Why We Grow Old And How To Age Well

Coming up on this episode of the Doctor's Pharmacy.

We're in a remarkable time for aging. Now we're in a phase where the question is what are the right combinations of diet, exercise, food, supplements?

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Hi, this is Lauren Feehan, one of the producers of the Doctor's Pharmacy podcast. Did you know that the body has built-in systems to slow, and even reverse aging. When you activate these systems, you increase stem cell production, reduce inflammation, increase antioxidant enzymes, build muscle, lose fat, and increase cognitive capacity. Aging is inevitable, but maybe it's time we challenge our thinking on what it means and how we can age better. In today's episode, we feature three conversations.

From the Doctor's Pharmacy on why looking at aging through a new lens is vital for enjoyment of life in our later years.

Dr. Hyman speaks with Dr. David Sinclair on advancements in science that show us.

How we can live longer, with Dr.

Frank Lippman on practical tips for aging.

Well, and with Dan Buettner on the.

Importance of friendships and community as we age.

Let's dive in. We see increase in inflammation and aging. We see a decrease in mitochondrial function, which are these energy cells. So we lose energy. Basically, our engine gets, the carburetor gets full of whatever, and it doesn't work. We see hormonal changes, lower testosterone, higher cortisol, lower growth hormone, increased insulin, increased blood sugar. We see changes in the microbiome that degrade over time. We see changes in our ability to sort of metabolize things and toxins. These are all things that we can understand now with the science we have, which we couldn't even a few decades ago. It's what we've been doing in functional medicine without really understanding that much of the science because it's all emerging. But your work has really started out with looking at the mitochondria as a key to aging and that has sort of led you to some of these other linkages, right?

Well, mitochondria, I didn't set out to study mitochondria. It's how our research pointed in that direction that they were part of the puzzle. We started out when I was with Leonard Guarante, you mentioned my former mentor and still friend. We started out with the question, why do organisms grow old in the first place? Simple question. Very few people had actually asked it. And so we studied yeast cells from, you know, bakers and brewers use it all the time. Why do yeast cells not live forever? And they typically live a week. We actually we found out that these genes that you mentioned, sirtuins, are regulators of yeast aging, and we have seven of these genes in our bodies, and they do phenomenal things. They repair DNA, help telomeres, and one of the things we found they do very well is keep the mitochondria healthy. And actually we found what was surprising was how reversible the aging of mitochondria are in animals at least, and we're now doing human studies and clinical trials that within just a week of treatment with a molecule that, a few molecules that we've tested that enhance the function of sirtuins, whereas veratrol was a famous one we worked on. Now, NAD boosters all seem to be able to reverse mitochondrial dysfunction within days. And we never knew that aging was that malleable until then.

Yeah, we see it all the time. I see it, you know, treating patients where their literally biology can reverse at any time. You see people who are in their 60s who have all these end-stage diseases like heart failure and diabetes and severe obesity and hypertension and kidney failure. And you see these things go away when you start to modify these factors that drive inflammation and blood sugar and mitochondria.

It's pretty amazing. Yeah. Well, there have been a few paradigm shifts in the field. So when I started out, and this is we're talking about the early 1990s, the idea was our bodies are like cars. We eventually wear out. There's not much you can do about it. You can slow down the rusting. freen radicals, and that's about it. But what we discovered in the 90s, thanks to works by Cynthia Kenyon and Lenny Guarente and others, is that these genes sirtuins, and there are some others we can talk about later, I think. But these protective pathways exist. We didn't know that we had protective pathways. It's as though we've discovered not just that our bodies are better than cars, that we actually have inbuilt repair systems.

Yeah, it's like a body shop.

Like a self-cleaning oven, right? Yeah. And they get lazy if you're lazy. They get lazy if you become obese and don't eat well and if you eat too much. There are other things you can do to kick them into action with how you eat, what you eat. But also what we found is that they're basically inbuilt survival mechanisms that are very ancient. They're found in yeast cells and plants, in our bodies, probably our microbiome plays a role. And so we can basically make a call to the Pentagon of the body and they can send out the troops without actually damaging the body. You don't have to have a war to get ready for war. and these protect us against diseases and many cases reverse aspects of aging. Another paradigm shift was that we could delete the bad cells in the body, the senescent cells that accumulate. And there are some molecules in clinical trials as well that might be paradigm shifting. How do you delete those? Well, they're called senolytics. Senolytics, lytic, meaning lice, the cells kill them. And there are molecules that can do that. There are some natural molecules, quercetin, quercetin, from onions and apples to sativex, a drug on the market. We, well, actually work at the Mayo Clinic primarily, and Judy Campisi out at the Buck Institute found that you can treat animals and delete their senescent cells and they get younger.

