that come from olive oil and avocado oil. You'll be doing fine. And dairy. What about dairy? Well, dairy, you know, it typically is raised in this country with a homogenous, not homogenized, but homogenous genetic cow, which is the Holstein cow. And that's A1 casein. It's very inflammatory. They're pump full of hormones, growth hormone, they're often milk while pregnant and you get, you know, flood of hormones and inflammatory compounds and inflammatory forms of casein. And if you want to have dairy, try sheep or goat, try A2 cows, which you can get like Guernsey and Jersey cows or A2 cows. And if you have the wrong kind of dairy, it's going to drive inflammation, cancer, osteoporosis, believe it or not. Yes, it's not good for your bones. That's a whole nother conversation you can I think read my blog called Six Reasons to Avoid Milk and where you can go on and read about David Ludwig's article on Medium on milk, which he reviewed all the literature recently about it and it showed that it really is not a health food. I recommend mostly avoiding it. Occasional grass-fed, you know, sheep or goat cheese or yogurt or milk can be fine. Ghee is fine because it doesn't have the milk solids in it. So grass-fed ghee is also fine. so that's basically it. Eat real food, personalize your approach, think of food as medicine, focus on quality, you can be super flexible and all that, and hopefully you can follow these principles and activate your body's own healing response. Hallmarks of Aging, these phenomena that scientists have come to understand are at the root of all diseases of Aging, heart disease, cancer, diabetes, dementia, the things that spending billions of dollars researching to try to find the cures for we're never going to find the cures for because we're not looking in the right place for the solution. Where we should be looking is at these root cause problems that go wrong as we get older that we can do something about. Now, I have a little bit of a different perspective than most longevity scientists about these Hallmarks. The Hallmarks are really important because, for example, if we cured all heart disease and cancer just got rid of it from the face of the planet. We would maybe live another five to seven years. If we address these Hallmarks of Aging, we might extend life by 30 or 40 years, which means living to 120. Now, that's good. But the question is, if the Hallmarks are at the root of all Aging, what's at the root of the Hallmarks? So we really don't have to become decrepit and. and dysfunctional as we age. We can actually maintain our energy, vitality, function very, very old if we know what to do. And the reason I go through these Hallmarks in the book is because it's important to understand why we age, what's going wrong, how do we work on it? What are the reasons why we have to do the things we have to do in order to increase our health span and our lifespan? And once you understand that, you're more motivated to go, oh, geez, if I do this, it's going screw up this Hallmark, you might think twice about it, and then you're empowered to deal with the root causes of it as well. So what are the Hallmarks? Well, scientists talk about 9-10. I talk about 10. I added the microbiome because it's super important, and many others do as well. So there's the underlying mechanisms or Pathways that are involved in Aging. They're influenced by the others. They're all interacting. There's not necessarily all separate problems. They are. kind of dynamically connected like a web. And functional medicine is about understanding the body as a system and treating the system, not just the symptoms. So, and understanding the body's a network. It's basically a network of networks. And so these Hallmarks of Aging are parts of these biological networks. And they're often themes you might have heard about in functional medicine, like inflammation and the microbiome and mitochondria, and there's, and there's more right in, in metabolic issues. It's super important to remember that we can influence these Hallmarks of Aging through dealing with the root causes of them. And there are also drugs and supplements and nutrients and lifestyle practices that also influence them. But it's not going to be solved by finding the drug for each of these Hallmarks. That is often what science likes to do, is be reductionist. But if you deal with the root causes of these Hallmarks, often most of them will change or get better improved. Now, we may need to go intervening in some of them here or there, but that's okay. So let's talk about what these are, how how do they work, what goes wrong, what causes them to go wrong, and then how do we begin to think about actually improving them so that we don't accelerate these hallmarks of aging. So what's the first one? The first one, I think, is the most complex. It's often the one that is influencing all the other ones. So I like to talk about it first, and this is called disrupted nutrient sensing. And we can, we can also think about it as disrupted hormonal and nutrient signaling. And essentially there's, there's four longevity switches that are sensing your environment all the time. They're sensing nutrient levels, they're sensing levels of amino acids, of