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RHR: Unlocking the Keys to Longevity by Understanding the Root Causes of Aging, with Mark Hyman


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Dr. Mark Hyman joins Chris on this episode of Revolution Health Radio to discuss his new book, Young Forever. He explores what happens as we age, how food, exercise, and movement play a role in healthy aging, why your mental health, stress, social connection, community, and purpose is so important when it comes to longevity, and what steps you can take to increase your longevity and health span.

In this episode, we discuss:

  • The difference between normal aging and abnormal aging
  • What happens as we age and what you can do to address these hallmarks of aging
  • How food plays a role in healthy aging
  • The role of exercise and movement in longevity
  • Why connection, community, and purpose are so important when it comes to longevity
  • The most exciting and promising new therapies with potential to stop or reverse aging
  • The top things you can do to increase your longevity and health span

Show notes:

Hey, everybody, Chris Kresser here. Welcome to another episode of Revolution Health Radio. Aging in the industrialized world is not a pretty picture for most people. It’s generally a gradual, or sometimes rapid, decline. Increased prevalence of illness and chronic disease, becoming less independent, less autonomous, and often spending the remaining years in either a memory care facility or in a type of situation that I think we would all agree is not ideal. But does it have to be that way? Certainly, death, as far as we know, is inevitable at some point, and chronological aging continues. We were born when we were born, and we get older. As far as we know, there’s no stopping that, at least in the future that we can imagine right now. But is there a way that we can slow the process of aging? Or put in a different way, can we slow or even reverse what we might call abnormal aging? Which is the aging that we have come to accept as normal, where we gradually lose function, develop more disease and dysfunction, and generally end up in a place that none of us would like to be. That’s the topic of this podcast.

I’m really excited to welcome Dr. Mark Hyman as my guest. He generally needs no introduction if you’re at all familiar with the Functional and integrative medicine space. Mark’s been a guest on the show three or four times in the past. He’s a dear friend and a mentor and a colleague, and he has a new book called Young Forever, where he explores these questions. What are the hallmarks of aging? What drives abnormal aging? Can we address those hallmarks? What are the mechanisms, as far as we understand them now, that explain aging? How do things like exercise and physical activity, stress, social connection, [and] food affect the aging process? And most importantly, what can we do as individuals to identify and address those hallmarks of aging and slow or even reverse the process of abnormal aging? There’s some really interesting research that we’re going to talk about around that. A lot of these conversations about anti-aging end up focusing on really high-tech or innovative new therapies, new drugs, or interventions like stem cells or exposomes or things like that. We’re going to touch on those, because I think they will impact our lives at some point. But this conversation is much more focused on the simple things that all of us can do to slow aging. And Mark and I agree that those factors are far more important than these higher-tech, new interventions that may have some impact on our lives later on. Even if and when that happens, I would argue, and I think Mark agrees, the basics are still far more important.

This was a really fascinating conversation. I love his new book; I read it cover to cover. That’s pretty rare for me at this point because I get so many health books sent to me. But this one really was worth reading and worth talking to Mark about. I hope you enjoy the conversation as much as I did. Let’s dive in.

Chris Kresser:  Mark Hyman. Such a pleasure to have you back on the show for number, I think it’s number three or four. I always love our conversations. I’m really excited to dig into this latest book of yours because I’m getting older, at least in terms of chronological age. I actually feel in some ways like I’m getting younger, which is going to be a big topic of our conversation. What does it actually mean to age? I mean, I want to start with the biggest picture stuff and then we can drill down.

Mark Hyman:  Yeah, how geeky do you want to get?

Chris Kresser:  Well, you know me, and you know my audience, so we’re going to do a little bit of both.  I started [from] the beginning [of] your book, and of course, you started with the biggest question. Is aging inevitable? We look around the world at different species of animals, and we see that all animals we know of age and eventually die. Is that inevitable in the future?

Mark Hyman:  I mean, I think death is pretty much, at this point, like taxes, inevitable.

Chris Kresser:  Death and taxes.

Mark Hyman:  Until we come up with some really radical new interventions, I don’t think we can escape death. But there is this concept out there called longevity escape velocity, which is [that] the advances in science will continue so fast that it will keep prolonging your life faster than we actually age. So we can potentially stave off death inevitably. I’m not sure that’s a good idea for many reasons, but I think it’s an interesting question about, “What is our potential lifespan?” You have [Greenland sharks] at 400 years, tortoises [for] maybe hundreds of years, [and] bowhead whales are [at] 200 years. That’s a long time. So, what are the mechanisms of aging? What are we seeing around us in this culture as aging? And how is that actually maybe abnormal aging? The things that we come to understand as a normal consequence of getting older [like] declining function, decrepitude, frailty, some mobility, disease, these are just things that we seem to come to accept as normal parts of getting older. But they’re not necessarily true. There are many people, and I’ve met many of them when I was in the Blue Zones, who are 100 years old and still riding horses and functioning and climbing mountains. And I’m like, “They’re not walking around with a walker.”

Chris Kresser:  Absolutely. Here, where I live in the mountains, I was just skiing this morning with a woman who’s 82 years old and absolutely ripping. Not just getting by, [but] one of the best skiers on the mountain. And she’s out there most days. I think, [and] you mentioned this in the book, we’ve all had the experience in our life of seeing aging happen really differently among different people, right?  Some people look 10 or 15 years older than their age, and other people, like you said, [are] out riding horses in their 90s, or skiing, or surfing, or doing all kinds of cool stuff, starting new businesses, whatever.