So you basically like go in and like clean up all the bad cells.

Yeah, we call these the zombie cells. Senescent cells are zombie cells. They're half dead. They sit there, they should be dead. but they're actually causing havoc. They're secreting inflammation factors, cytokines that cause other cells to senesce and to become potentially cancerous. And when you delete them, mice live longer. And what's exciting about that technology, that science, is you can, instead of taking a pill every day, which is the kind of stuff that I work on, if their stuff works, you can have a treatment once every decade maybe, and that's it.

And the treatment is a drug? Is it a supplement? It's like quercetin, you say?

Well, you can supplement. There's nothing fully proven in humans yet. There are some early studies from the Mayo Clinic just this year, the study in humans came out that was promising from Jim Kirkland. But in mice, a lot of studies now point to this being a phenomenal way to address aging. So you have kind of different pathways.

You can work on at the same time, right? You can work on the killing all the bad aging cells and you can work on optimizing and revving up your engines, like tuning up your engine.

Well, we're in a remarkable time for aging because we've moved from just understanding what's causing it and how we might intervene to truly understanding what can be done. And now we're in a phase where the question is, what are the right combinations of diet, exercise, food, supplements, and eventually drugs that are on their way? And so I mentioned two paradigm shifts. There's a third one that maybe we can touch on later. Yeah. And that's reprogramming cells and with an understanding of actually what's controlling the clock of aging and how to wind it back.

Because you said, you know, this limit of 100 years or 120 is not necessarily a hard stop. There may be ways of understanding the aging process that we can interrupt that.

Well, there are plenty of animals and certainly species across the planet that live longer than we do. It's not a biological impossibility to live hundreds, actually thousands of years. There's even some corals that live for 10,000 years. So it's not a fact of life that we have to die at 120. If you remove predators and war and disease, species evolve longer lifespans. It's happening right now on a Japanese island where a lizard was released and it's got no predators. It's breeding slower and living longer. That's what happens and give us a.

Few more- It doesn't actually, it just sits there in the sun all day, right?

Well, you know, we don't have to necessarily live at the bottom of the ocean like a Greenland shark or on a rock. But what these organisms show us is that life, lifespan is malleable. It changes over millions of years, sometimes in the course of a few generations, as we're seeing with this lizard. What is happening? That's what I want to figure out. What is it about those organisms that we can learn from? And instead of letting us evolve, or having to wait for us to evolve over millions of years, why don't we just accelerate gene editing? Is it going to involve gene editing.

Or is it going to involve more of these other kinds of technologies?

I touch on gene editing in the book. In my lab, we're using gene therapy to kind of leapfrog and really see how powerful our genome can be. We're having some remarkable results in mice and truly reversing the clock of aging and seeing what can happen. And maybe I'll reveal that later.

Okay, it's fascinating. I have an APOE2 gene and a three, which is two is like the ones who can live forever, drink, smoke, and not exercise and live to 120. and then the four is the bad one, you get Alzheimer's. So how do I change my three out for a two? Can I do that? I'm gonna get a double two?

It'll be possible. Where we're at with gene therapy is, so there are a couple of drugs on the market that are used for rare diseases, because that's usually where new technologies are first used. There are scientists who could probably do this to themselves if they were crazy right now. The technology is there. Where we're not at, the science doesn't allow us to change every cell in the body right now. Even in a mouse where we've been studying this longer, and my lab does this every few weeks in the lab. The problem is we can infect about 30% of the cells and it infects and changes the genes in some organs more than others. So it's very easy to change most of the cells in the liver, but not so much in the muscle and the brain. And you only get one or two shots at it because an adenovirus, which is what carries the gene therapy, causes an inflammatory response.

Right, that's not good.

So, you know, I'm not planning on doing that anytime soon. But if I had a rare disease and it was going to kill me, or I was 95 and I had nothing else to lose, maybe I'd consider it.