sugars, protein, and they're either turning on or off and that influences our aging process. So a number of years ago, I was at a conference with Lenny Guarente, who's a scientist at MIT who discovered sirtuins along with David Sinclair, which are these regulatory pathways, one of these longevity switches. And he found that, you know, if you could actually properly activate these sirtuins, you could extend life by a third in animal models, which is pretty cool. So I said to him, I said, Lenny, what's really the deal with these sirtuins and what is causing them to sort of accelerate aging when they're not properly regulated. He said, well, sugar was basically his answer. And I was like, wow, that's pretty amazing because it's what obviously we know causes most of the chronic diseases. But I didn't realize it was so connected to these aging Pathways. So we, we basically sense all these things from moment to moment in our chemical environment and We either can activate the longevity switches in a way that makes us live longer and be healthier or regulate them in ways that are causing us to have more disease. And if they're really, it's really important to understand that at the root of these, there's a lot of this process we call autophagy. Autophagy is self-cleaning, self-cannibalism. It's how we recycle old proteins. We also need to understand that we need to build new proteins as we age too. We need muscle. We need to make all kinds of proteins for our immune system, our structural system. So you want, you know, the construction crew and the demo crew both, right? The recycling crew and the building crew. So how do we begin to think about these? What are these longevity switches? Well, there's four. One is insulin signaling, which is really important. And this is the one that gets overstimulated. The overabundance of sugar and starch overstimulates insulin signaling pathways, and that leads to more belly fat, more inflammation, lower sex hormones. cognitive impairment, dementia, obviously diabetes, cancer, heart disease, all are driven by these accelerated oversupply of sugar and starch in our diet, which is about 60 plus percent of our calories is ultra processed food and sugar and starch. It's really, really bad for us. I don't know how to say it either way. I've written many books about this and it's it's just one of those things that we can't ignore if we want to live a long, healthy life. So the key is to not overstimulate that pathway and basically below the neck. your body can't tell the difference between a can of Coke and a bagel. So make sure you understand that flour and sugar are the same when it comes to your body below the neck, obviously, and that you want to limit those in order to not overstimulate the insulin signaling pathway. Second is the mTOR pathway. The mTOR pathway stands for mammalian target of rapamycin, which is named after a compound found on the island of Rapa Nui in Easter Island that seemed to be involved in various things like is an antifungal, but not very good one. Also regulates the immune system, which is why it's used in transplant medicine. But it also seems to inhibit mTOR. And inhibiting mTOR is a good thing because it stimulates autophagy. Autophagy at night, for example, when you're not eating, will clean up and recycle things. It's super important longevity. And one of the things that we know is that calorie restriction extends life. It's one of the few things that scientists have found that it can extend life by like a third and is reproducible over and over in animals. So basically you restrict your calories by a third and you extend your life by a third. Now, you'll be miserable, but it works. So how do you do that without actually having to starve yourself? Well, that's why things that inhibit mTOR are really good, like overnight fasting or time-restricted eating, but even drugs like rapamycin can do that. So you want to do that for sure, but you also need to stimulate in the right way. So if we're always eating and eating all the time, that's what we do in America and most of the world increasingly now. And that overstimulates mTOR, and that can lead to cancer and all sorts of other problems when you overstimulate it. And it also prevents autophagy. So you want to stimulate in the right way. by actually building muscle through the right kinds of amino acids in the right time, in the right way. And I go through all that in Young Forever. But you also want to give breaks from stimulating mTOR through overnight fasts or time-restricted eating or even certain medication potentially like rapamycin, even things like this new fatty acid called C15, which is pretty cool, comes from dairy. And it actually, well, it's a newly discovered fatty acid. It's been around for a long time. We just figured it out recently. And this also can inhibit mTOR. So, there's a lot of ways to do this through supplements, through medication, through fatty acids, through diet. But inhibiting mTOR periodically is very, very important. So, you want to sort of the Goldilocks problem. You don't want to overstimulate it too much. You don't want to inhibit it too much because if you just don't eat all the time, you're going to starve to death. So, it's