The 10 Pillars To LONGEVITY & How To Hack Them To REVERSE AGING | Dr. Mark Hyman

It's important to understand why we age. And once you understand that, you're more motivated to go, oh, geez, if I do this, it's going to 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. Let's get into these 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 we're 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 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 to 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, these are 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 there are often themes you might have heard about in functional medicine, like inflammation, the microbiome, and mitochondria, and there's more, right? And 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 gonna 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 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 also think about it as disrupted hormonal and nutrient signaling. And essentially 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, 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 but I didn't realize it was so connected to these aging pathways. So 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 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 all 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. It's ultra processed food and sugar and starch. It's really, really bad for us. I don't know how to say it any other way. I've written many books about this and 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, and for example, when you're not eating, will clean up and recycle things. And 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 wanna 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, you know, 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 SIRT1. Now, AMPK is a pathway you know, adenosine monophosphate kinase is potentially 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, AMPK. So I would say I'm not a big fan of yet, maybe I will be, I'm open to changing my mind. But based on the data, I think lifestyle is a far better regulator of AMPK 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 as I talk about 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 hormone, humus, therapies, we're going to talk about hermesis in, 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 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, you know, their DNA is required to create all the things our bodies do, and it's basically the blueprint in each cell. 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 in the copy machine. And then your DNA blueprint can be produced with these glitches. Well, what do you do to address that? First, you want to 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, you know, this problem is an issue for many people as they're telomere shortened, 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, the shorter your life. So, the beautiful thing is we know from the work of Elizabeth Blackburn and others, she won 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 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. 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 that 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 they're 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 and 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 can 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 talk about those in the book. Also periods of like fasting overnight that we talked about, all that can really help. 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. It's like a piano keys. You've got 88 piano keys. You can't change them. They're just what they are. But think of all the different things you can do on a piano. You can make jazz, rock, reggae, ragtime, classical music. The epigenome is like the piano player. It means above. Epigenome 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, genes for 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, supplements, 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 through 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 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 SIRT2 and gene like, for example, NAD can help this. Exercise is great in fighting zombie cells, working out with with the weights can really, really help. Also some cool things, for example, like physeter, 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 in an oxygen tank. So there's a lot of the stuff I talk about on how we deal this in the book. The next is depleted energy, you know, 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. There's thousands to tens of thousands of these in some cells. So these are the powerhouse of the cell. And 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 these many beneficial phytochemicals. Eat lots of good fats like olive oil, avocados, Omega-3s, 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 a strength 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 you can 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 seat 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, 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. 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 it's 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 gonna 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 dysfunctions. And I, you know, I joke as a functional medicine doctor, I call myself an inflammologist because I try to figure out what's 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 can add to that, that load of toxic chemicals and our food, water, air, and the cleaning products, personal care products, heavy metals and fish, and, you know, it's just everywhere. Let it paint pollution, coal 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. One of the benefits of eating sugar is that it provides fuel to your brain. Your brain has to have glucose, right? I was trained that that's true in medical school, except it's false. In fact, your body will make whatever sugar you need. There are essential amino acids, there's essential fatty acids.