Unbelievable. So, the whole goal here isn't just to extend lifespan, right? It's to extend health span, right? Which is how long? vibrant years you have. And, there was a lot of thinking that if we extend lifespan, there's going to be a lot of old people who are going to be sick and cost the system money and drain our society and that's not a great thing. And yet, there are others that sort of pointed to research that maybe that's not the case, that if we figure out how to create health, that we can do what we call rectangularize the survival curve. James Fries wrote about this decades ago where he talked about how people who didn't smoke, who exercised and kept the normal body weight, live longer and were healthier and just didn't get sick. They just basically fell off the cliff and died as opposed to long, slow, painful deaths. They died quickly, painlessly and cheaply.

Yeah, well, that's what the science is pointing to. And in my lab, we see that a lot. When we intervene with a molecule, we see those mice, they are healthier for longer. And actually, you know, when I talk to people about living longer and I ask, how long do people want to live? A typical answer is, oh, I wouldn't want to live over 100 because they people have seen what 100 year old looks like.

Right.

You know, God forbid that we get there. But what changes their minds is what if you could be 100 and still play tennis and hang out with your great grandkids and still be productive? You don't have to be earning a living. You can be helping the community, nonprofit work, and then everyone raises their hand pretty much. So it's all about health. And that's the key point. I want everybody to know that I don't know how to extend lifespan without keeping people healthy. In fact, the reason that's how you do it. That's how we do it. That's the only way we can extend lifespan, is to keep animals and eventually people free of disease for longer. And then eventually something gives out fairly quickly, typically. And that's the idea. You know, someone like my father, who's 80 now and still traveling the world and going out every night and hanging out.

Girlfriend 20 years younger and.

Well, yeah, multiple friends. I don't know if they're girl friends, but. But that's a life that. that I think is well lived. And if he can keep going and helping my family and his community, which he's doing for another 10 or 20 years, the economics show, and we've modeled this for Australia, we've done some, others have done this for the UK, GDP goes up. It's not that there's a drain at all. In fact, the amount of healthcare, it's 17% of GDP right now in the US. It's only gonna keep going up. The reason is we're getting older and sicker. The last 10 years of life can be spent in wheelchairs and not going outside and being spoon-fed. I've seen that with my grandmother. So my father's mother at 80 could barely walk. She was in a wheelchair, spent the last 10, 13 years of her life in a state that you wouldn't wish on your enemies. And the expense to keep her alive was ridiculous. My father, on the other hand, he's contributing. That's what I talk about in the book, is that the future is bright if we can tackle this problem, keep people healthy for longer. The problem is if we don't succeed, we have an issue too. The world's economy is going to be dragged down by all the sick elderly people that are coming along. It's true.

I just read a study the other day that was a macroeconomic analysis of chronic disease, just the United States, the direct and indirect costs over 35 years, it's $95 trillion with a T. That's over $3 trillion a year. And if we figured out how to fix that, We literally have money for everything we need in this country, infrastructure, free education, forgiveness of student loans, free health care for everybody.

Yeah.

Basic, you know, raising everybody out of poverty. I mean, it just would be a game changer, right? Yeah.

You know, I couldn't have said it better. One of the things that people challenge me on, they say, why work on aging? Don't we have more important problems? Global warming, species extinction. I'm all for that. I'm the biggest greenie and, you know, I was going to be an animal rights activist if it wasn't for working on aging. But I think the best way to tackle the problems we have is actually first solve the biggest drain on the planet, which is taking care of the sick and the elderly. And then, like you said, there's trillions of dollars. If we could just reduce one disease of aging by 10%, it's about $3 trillion over the next decade. We're talking about a lot more than that. And that's money you can use to fix the world.

And your thinking is actually the thinking that I think can solve the problem, because In medicine, most of the thinking is focused on disease. You're focused on the mechanisms of health.

Well, sure. I mean, it's important to know why people die. And we have a list of 14,000 diseases in the handbook.

155,000.

Yeah, but knowing why people fall off a cliff, I would argue it's also just as important, if not more important, to know what drove them to the cliff in the first place.

Yeah, so let's get down and deep a little bit. the thing you're working on now is similar to what you're working on around resveratrol, which is the active ingredient in red wine, except the equivalent amount of dose you'll use, I think, was like 1,500 bottles of red wine. So, it's not something people should try at home. Because that worked on sirtuins, it worked on mitochondria, but now you're working on a different mechanism, which has to do with increasing the function and health of mitochondria using a compound that helps increase NAD. Now, can you explain what NAD is? A little bit about why mitochondria is important. And before you do, I just want to sort of back up a little and say that all the studies on aging that have shown any benefit to increased lifespan in animals have all been often through calorie restriction, which means you eat less, like two-thirds, a third less, you live a third longer. And, and also new things like fasting, mimicking diets are being studied and other things related to calorie restriction. Now that that apparently affects the mitochondria. That's how it works. And that's really what you're trying to figure out. How do you get around having to.