really about that Goldilocks perfect amount. That's mTOR and insulin signaling. The next two pathways are AMPK and SIRTUINS. Now, AMPK is a pathway, you know, identity monophosphate kinase is essentially a enzyme that detects low levels of energy. ATP is your body's energy source. When it gives up phosphorus, it becomes AMPK instead of ATP AMP, which is adenosine monophosphate instead of triphosphate, a little bit technical there, but basically the idea is you're giving up a couple of phosphate molecules and your cells detect that. They go, oh, I'm starving because there's not enough food, so I better do things to make myself live longer and preserve things that need to be preserved and reduce inflammation, improve my mitochondrial function, activate DNA repair and improve insulin sensitivity and all these things that have to happen as we want to age well. So we want to make sure we're properly regulating that. And that's really also by not overstimulating by sugar and by very much the same kind of things we just talked about. And there's also supplements and herbs that do the same thing. And metformin, which is one of the drugs that's being studied for longevity, actually works on this pathway, MPK. So I would say I'm not a big fan of yet. Maybe I will be. I'll, I'm open to changing my mind. But based on the data, I, I think lifestyle is a far better regulator of AMPK than, than is metformin. It works, but. compared to what? You know, like that's the question, right? Compared to what? So I think the next pathway is SIRTUINS. And this is the final longevity switch I call longevity switch, which is activated by NAD. You might have heard about NAD or NMN or NR. These are various things that the body uses to stimulate SIRTUINS when there's a low energy state to activate DNA repair, to shut off inflammation, improve insulin sensitivity, and it's really improving mitochondrial function. So sirtuins are really important and might have heard resveratrol being involved in longevity, which comes from red wine. Don't drink, please, to do this because they gave the rats 1500 bottles of red wine equivalent in terms of resveratrol. You don't want to do that. You'll die of liver failure, certainly before you live very long. But the key is that there's various phytochemicals that will activate these pathways. And a lot of this I talk about in my book, what are the foods you can eat? What are the phytochemicals that do this? And how do we regulate these pathways. So really important to understand that diet and lifestyle play a huge role. Also, a lot of the hormesis therapies, we're going to talk about hormesis in an upcoming podcast, which is basically the idea that what doesn't kill you makes you stronger. So using hormetic strategies can also activate these, whether it's cold or hot therapy, whether it's exercise and so on. Exercise works through many of these pathways as well. And we know exercise is basically the fountain of youth. So there's a lot of ways we can use the science of lifestyle, of phytochemicals, even certain medications to regulate these four nutrient sensing pathways and address this hallmark of aging and help us extend life. Really, really important. So make sure you're eating plenty of phytochemicals, lots of veggies, and making sure you're having the right timing and balance of protein, the right quality of timing of eating. So all this is, by the way, in the book in a very specific way. So I encourage you to check it out. so that's that. I literally could do a whole podcast just on the hall, on the first Hallmark of Aging, but I want to cover all of them without kind of boring you too much. The second Hallmark is something you're probably aware of, which is DNA damage and mutations. This happens all the time. Every day we get a death by a thousand Cuts, literally a hundred thousand little hits every single day. And our DNA has to repair itself. Now, even if you repaired 99.9 of your DNA every day, which we do, there's still kind of this Rogue DNA damage. And over time, those accumulate, they accelerate, and they affect our reproduction of new cells and our mitosis and our ability to actually replicate the things we need to replicate. So, you know, basically it's kind of wild, but, but, you know, their DNA is required to create all the things our bodies do, and it's basically the blueprint in each cell. And, and your DNA reproduces basically 10 quadrillion times. every time through cell division over your lifetime. That's an enormous amount. And it's like a copy machine. And there are glitches on the copy machine. And then your DNA blueprint can be produced with these glitches. Well, what do you do to address that? First, you wanna avoid the things that cause DNA damage, which is what we just talked about, the sugar, processed food, all that crap. Environmental toxins, radiation, by the way, stress also will do it. And second, you can activate your DNA repair systems. And the beautiful thing about the body is it has these innate healing systems. It's got its incredibly deep wisdom of what to do to heal, repair and regulate itself. We've just interfered with those systems, which is why we have so much disease. So doing that, you can actually activate your DNA