Let’s break that down because clearly, there’s something happening there. You talk about this distinction in your book between different types of aging. How do you break that down? There’s chronological aging that happens no matter what, right? The clock [is] ticking and passing. But then, beyond that, there [are] all kinds of variation in how aging actually happens.

Mark Hyman:  Totally. I mean, I’m 63. I can’t change that. I was born in 1959, and that’s just going to be the way it is, and I’m going to get chronologically older unless I go out into space. But biologically, that’s another question. How do we understand the basic design of the human body? How do we understand how to work with it to activate these ancient innate longevity systems? These healing, repair, renewal, regeneration systems that are embedded in us. When we cut our skin, it heals, which is a fricking miracle. We have surgery, [and] our body heals. It isn’t, “Oh, you have to take this drug to heal your skin.” Your body has its own healing systems. And we’ve pretty much done everything in our culture and our way of life and our lifestyle to screw up those healing systems—the way we eat, the lack of exercise, the amount of stress, the sleep deprivation, the environmental toxins, and I could go on and on, are all interrupting our body’s natural, innate wisdom and healing and repair systems.

When we look at what works with us, rather than against us, and we start to add in those things in our life that actually activate these ancient healing systems and take away the things that are interrupting them, we can literally reverse the biological age by reprogramming our biological software. We can reprogram our epigenome, which is a big regulator of aging. We can reprogram our metabolic health, our hormonal health, our nutritional health, and these things are really critical if we’re going to understand how to not only live longer, because it’s not only about just living longer; it’s about living well longer. It’s about healthy aging. It’s about extending your health span. Because [for] the last 20 percent of most people’s life, their health is not good. Your health span maybe is 60 years, and then your life span might be 80 years, but the last 20 years is kind of crap. Why not be able to live a full life and then just die? [That’s] kind of my plan.

Chris Kresser:  Yeah, in your sleep, die, check out. That makes a lot of sense. Spending the last 10 years of your life in a diaper and a wheelchair, where you can’t remember who you are, is not anyone’s idea of a good old age. And yet, that’s pretty common now, at this point. We have this conventional medical system that’s really good at these heroic interventions later in life that keep people alive, but they don’t keep people living, right?

Mark Hyman:  No. That’s true. You asked before how we think differently about our biological and chronological age. Our biological age is our age on the inside, not necessarily our clock age. And we can change that through these mechanisms that influence longevity. I call them the longevity switches. We now understand that there are these fundamental processes that we can influence called the hallmarks of aging. We can understand what goes wrong, and we can create very specific interventions to correct these dysfunctions that underlie all disease.

If we actually cured heart disease and cancer from the face of the planet, we might extend life by five to seven years. If we understood how to optimize these systems that go wrong instead of advancing the hallmarks of aging, we might get 30 or 40 years of life extension, because these things are underlying all disease. We’re doing whack-a-mole medicine, where we’re treating heart disease and diabetes and cancer and dementia. Rather than doing that, we should treat the underlying reasons why these diseases occur. And that’s Functional Medicine.

Chris Kresser:  I was going to say this sounds suspiciously like Functional Medicine, Mark. I don’t know what you’re talking about.

Mark Hyman:  It is, pretty much. But it’s actually the lens that I use for my book because a lot of the longevity books and a lot of the longevity research is focused on these hallmarks, but [on] finding drugs or other things to interrupt them. I think that’s a mistake. I think we have to look at, what are the causes of these hallmarks and how do we work with them?

Chris Kresser:  You and I often agree on a lot of things, and I wasn’t surprised to see that in the book. Because that is my critique of a lot of the anti-aging stuff out there. It’s like, “Take this. Oh, this new drug.” And of course, rapamycin, metformin, these drugs can have a place, for sure. But if you’re doing that on top of all kinds of broken stuff, you’re not going to get great results. You’ve got to fix the basic things first and address the underlying causes. That’s why I think this book is so refreshing, because you acknowledge that those interventions that are more advanced can play a role, and I’d love to chat a little bit about those later in the conversation, but you make it clear that if you’re not doing the basic stuff first, don’t bother with those other things. Get those basics right, and then, later on, the other stuff.

Mark Hyman:  If you’re eating three pounds of sugar a day, it doesn’t matter if you take rapamycin.

Chris Kresser:  How much rapamycin or metformin do you take? Exactly. A really crucial thing that I want people to understand from this conversation is that aging, just normal aging, is what it is. But what you’re talking about here is abnormal aging as a disease. Which is, I think, a really big shift for people to understand. Then abnormal aging is the disease that drives all of the other downstream diseases of aging that we know about—dementia, Alzheimer’s [disease], even early fractures, which are a big cause of death, etc.

So let’s talk about this a little bit because this is, I think, a big paradigm shift for a lot of people to get their head around. We can’t cure death that we know of now, but we can dramatically slow abnormal aging if we look at it as a disease and then look at it from a Functional Medicine perspective, where you’re identifying and addressing the root causes of abnormal aging, which you call the hallmarks of aging. Maybe let’s talk about the top three, or a few of those, so people have a sense of what those are.