Starve yourself all the time? Yeah. Well, a large part of it is mitochondria. They do other things which we can touch on. They probably do a hundred things that we're still working on. Let's go back to yeast, because I think that's a good framework. When we started in yeast, we didn't know why they were dying. We figured that out. It's mainly genome instability that that affects their cell identity and then they die. Discovering the sirtuins was a game changer because what we figured out was there are three levels to aging. There's the base level, which is the things that kill you, DNA damage, telomere shortening, mitochondrial dysfunction. Okay, that was pretty much worked out in the 90s. Then there was a level above that, that there are these regulators of aging. The sirtuins are major regulators. But then in the 2000s, my lab and others found there was this top layer, which is the environment. And when the environment is a little bit harsh, adversity, or even perceived adversity, it kicks these protectors into action, and then they slow down or reverse these causes of aging. So think of it as a hierarchy pyramid. So what you want to do is start at the top. So how do you trick the body into thinking that it's going to run out of food or that there's some other adversity? and we found in yeast cells, if you reduce the amount of sugar, getting back to sugar, they kicked into action the sirtuins. We'll talk about how they did that in a minute. And then the yeast cells lived longer.

They protected the DNA, they boosted mitochondria, and they lived longer. Wait, I just want to pause here. So sugar, you're saying, accelerates aging and.

Restricting sugar actually helps increase longevity in these. Well, certainly for yeast and a lot of data on humans that lower sugar is better and fasting blood sugar is lower is better too for longevity. But there are other ways to kick the sirtuins into action. So there's in humans, intermittent fasting is easier, I find, than calorie restriction. I tried calorie restriction for a week.

It was pretty hard. I met a guy once who said he's doing calorie restriction and he was a member of the calorie restriction society. I said, what do you have for breakfast? I have five pounds of celery and three pounds of tomatoes. And I'm like, No, thank you.

You're right. Well, eating is one of life's pleasures, but I find for me, if I skip breakfast, it's no big deal.

Yeah, so intermittent fasting is basically time-restricted eating where you eat within a certain time window of eight hours or 10 hours, right?

Yeah, there are plenty of varieties. I talk about them in the book. There are some other books that talk about that. You mentioned this many times on your show. There are some skip a meal protocols that skip two days a week. There are some people, Peter Attia's doing skip a week of food. He says after three days magical things happen. He thinks, I haven't tried that yet, but I'm going to. But yeah, no one knows actually what the optimal amount of fasting is. But what I can tell you is some time of being hungry is good. We can see that in our animals. There's no question if we give our animals, our mice, food every other day. They live longer. And in fact, if we gave them resveratrol and the combination of eating other every other day, we got some very long-lived mice and the combination was great. So that's one of the things I do to myself is give, have resveratrol and try to be hungry once in a while.

That's what the, the Okinawans do. They call hari hachi bu, which is 80% full. So you push yourself away from the.

Table when you're 80% full. There's a lot to that, for sure. You know, having a lot of food and glucose in your bloodstream. just not a good thing. So getting back to how to mimic this mimic exercise and diet, you can do it in yeast, you can do it in mice by either taking resveratrol. We showed that was one of the ways to activate sirtuin enzyme that protects the body. But we have something that's, I think, more interesting now, which is the NAD molecule you mentioned. So NAD, let me tell you what that is. Anyone who's studied biology will have heard of NAD but probably forgotten about it because it's a boring- It's a long cycle. Yeah, it's the molecule that nobody really wants to care about. What we discovered is that it isn't just a housekeeping molecule for biochemical reactions. Germans discovered 100 years ago you needed it for life. Without it, we're dead in 30 seconds. But what became interesting was, thanks to Lenny's work when I was in his lab, and then later in my lab, we showed that the NAD levels of an organism are important for controlling the sirtuin protective enzymes. And as they get lower, they're not as active. And if you can get them higher, either artificially or by exercising or dieting, they get kicked into action. We get the benefits of calorie restriction and exercise without actually having to do those things. And the. But they're added.

I don't think that's a good message.