repair systems. One of the ways is by activating sirtuins, for example. with NAD or NR, NMN. And I go through all that in the book. What's the next hallmark? Telomere shortening. Telomeres are these little caps at the end of our chromosomes that prevent the chromosomes from unraveling and they have to be kind of opened up when we replicate and then they close back up. Well, they kind of shorten as we age and then eventually become too short and our cells can't replicate and they die through this process called apoptosis, which is good, or they become zombie cells, which is another hallmark of aging we'll talk about, which then just run around spewing inflammation everywhere in the body. And so, this problem is an issue for many people as they're telomere short and your life shortens. But what causes them to shorten is our toxic processed diet, sugar, environmental toxins, not exercising, stress, and the shorter your telomeres are, the shorter your life. So, the beautiful thing is we know from the work of Elizabeth Blackburn and others is showing the Nobel Prize for this, that we can actually increase the length of our telomeres even as we get older by changing our lifestyle, by avoiding toxins, by doing various kinds of things like meditation, even certain supplements can, can actually extend the length of your telomeres. So there's a lot of good things you can do about your telomeres. The next Hallmark is damaged proteins. You know, proteins regulate everything in our body. There's thousands, thousands, thousands of proteins. I mean, the whole purpose of your DNA is just to code for proteins. And these proteins regulate everything. Your organs, your tissues, your cells are all made up of proteins. All the messenger molecules in your body, like hormones, peptides, immune molecules, neurotransmitters, they're made up of proteins. And they're basically the information superhighway facilitating trillions of chemical reactions every second in your body. Now, what happens over time is sometimes these proteins can get damaged. and then the messages are kind of, you know, staticky or they don't really properly do the things they're supposed to do. David Sinclair talks about aging as an information problem. It's. It's. It's the information theory of aging. And so we end up with these damaged proteins. They don't really work properly, and they become misshapen. And proteins are basically strings of amino acids that are 20 or more, and then they're folded in a certain three-dimensional structure, and then they bind to receptors and they do all kinds of things. So when funky and misshapen or damaged, they don't work properly. So how do we fix these damaged proteins? Well, there's a lot of ways. My favorite way is sauna. It actually is great because it stimulates something called heat shock proteins, which repair and refold some of these damaged proteins. Also autophagy, which is stimulated by inhibiting mTOR through time restricted eating or drugs like rapamycin or other phytochemicals, basically stimulates the process of self-cleaning repair where it digests these damaged proteins that, like a Pac-Man, it gobbles them up and digests them, and then it breaks them down. It kind of gets the old Parts, like, you know, taking it on an old barn and making a house out of it. You got the old wood, but you're gonna make a new house. It's like recycling those things. So basically, we need to prevent this sort of constant flow of food, right? So we need, like, at least a break from eating overnight from 12 to 14 hours. We need to get rid of all the starch and processed sugar in our diet and processed foods. and we need to actually stimulate autophagy. And there's many ways to do this. There are calorie restriction or autophagy generating phytochemicals that we can consume. And I talked about those in the book. Also periods of like fasting overnight that we talked about, all that can really help. And, and so there's ways to fix these proteins. The next Hallmark is the epigenetic damage and epigenetics you might have heard about. But basically, you know, think of your genes as a fixed set of instructions, right? It's like a piano keys. You've got 88 piano keys. You can't change them. They just what they are. But think of all the different things you can do in a piano. You can make jazz, rock, rag, reggae, ragtime, classical music. Right. So the epigenome is like the piano player. It means above. Epi means above your genome, and it regulates this sort of. genes in which genes get turned on or off, the disease genes or the health genes, the longevity genes or the early death genes. And so you can really regulate your epigenome. In fact, the measurement of biological age. And in the book, I talk about how, you know, I'm 63, but my biological age is 43 because I've learned how to regulate my epigenome. And this is how they test for this. They test for your epigenetic health. through something called DNA methylation. And that's beautiful because we can modify it and be changing our diet, exercise, stress, or supplements, our microbiome, environmental toxin exposure, sleep, all these things influence our epigenome and we can regulate them. So the key is to regulate our epigenome using all these