Mark Hyman:  I think you’re so right. We can actually not only slow aging, [but] we can [also] reverse it. I think that the most exciting data I’ve seen is about interventions that reverse biological age as measured by looking at your biological clock, which is measured by looking at DNA methylation patterns on your genes, which control which genes are expressed or not and which are modifiable. We can’t change which genes we have, but we can change which genes are turned on or off and how they’re expressed. And that is influenced by lifestyle and many other things we do in Functional Medicine. I’ve seen this in Kara Fitzgerald’s study where they did a very aggressive dietary intervention based on Functional Medicine and a few lifestyle things. In eight weeks, they reversed biological age by three years, which is just stunning, right?

Chris Kresser:  Incredible. We’re not talking about three years of hard work here.

Mark Hyman:  Eight weeks. Eight weeks. Your body is amazing, and I’ve seen people reverse all sorts of diseases in just a few months by putting the right information in the body. The hallmarks, I think, are many, and they’re all related. But I think one of the overarching ones is this phenomenon [called] deregulated nutrient sensing. It’s one that, if your nutrition isn’t right, can screw up all the other ones. If your nutrition is crappy, you get more DNA damage, more epigenetic changes, more mitochondrial dysfunction, more damage to your proteins, more inflammation, and I could go on and on. Telomeres shorten because of poor diet. On the other hand, if you understand the way in which [what] I call these longevity switches can be regulated by diet, by when you eat, what you eat, [and] how you eat, then you can start to be a master of your biology. There [are] four main pathways or longevity switches or mechanisms that are regulating our aging process that have to do with the food we’re eating, and we have huge influence over those by the quality of our diet, by the timing of our diet, and many other factors. So I’ll just briefly talk about them.

There [are] two that are detecting an abundance or excess of nutrients, and there [are] two that detect not enough or scarcity. And these are all ancient systems that are designed to keep us alive, to keep us living longer, to turn off inflammation, to clean up old cells and repair damage, to help us increase our antioxidant systems, to improve our mitochondria, and they’re all really beautifully designed. We just do everything we can to screw them up. The first is the insulin signaling pathway. This is really a big one, and it’s probably among the most important of the problems that we see with aging, which is too much food that causes our insulin [and] our blood sugar to spike. Carbs, and not necessarily all carbs because obviously, broccoli is a carb, but starch and sugar. Basically, flour and sugar in any form is driving excess stimulation of insulin, which causes overgrowth of many things including cancer, belly fat, [and] inflammation. It slows your metabolism [and] causes dementia, heart disease, [and] diabetes. One of the keystone parts of understanding longevity is dealing with this sugar and flour problem in our society, which is the main source of our calories, unfortunately. That’s a big one. It’s not that you don’t need to stimulate insulin occasionally to help with your blood sugar regulation and everything else, but it’s the overstimulation of this.

The second one is called [mammalian target of rapamycin] (mTOR). This is one that’s really controversial in many ways. It’s so misunderstood because many in the longevity space are saying, “Oh, mTOR, when it’s overstimulated, prevents our bodies from doing cellular cleanup called autophagy. So the key to longevity is to mimic calorie restriction and not stimulate mTOR, and be able to induce this process of repair and cleaning up called autophagy, which is really important.” But what they miss is that we also need to stimulate it at the right times to build muscle and synthesize protein. This is such a key function in the body that if we don’t build and maintain and increase our muscle health and size and function as we age, we become old very fast. Muscle is the currency of longevity. So, yes, we need to give mTOR a break and inhibit mTOR so we can stimulate this cleanup process. But we also need to stimulate mTOR to build muscle. So, how do you do that? Well, you can take periods of time during the day or overnight where you’re not eating, which is not something we do in this culture. We eat all night, we eat bedtime snacks, and then we eat first thing in the morning. A 12-hour [or] 14-hour overnight fast means you eat dinner at six and you have breakfast at eight in the morning. That’s a 14-hour fast, okay? That gives your body a chance to repair and do this autophagy process. Then you need protein [in] a fasted state first thing in the morning, usually more than would we think, probably 40 grams to stimulate muscle synthesis and activate mTOR.

It’s like the Goldilocks thing. You don’t want to stimulate it all the time, but you want to make sure you stimulate at the right moments in the right time with the right kind of protein. And animal protein has a particular quality to it, which allows mTOR to be turned on.​ The reason it has that is because it has higher levels of an amino acid called leucine, which is a rate limiting amino acid for muscle synthesis. If you have low leucine, let’s say from plant proteins, you have to eat a ton of them or you have to jack them up with added supplemental amino acids, which a lot of these plant proteins do. If you want to see bodybuilders who are vegans, the way they do it is by eating large amounts of processed plant proteins with added amino acids that jack up the ability of the body to synthesize muscle. So you can do it if you’re a vegan, but you have to eat a lot of processed food.

Chris Kresser:  Yeah, I want to linger on that for a second. Because for a while, I feel like the tide has turned on this a bit. Everyone interested in longevity was starving themselves because there were studies showing calorie restriction was beneficial. In my view, you just end up being cold and miserable for most of your life. You might live a few years longer. But I think mTOR holds the key to the balance.

Mark Hyman:  You’ll have low libido, you’ll be skinny, and [have] muscle wasting.

Chris Kresser:  Yeah, and you look terrible. I’ve met some of those people, and they look horrible. I’m like, “Why do you even want to extend your life if you look like that and feel like that?” So I’m glad you brought this [up] because I think mTOR is one of the reasons why that approach is unlikely to work for humans.

Mark Hyman:  Yeah, and I think it’s interesting that a lot of longevity scientists, [people] who’ve spent their life studying longevity, are promoting a vegan diet. [It’s] just kind of shocking to me because it’s very reductionist, and it doesn’t understand the other part of longevity, which is muscle. And that’s key. So I think that’s an important piece.

The other thing is these two other pathways that detect not enough nutrients, sirtuins and NPK. They’re involved in mitochondrial health, DNA repair, inflammation regulation, and many, many other factors that help with longevity. What’s really interesting is that sugar also screws these things up, if you have too much sugar and processed food. Metformin works through acting on the NPK pathway, which is important, but it’s a really, I think, lame attempt to try to extend longevity by regulating insulin resistance through a drug rather than the best way, which is through diet and exercise. I think it’s a little misguided, and we’re going to be seeing more data. I’m not prescribing metformin for longevity at this point. I’m kind of waiting. The [Targeting Aging with Metformin] (TAME) Trial is coming out. It’s a big, randomized control trial. I think it’ll show some benefit, but compared to what? Compared to eating a very healthy, low glycemic diet and exercise? I don’t think it’s going to work as well.

Chris Kresser:  I don’t think so either.

Mark Hyman:  And then sirtuins, I think, are important. People are talking about how to activate sirtuins. Resveratrol was a big craze for a while, but you had to take a lot to do it, and that may not be the best way. But [nicotinamide mononucleotide] (NMN) and [nicotinamide adenine dinucleotide] (NAD) and [nicotinamide riboside] (NR) are natural compounds that your body uses in energy metabolism. When your nutrient levels are low, NAD increases and increases the stimulation of sirtuins, which will (inaudible 21:16) about all the good things you want to do like DNA repair and lowering inflammation. So I think there’s exciting research on NMN, NR, and NAD. There’s some controversy about it related to cancer, but I think this is in animal models, and it’s very limited. I don’t think it’s a big factor.

Chris Kresser:  Yeah, this is fascinating. I love talking about these mechanisms, and you may not have even seen this because, literally, this study was published yesterday, or at least I saw the report on it [then]. It’s from Jonas Salk Institute, and the researchers found that when telomeres shorten, they communicate to the mitochondria, the energy powerhouse of the cell, and basically tell that cell it’s time to wrap things up and initiate a process of apoptosis, cell death, and inflammation inside of the cell as a protective mechanism to destroy the cell before it can become cancerous. So, this is another layer of understanding of how the aging process actually works, because it’s abnormal aging shortening those telomeres and then sending that self-destruct signal to the mitochondria.

Mark Hyman:  Yeah, it’s true. I think what’s exciting is that we now know, for example, it’s not a one-way street. You can increase telomere length. Hyperbaric oxygen therapy increases telomere length. Exercise, a multivitamin, meditation, getting enough sleep, [and] eating a whole-foods diet all increase telomere length. Biological aging is not a one-way street. I did my biological age, and [chronologically], I’m 63, but biologically, I’m 43. I mean, I’m trying to get to 25. We’ll see how it goes.

Chris Kresser:  You’re going to be living in a hyperbaric oxygen chamber.

Mark Hyman:  I wish. Honestly, I wish I could. I’m working on building a place in Costa Rica where I have all the toys that I want.

Chris Kresser:  All the goodies.

Mark Hyman:  Yeah, all the goodies.

Chris Kresser:  Yeah, and sauna, infrared light. Here’s the good news, because I think sometimes people hear these conversations about longevity and they think, “Well, I don’t have access to hyperbaric oxygen or all these fancy things. They’re too expensive.” What you just said is all the basics—stress reduction, meditation, eating a whole-foods diet, [and] we’re going to talk about social connection here in a moment because that one is huge, and I know you really focus a lot on that in your book and your life. It’s the basics that are so important. I find myself constantly bringing people back to that because I think we have a tendency to want to find the answer in a pill, or in some super teched-out, fancy intervention. But it’s the basics that make the biggest difference. When I had David Sinclair on the podcast, he agreed with me. I think most longevity researchers who are really paying attention to this will agree with that.

Mark Hyman:  It’s so true. I wrote a book years ago with a pastor, Rick Warren, and Daniel Amen, and it was called The Daniel Plan about Daniel from the Bible, who resisted the king’s temptation of rich food and was healthier for it. We talked about five things that are the foundation of health and longevity—faith, and that doesn’t have to be religious faith, but it can be meaning and purpose. Your kind of ikigai, which I talk about in the book, which is your reason for being. The second is food, [and] the third is fitness. We talk about the five Fs, right? Faith, food, fitness, focus, which is your mindset and your beliefs, and the last one is friends and community. And I would say friend power is more powerful than willpower, and community is medicine. It’s really so true. We looked at the risk factor[s] of social isolation and loneliness; it’s just a huge problem in our society. It’s a disconnection and social isolation and division. When you go to the Blue Zones, it’s all about community. It’s all about enjoying each other. It’s laughter and play and hanging out. I was traveling in Sardinia, and we were driving and went to this beautiful town way up in the mountains, and we’re meeting all the old people, and then we were leaving and driving out of the town, and this guy stops in front of us, a guy named Carmen, and he was probably 86 years old. He had a little Fiat Panda and he pulled it over, kind of blocked the road, sat on this stone wall, and he waved over to us. I said to my guy at this thing, “What’s going on here?” [And he said,] “Oh, he just wants to talk.” Like, who does that?

Chris Kresser:  Yeah, and you’re like, “I’m going to get robbed here.” In the [United States], it’s a totally different thing.