strategies which are available to us at often very low cost. and I do talk about them in great deal in the book. So periods of fasting, getting rid of processed food and sugar, eating nutrient dense foods, stress management, exercise, mindfulness, getting rid of toxins, all that really helps. So the good news is we can actually regulate our epigenome and let's do a lot of the things that are involved in, for example, the other hallmarks like the deregulated nutrient sensing. If we fix that, the epigenetics gets better. So that's really good news and we can track our results over time. In fact, some studies have shown that just in eight weeks of changing your diet, doing a very kind of intensive anti-inflammatory diet, a la functional medicine, and a few other lifestyle factors, we can reverse our biological age by three years in eight weeks, which is pretty impressive. So it's good news. The next Hallmark is about what we call zombie cells or senescent cells. These are aging cells. that when cells are supposed to be dying and we have a process for cells dying called apoptosis, where they kind of explode and we recycle the parts, that doesn't happen all the time. And the cells can become zombie cells and they just run around creating more problems. And they create more inflammation, they infect other cells, not quite infect, but they spread their zombieness to other cells. And so pretty soon you get a body full of these aging senescent cells. and the programmed cell death doesn't happen. So that's bad. And the reason is bad is because these senescent cells secrete something called cytokines, these inflammatory compounds that damage nearby cells, that damage tissues, that cause all the age-related disease, and it's really bad news. So how do you regulate and get rid of zombie cells? Well, overnight fast is great. We talked about 12-14 hour fast to inhibit mTOR, for autophagy, things that activate Sirt1, that Sirtuin gene, like, for example, NAD can help this. Exercise is great in fighting zombie cells, working out with weights can really, really help. Also some cool things, for example, like fisetin, which is a derivative from strawberries. It's a phytochemical in strawberries can kill zombie cells. So can hyperbaric oxygen therapy, which is where you go into oxygen tanks. There's a lot of the stuff I talk about on how we deal this in the book. The next is depleted energy, our mitochondria, which is the basic unit of producing energy in the body. It takes food and oxygen and burns them inside your cells and little metabolic engine. And it literally is found everywhere in every cell. And there's thousands to tens of thousands of these in some cells. So these are the powerhouse of the cell. and when, when we do all these bad things, whether it's eat badly or don't exercise or have toxin exposures or microbiome's a mess, we end up damaging our mitochondria and we lose energy, we lose function, we lose muscle. So we have to actually keep our mitochondria healthy. So what do you do to keep your mitochondria healthy? Well, get rid of starch and sugar, which are deadly for them. Eat a lot of phytochemically rich foods with colors and, and, and, and, and, and these many beneficial phytochemicals, eat lots of good fats like olive oil, avocados, Omega-3s and, and the right kinds of vitamins and minerals that regulate these pathways. So, also do time-restricted eating. Light plays a big role, like red light therapy can be very effective. Getting off a blue light at night, super important. Exercise, I can't emphasize that enough, but strength training and cardiovascular training through interval training can be super helpful. I did, for example, an interval training set this morning which was 20 minutes super high intensity on my Peloton bike, and then I did string training with bands for 30 minutes. And that was my morning. And then I, of course, I had hormesis, which was a cold and hot, a hot, I mean, a sauna and then a cold bath. So I, I kind of try to get that in every day. Certain supplements can be very helpful, like CoQ10 and carnitine and lipoic acid and acetyl cysteine, the B vitamins. There's a whole host of these we talk about in the book. But, but you can use, usually help your mitochondria a lot through all these lifestyle practices, plus supplements. The next Hallmark is the gut. and I talk a lot about this. Poor gut health is so common. The seed of our health is our gut. Hippocrates talked about this a long time ago, saying all diseases begin in the gut. He was the father of modern medicine, well, not modern medicine, but he was like a thousand years ago. But he had a lot of things right. Food is medicine was attributed to him, although who knows. And with the advances in science and medicine we have today, we really know that this is true. So many of our metabolic and chronic diseases come from our unhealthy microbiome. and it just drives everything else. It can drive insulin resistance, it can drive mitochondrial dysfunction, it can drive zombie cell production. I mean, just having an unhealthy microbiome is a bad idea. So we want to make sure we keep our gut healthy and we get our digestion working right. And I've written a lot about this in the book. I do talk about