Mark Hyman:  So we sat on this stone wall for like an hour and chatted about his life and his whole story. It was quite amazing. He says, “Come, come,” and we went and saw his farm that he had through his family for hundreds of years and all the fig trees, and he had all these animals and sheep and this vegetable garden he was growing. And he did the whole thing himself, and he was like 86 years old. And I’m like, “Wow.” I mean, growing a little garden is a big project. But this was huge.

Chris Kresser:  That’s a lot of work.

Mark Hyman: At one point, he ran up this hillside to go after a sheep, and I tried to go after him and I had trouble keeping up with him. And he was like 86 years old. In Sardinia, he’s just, like, middle aged.

Chris Kresser:  I love that.

Mark Hyman:  So the power of community is so important, and we need to learn how to cultivate that. I’ve found that in my own life, you know, you get busy, you get focused on [your] career, but making a commitment and time to develop deep friendships and connections is super important. During [the] COVID[-19 pandemic], I called a lot of my old guy friends and I said, “Hey, let’s start a men’s group and just meet every week or so.” And they were like, “Oh yeah, let’s meet every week for two hours.” So we Zoom in every week for two hours. And we’re all over the place, it’s not like we do it in person, but it’s a beautiful thing to be in a place where you can be seen and known and have this human connection. That is one of the most important ingredients for longevity.

Chris Kresser:  Absolutely. My podcast listeners probably get tired of me talking about this study. I know you know the one I’m talking about. It showed that lack of social connections and social isolation is a greater predictor of early death than smoking 15 cigarettes a day. I think that’s such a shocking statistic for people to hear. Something that’s, relatively in their mind, maybe intangible. It’s not connected to what they’re eating, or even smoking cigarettes could have that dramatic of an impact on our life span.

Mark Hyman:  It’s so true. It’s so true. Yeah.

Chris Kresser:  One of the things that strikes me about Sardinia and some of those other places is how it’s almost impossible to be disconnected living in that kind of environment. It’s more of a challenge, I think, for people in our culture, because we live in these isolated nuclear family living situations, not multigenerational homes like in Sardinia. A lot of people end up feeling cut off from their community. A lot of people don’t even know their neighbors. You could live somewhere for 15 years and not even talk to your neighbors more than a handful of times during that period. But I see there’s a big movement, as you know. You mentioned Costa Rica. There [are] eco villages springing up all over Costa Rica and Mexico. There’s even new housing developments [in Florida] that have schools and parks and grocery stores and everything built into the community. I’m glad to see that it seems like there’s a bit of a renaissance or a movement back toward that kind of configuration of living. Because that’s how human beings evolved, right?

Mark Hyman:  Totally, totally. We’re tribal. [If] you put a human out there in the world by himself or herself, it’s not going to be a pretty picture. It’s harder to survive on your own. We need community and tribe. That’s how we get things done, that’s how we make progress, [and] it’s how we grow. Think about the interdependence of all of us as human beings. We’re not these islands that can live alone without any support from the outside world. It’s so important for us to build a community and connection wherever we are.

By addressing the root causes of aging, we can not only increase our health span and live longer but prevent and reverse the maladies of aging—including heart disease, cancer, diabetes, and dementia. #chriskresser #aging #longevity

Chris Kresser:  Let’s talk a little bit about exercise, and even expand that to physical activity and movement. I’ve always been struck by the fact that if you look at any studies on dementia, Alzheimer’s disease, cognitive decline, neurological disease, etc., I would say hands down, the most powerful intervention that we know of, at least from the scientific literature, along with diet is movement and physical activity.

Mark Hyman:  Chris, it was so fascinating to me as I was writing the book to look at exercise through the lens of longevity and through the lens of the hallmarks of aging. We can look at it as increasing fitness, increasing muscle mass, and helping your mitochondria. There’s a lot of things we already know about exercise and health and the benefits, and your blood sugar, and so forth. But when I started to really dig into the science, it’s so fascinating to me how exercise is almost like this magic potion that can optimize all these functional systems in our body and reverse the hallmarks of aging. It reduces inflammation, it improves your mitochondria, it helps your protein function, it helps regulate insulin signaling and mTOR and NPK and sirtuins, and [it] helps improve your epigenome and lengthen your telomeres. So it’s like, “Wow, wait a minute. Exercise isn’t just this abstract thing that makes you live longer and feel better.” We now understand the mechanisms through which it works. And that’s, to me, really exciting.

So to me, other than food, exercise, particularly as you get older, becomes more and more important. And the right kind of exercise. Yes, we need fitness and cardiovascular fitness. VO2 Max is the measurement of your fitness level. It’s how much oxygen you consume per minute, which is related to how many calories you can burn. It’s a measurement of your mitochondria and your fitness level, [which is] very important. But also, strength training and muscle mass. This is where I think a lot of people go wrong with longevity. They miss the importance of resistance exercising, and the importance of protein along with it, to build muscle and make healthy muscle. Because you can have unhealthy muscle, which is marbled like ribeye steak, or you can have a filet mignon, which is what we really want. The reality is that muscle is the currency of aging, and if you lose muscle, which we all do if we don’t do anything. When I was 50, I couldn’t do 10 push-ups. Now I can do 80 or 90 push-ups without stopping. That’s a big change. I look at myself when I was 50, and I’m way more in shape now at 63 because I’ve understood what to do and how to do it. And it’s not like I spent hours and hours a day exercising, although I’d love to. I’m too busy. But with very limited amounts [of] the right types [of exercises], you can see really tremendous changes in your body.