how do we fix our guts, how do we optimize our microbiome, how do we heal a leaky gut, which is basically so common where most of us don't even know we have it, but basically proteins and from food and bacterial toxins leak across our digestive tract and cause inflammation throughout the body. And that, that inflammation is, is one of the Hallmarks we're going to come talk about in a sec, which is also driving so much of the problems of Aging. And we call this inflammaging. But inflammaging is really a Downstream result of other things like poor nutrient intake or the wrong nutrients, toxins, microbiome changes. Those are. So inflammation sort of Downstreamed everything else. But it is a huge factor in aging. So, kind of get rid of the things that tend to cause gut issues, whether too much sugar, gluten, dairy, alcohol, things that help heal your gut. I created something called Gut Food, like a multivitamin for your gut, which is polyphenols, prebiotics and probiotics, really important. So, I would encourage you to check that out and keep your gut healthy. And, by the way, all this is just a super high level survey. I just want to give you a flavor of what's in the book. A lot of this is just very practically laid out in the book so you can follow it and fix the problems and actually heal some of these things. The second to last hallmark, hallmark nine, is stem cell exhaustion. Now we all heard about stem cells. They help us repair tissues. We need them to kind of regenerate and rejuvenate, but often they get pooped out as we get older. So they secrete healing factors, growth factors, repair factors, and it's critical you know, we need these. When you cut your skin, why does your skin heal? Because it recruits stem cells, makes new skin, right? If your bone breaks, what happens? You make new bone. So that's really what the body does. And it's brilliant. But it doesn't happen so well as we get older. We get our skin doesn't heal as well. If you cut a little kid, they're healed in a couple of days. If you cut some old person, it's going to take them a long time. So that's, that's the difference. So we, we get our pooped out stem cells, and, and they're everywhere. They're in our, every cell, in our, in our fat tissue, in our in our, in our blood tissue and so forth. So what's causing stem cell exhaustion? All the things we talked about, diet, poor diet, lack of exercise, stress, poor sleep, toxins, allergens, microbes, all the things we have control over. So what's really cool is now we can do things to help rejuvenate our stem cells through regenerative medicine, through stem cell therapies and plasma exchange and exosomes and a lot of things we can do that are really kind of exciting, even taking stem cells, although that's not in the reach of most people, it will be coming down in price. Last Hallmark is inflammaging. And this is the final sort of common pathway that affects aging and it's caused by all the other Hallmarks, too. So it's all one big mishmash and network of dysfunctions. And I, you know, I joke as a functional medicine doctor, I call myself an inflammologist because I try to figure causing it, not just to shut off the inflammation with some drug like steroids or like a, an anti-inflammatory drug like Advil or aspirin, but to find out what's really causing the inflammation. And so what is the driver of most inflammation? It's our diet. It's our pro-inflammatory diet. And one in particular, I would say starch and sugar, ultra processed foods, refined oils, all the additives, chemicals. just terrible. Also, we very low fiber, which affects our microbiome. We were depleted in nutrients, which regulate inflammation, like vitamins and minerals, very, very low phytochemicals in our diet, which are full of anti-inflammatories like green tea, curcumin, all the colorful phytochemicals in our food. I talk about them a lot in the book. And then the microbiome is so affected by our diet and stress and toxins, and that also leads to even more inflammation. so since about 60 to 70% of our immune system is in our gut, it's a huge, it's a huge factor. And then of course you add to that, that load of toxic chemicals in our food, water, air and the cleaning products, personal care products, heavy metals and fish and, you know, it's just everywhere. Lead it, paint, pollution, cold burning plants, arsenic. I mean, you know, it's just a perfect storm for inflammation. Even psychological stress, emotional stress. relational stress, lack of sleep, overworking also drives inflammation. So the question is how do we stop inflammation? Well, we have to deal with the causes and that's what we just talked about. But it's very possible to radically change your immune system and inflammation by cleaning up your diet, by fixing your gut, by lowering your toxic load, by learning how to get enough sleep and dealing with stress reduction. All that stuff will help to reduce inflammation. If you love that last video, you're going Love the next one. Check it out here. Equality, lots of fruits and vegetables, lots of nuts and seeds, good quality fats, no processed food, sugar and starch are not so great for you. You know, really simple principles that we can all agree on. And the whole idea.