So I think it’s important for us to commit to some type of resistance training as we get older. And also flexibility—yoga, stretching, whatever you like to do. Because when you become stiff and rigid, that’s not a good thing with aging. The reason people end up in nursing homes is they can’t cut their toenails or tie their shoes.

Chris Kresser:  Absolutely. Or as the saying goes in medicine, break your hip, die of pneumonia. Premature fractures are one of the leading causes of death in the elderly, and that often happens because of not enough muscle, not enough flexibility, etc.

Mark Hyman:  Totally.

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Chris Kresser:  You and I both have practices where we treat a lot of people with complex chronic illness, and I would say the same thing to my patients with chronic illnesses. Even though it was counterintuitive for them, like “What? I’m sick and you’re telling me I need to go lift weights and build muscle?” But building muscle is really important for anyone who’s struggling with any kind of chronic health challenge for the same reason that it’s important as we age—muscle is the source of metabolic health and vitality.

Mark Hyman:  Yeah, yeah. That’s the thing people don’t realize. Your muscle is not just moving your bones and skeleton around. It’s an incredible metabolic organ. If you have marbled fat as you get older, which can happen, you can be the same weight at 65 than you were 25 but literally be twice as fat. And when that happens, you get this thing called sarcopenia, which is the death knell. That means your muscle is not able to regulate your blood sugar very well, your mitochondria are not functioning well, you have more inflammation, you have lower testosterone, you have lower growth hormone, you have higher cortisol, [and] you have more oxidative stress. Pretty much everything you don’t want as you age happens as you lose muscle.

I always hated strength training. I didn’t like gyms. They were smelly and [had] all these muscle heads, and I just didn’t like it. No offense to the muscle heads, but I’m a tall, skinny guy, and I’m like, “Uh …” But I’ve used bands and resistance training, and I can do it at home. I can use body weight. And I’ve found it also helps me just feel better and move better and do more stuff. It’s amazing to see what my body can do at 63 years old. When most people my age are on their way down, I feel like I keep getting better. I get better at tennis, I get better at my fitness, I get stronger, [and] I get more muscles. I’m like, “Wow, this is really amazing. This shit works.”

Chris Kresser:  Yeah, it’s incredible. I’m a little younger than you, but at 48, I feel more fit than I have been in my adult life. All of my activities, it’s the same. And I just want to emphasize [what] you said before—we’re not talking about having to be in the gym for two hours a day. In fact, I never go to the gym. I got some equipment [and] I have it in my garage, so I just go out there. And there [are] so many new ways you can train that weren’t around when we were younger. There’s bands, like you said, there’s the X3 system, which is also resistance band, there’s kettlebell training, there’s all kinds of functional bodybuilding, TRX, all this. You don’t have to get bored. You can bring TRX straps in your bag when you travel and hang them on the back of your hotel room door and get a really good workout.

Mark Hyman:  I use bands. I use Tom Brady’s program. Tom Brady [is a] legendary football player, but he never lifted weights. He used resistance bands. He (inaudible 35:18) pliability, flexibility, and resistance bands. It’s just amazing how great they are. You don’t injure yourself, [and] you can do it anywhere. I can do it literally anywhere I am. I bring them to the hotel room or when I’m in somebody’s house, and I just [strap] it to a bed. If I need to, I can hook it onto a railing or to a tree or anything. It’s quite amazing.

Chris Kresser:  And you don’t even need that. I’ve been in hotel rooms where I’m doing dips with my hands on the countertop and my feet propped up on a chair. You can do push-ups anywhere. All it really requires is a commitment to do it. And we’re talking about [that] you can get significant results in a half-hour a day or less, for sure, and really extend your health span.

Okay, we’ve talked a lot about the basics, which I really wanted to focus on, because it is one of my pet peeves with these aging discussions where people go right to the fancy [interventions like] stem cells. Which largely is stuff that’s inaccessible to like 99.9 percent of people who are listening to the podcast. However, there are some really exciting new discoveries that have happened in the field of anti-aging research, which you cover in the book. Let’s start with stem cells. The Japanese researcher who has [a] very exciting discovery. What can we reasonably look forward to in the next, let’s say, 10 to 20 years, in terms of new developments that might help with this?

Mark Hyman:  Well, there’s some really exciting things that are coming down the pike. But before we get to those, I want to talk about, in addition to basic diet, exercise, sleep, and stress management, another set of activities or things that you can do that are available to almost everybody [and] are incredibly effective in enhancing your health and longevity, have to do with this framework or concept called hormesis, which is basically a stress that doesn’t kill you, that makes you stronger. You can integrate simple hormesis practices that have been proven to optimize your health and to work on many of these hallmarks of aging. What is an example of those? Well, fasting is an example because that’s a stress. And that can just be an overnight fast for 14 hours, or it can be [one] day a week, or it can be three days every quarter. There [are] many, many ways to do this. But giving your body the stress of not eating turns on all these longevity pathways. We just talked about exercise, [and] that’s another form of hormesis. You’re pushing your body to do something, and that’s the stress, and that activates the longevity switches.

Then there [are] other ones that are relatively easy to do. Most people have a shower in a bathtub. You can take a really hot bath that increases your body temperature, and that activates heat shock proteins and your innate immune system, and also has many other benefits [of] lowering cortisol and relaxing your muscles if you put in Epsom salt. If you have a sauna, you can use that. That’s been shown in Finland to dramatically reduce your risk of death if you do it four times a week.

Chris Kresser:  Or just go to a gym that has a sauna. You don’t even need to have one yourself.

Mark Hyman:  Yeah, you go to a gym that has a sauna. They have sauna blankets now. They have stuff you can get relatively inexpensively, and that’s such a powerful intervention. Cold therapy is another one. You can take a cold shower for two minutes in the morning. I was staying at a friend’s house who had a cold plunge, and I was in a cold plunge for three minutes this morning, and it was a fantastic way to wake up. It’s better than coffee. It’s a little shocking to the body, but you learn how to get used to it and use your breathing and your breath. [It’s] very powerful in activating brown fat and mitochondria and energy metabolism and increasing dopamine and focused and cognitive health. So, these are simple practices that you can incorporate. There [are] still other ones like hypoxia, which you can put [on] a mask you buy for a few bucks [from] Amazon that restricts your oxygen intake, and you do that for periods during the day that stimulate your mitochondria. There [are] all these practices [that] I talk about in the book.

Chris Kresser:  Or you can move to the mountains and live at 7,000 feet.

Mark Hyman:  There you go. Like you. You got it down.

Chris Kresser:  Yeah, and I love the hormesis discussion because a lot of people don’t realize that’s the way [antioxidants] work, too. They’re actually pro-oxidants. They induce a mild hormetic response, and they upregulate our own endogenous antioxidant defense system.

Mark Hyman:  Yeah, so this is like, I call it phyto-hormesis, which is the plant compounds that can stimulate some of these pathways, and they’re very effective in activating longevity switches. All these things are available to us. There’s some other more advanced hormetic therapies like hyperbaric oxygen and ozone, which are more expensive, that are coming down the road. But I really love some of the research on hyperbaric oxygen as an intervention that can help kill zombie cells, which are one of the hallmarks of aging, these cells that go around spewing out inflammation or lengthen telomeres, more than any other intervention. I think hyperbaric oxygen is going to be a really important intervention. Also, ozone is another one that can be very effective, and that’s not super expensive. Most people can get access to it. You can get a machine; you can do rectal ozone at home. There [are] some issues with that, but ozone therapy can be very powerful.

And then, coming down the pike, there’s stuff that I think is really exciting. Obviously, stem cells, exosomes, peptides, and this other one called plasmapheresis, which I think might turn out to be one of the most important interventions. Essentially, it’s filtering and cleaning your blood. They did experiments with animals where they would hook up the circulation of an old mouse to a young mouse, and then the old mouse would become young and the young mouse would become old. And they’re like, “Well, what’s going on here?” Then they reverse engineered the mechanism by trying to clean the blood of an old mouse without hooking it up to a young mouse. It wasn’t stuff in the young mouse that was making the old mouse young; it was stuff in the old mouse’s blood that was making the old mouse old, if you follow me. They took this technique that’s used in medicine called plasmapheresis, which essentially takes your blood out of one arm, filters it, removes the plasma, which is the soup that all your cells float around in and is full of all these inflammatory compounds and damaged proteins and crappy crap in your blood, and it filters that out. Then it puts your cells back in without the plasma, and that gives you this chance to build new plasma and renew yourself, or you can add albumin. And the studies on animals where they’ve done this does all the same things as this parabiosis, this hooking up these circulation studies.

It’s pretty amazing, and I personally have had some experience with it. I don’t know if you’ve ever tried it, but I did it after I had COVID[-19]. I had terrible arthritis, with my hand blown up and tons of inflammation in my body. I felt like crap. I did plasmapheresis, and the next day, it was gone, just like that. All my symptoms—arthritis, my brain fog, feeling crappy after COVID[-19], it just went away. So I think that this is a very promising therapy, and we’ll see how it goes. Exosomes are another one, which are the active healing components of stem cells that can be manufactured in the lab, can be given in high doses, [and] can activate all these incredibly powerful systems. I had colitis after taking an antibiotic for a bad tooth, and they gave me Clostridium difficile, which is a horrible intestinal infection, and then I got colitis after that. It was really horrible, and I couldn’t get better. I tried all kinds of things. I did ozone, which helped a lot, but then I got it again. I tried IV exosomes, and it went away, just like that. Now I’m perfectly normal. People say colitis is a lifelong thing, an autoimmune disease, [but] I don’t have anything. I’m perfect. I went from being hospitalized, basically, to being very perfect with just some simple intervention. So I’m excited about what’s coming down the pike. There [is] some sci-fi stuff coming down the pike, like 3D printing of organs and epigenetic reprogramming and Yamanaka factors and cool sci-fi stuff, but we’re not quite there. I think we’ll get there though.

Chris Kresser:  Yeah, we’ll get there, and it will become more available to more people. Right now, a lot of the stuff that you mentioned is all out of pocket; it’s expensive, very few people do it, [and] very few people do it well. There are people who are definitely doing it not well. I’ve seen that. So yeah, back to basics. I think it’s fair to say that dialing in your sleep, your stress management, your diet, your physical activity, and then layering on that next level of hormetic factors like cold exposure [and] heat exposure. And again, you don’t have to have a sauna; you can just take a super hot bath. You don’t have to have a cold plunge; you can take a cold shower. If you live in a climate like I do, go lay in the snow outside.

Mark Hyman:  Or put your bathtub full of cold water. That’s what I do.

Chris Kresser:  And eating a wide variety of phytonutrients that have that phyto-hormetic effect, like you mentioned. Slight tangent here, this is why I think the carnivore argument is absurd when they say plants have toxins. I’m like, “Awesome. Yeah. I want those small amounts of toxins because they’re going to help my immune system and hormetic response function better.” All of those things are accessible to most people, as well, and they just take things up a notch. Then and only then, in my way of looking at it, does it make sense to look into those higher-level things. Or if you have a health challenge, like you did, that needs that kind of attention. Otherwise, focusing on the basics is going to yield a much higher return on investment.

Mark Hyman:  So, so much. Yeah, I mean, it’s amazing. An example of a patient I had who was 66, had a body mass index of 43, [was] just massively overweight, [had] diabetes for 10 years, [was] on insulin, [had] heart failure, [and had a] history of multiple stents, angina, [and] high blood pressure. [Her] kidneys were failing, [her] liver was failing, [she had] fatty liver, she was on a pile of medications, and she came to one of our group programs at Cleveland Clinic and used the power of the group and inspiration, and the education support, and changed her diet. The core of it is what I call the 10-day detox diet, which is essentially Paleo-ish. It’s no grains, beans, sugar, dairy, processed food, and so forth. And in three days, [she] was off her insulin. In three months, she reversed her heart failure, her ejection fraction went from on her way to a heart transplant to normal, her kidneys normalized, [and] her liver normalized. Here was someone who was on her way to a heart and kidney transplant, who became perfectly normal. Then over the course of a year, [she] lost 116 pounds, just using food and simple lifestyle interventions, and dramatically reversed her health situation and her biological age and ended up adding so much vitality to her [life]. Where she was on her way out [before], now she’s back, engaged in fully living her life.

So you see that. And she didn’t have any expensive things. She was part of a group; she didn’t even have one-on-one medical care. We did this for The Daniel Plan. People can do this together, and the beautiful thing about this is that the medical system is not going to save you.

Chris Kresser:  It might kill you, actually.

Mark Hyman:  It might kill you, exactly. Most of the things we’re talking about are things that we’re empowered to do that don’t need a doctor’s intervention.

Chris Kresser:  Yeah, amazing. And I have to say, I get a lot of books sent to me, as I know you do, Mark, and some of them I’ll read a couple [of] pages. This one I read from cover to cover, as I do with all of your books. I always know I’m going to learn something new, and I love your balanced approach. [It’s] very evidence-based and science-driven, with a lot of heart, too. Understanding that it’s not just about the technical things; it’s [about] things like social connection, how we relate to each other, how we show up in our own lives with a big heart. [It] is a huge part of this and just as important as everything else.  [It’s] a really important book, for our times, especially. Tell people where they can learn more about the book, and then, for the three people listening to this podcast who haven’t heard of you and don’t already know of your work, where they can follow you online and find more of your work and your books.

Mark Hyman:  Oh, it’s pretty easy. I’m not hard to find. My social media handle is Dr. Mark Hyman; that’s DrMarkHyman. My Doctor’s Pharmacy podcast [is] available wherever you get podcasts. DrHyman.com is my website. And my book, you can get pretty much anywhere you get your books. You can go to YoungForeverBook.com; there’s a lot of great bonuses there, or Amazon or your local bookstore. [It’s] pretty easy to find. It’s in Kindle; it’s in audiobook. I think you’ll find it very helpful. It’s kind of, to me, the culmination of my life’s work. It’s a really practical roadmap. It explains the science and the why, and then it explains what to do and how to do it. I think that’s really the whole goal here. It’s not some abstract book on longevity, and there’s a lot of those out there, and not reductionist, with just focus on one thing or one expertise, but [instead] really laying out the big perspective of, what do we know, how do we create a roadmap for health, and how do we understand our body’s owner’s manual so we can live a long, healthy, vital life and be in contribution to the world?

I’ll just leave you with a thought from Common who basically said, “Where are you going to leave your one grain of spiritual sand on the universal skills of humanity?” I think, for me, that’s it. How do we add value to each other to our lives? If you feel like crap and you’re sick, you’re not going to be doing much to help each other or the planet.

Chris Kresser:  Yeah, or even be able to show up for your kids or your partner or whatever it is. This is about enabling us to live our best life and make a contribution. I couldn’t agree more. And that’s something that’s worth fighting for, worth committing to, and worth dedicating your life to, right?

Mark Hyman:  Yep, absolutely.

Chris Kresser:  Well, thanks again, Mark. I always enjoy our conversations. Everybody, make sure to pick up a copy of this book. It’s essential, mandatory reading, I would say. And I don’t say that very often, as you know if you’ve been listening to this show for a while. So, [go to] YoungForeverBook.com. Pick up a copy. You won’t regret it. Mark, [I] can’t wait to see you next time. [It] seems like we’re doing this every couple of years because you have a habit of writing books.

Mark Hyman:  I might be over that for a minute.

Chris Kresser:  Yeah, I’ve heard that before, so we’ll see.

Mark Hyman:  I know, I know.

Chris Kresser:  We’ll see. You can’t help it.

Mark Hyman:  It’s a bad habit, yeah.

Chris Kresser:  It’s a good habit. I like your books. Well, thanks everyone for listening. Send your questions to ChrisKresser.com/podcastquestion. We’ll see you next time.

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