No, I was going to add to that, which is. But if you add them to.

Is that it?

Well, we. We just published last last year, actually, in the journal cell, that if you have a mouse and you give it an NAD boosting molecule and you exercise, then they become super mice and they can run beyond.

Okay, that's good. So it's a lot of added value if you eat well and exercise. Oh, definitely. Because I remember reading original studies way back when, and I was like, wow, these mice were eating terrible diets and they were metabolically younger, they were fitter, and they didn't do any exercise. I'm like, Whoa, but then I was like, wait a minute, it's 1500 bottles of red wine. It's not gonna work.

Yeah, well, in the Rosenthal study, we did show that you could live, make a mouse live just as long on a high fat diet as a healthy mouse with Rosenthal in the diet. But I don't want to send the message that that's all you have to do and you'll be fine. No, there's other things that go wrong and we're not mice after all. And you feel better if you're healthier anyway, right? So anyway, getting back to the NAD. We can raise NAD in everything from a yeast to a human by giving them what are called NAD boosters. And these are either NAD itself or precursor molecules to allow the body to make NAD. The one that we use a lot in my lab is called NMN, nicotinamide mononucleotide is its real name. And the cells in the body take it up. There's a transport they get sucked up into cells and they immediately convert it into NAD. And we can see that there's a spike of NAD produced after NMN after about two to three hours, and then it eventually goes back down. But what we are seeing, especially in mice where we can take out tissues, or look at tissues in blood, is that that has phenomenal effects on the body's protective mechanisms through lightly through the sirtuins and mitochondrial activity.

Hey everyone, it's Dr. Mark. You're unique, which means your health and wellness plans should be unique too. But it can be tough to optimize your health and nutrition programs because it's often difficult to get the data you need. And even if you do get your numbers, you actually have to understand them and then be able to make meaningful action based on them. This is where Inside Trackers comes in. Inside Tracker is a wellness tracker that uses science and technology to deliver ultra personalized healthcare guidance. They can analyze your blood, your DNA, your lifestyle habits, and then give you actionable recommendations to help you meet your health and wellness goals. They'll tell you what you need to do and why, and you can track your progress and adjust your plan based on real-time feedback from your own body. Since 2009, their science team at Harvard, Tufts, and MIT have been bringing personalized nutrition and wellness to the world with their powerful evidence-based digital platform. InsideTracker is simple, customizable, and most importantly, it's based on you and your body. if you're curious about getting your own health program dialed in to meet your unique needs, I highly recommend checking out inside tracker. Right now they're offering my community 20% off at inside tracker.com forward slash Dr. Hyman. That's I N S I D E T R A C K E R dot com slash D R H Y M A N and you'll see the discount code in your cart. I think the other thing that that is important I've noticed for aging is this muscle. And, you know, I think we, we have a neglected organ, which is our muscle that we don't pay much attention to. And, and this condition that we get as we age, and it's inexorable. Like, if you don't do something to stop it aggressively, you will lose muscle. So you could be the same weight at 65 than you are 25, but your body be twice as fat. And it literally looks like a ribeye marble steak, as opposed to a filet mignon, which is what you want for your muscle with no. fat rippling through it that's all related to our diet and the lack of exercise. The two things I want you to talk about is the other side of the coin because protein you need and you want to get enough but not too much, but it's actually sugar and starch that drive this aging process. That combined with muscle strengthening and building as you get older seems to be some of the most important factors. Can you talk about those and how they relate to aging? Sure.

Well, sugar and starches are the devil. It's not even a debate. You've got to get as much of that out of your diet as possible. The protein is a harder one, how much protein you eat. I think as you get older, maybe decreasing animal protein, increasing a bit of plant protein, but still keeping those carbohydrates as low as possible or the sugars and the starches. I think the muscle issue is interesting because I've been doing acupuncture for so long and I really got into the functioning of the muscles. It's not just about building muscle. You want those muscles to work efficiently. What I see a lot of, especially as we get older and we have injuries, certain muscle groups tighten up. And when certain muscles tighten up and they don't fire, your body compensates and starts using other muscles. So let's say you have a tight hip or you have an ankle problem, your back muscles have to work more and then you start getting back pains and then maybe it goes up to your shoulders. So not only do you have to improve muscle mass or watch the loss of muscle as you get older, you've got to watch that functioning because as we get older, muscles tighten and the fascia tightens that thin layer that surrounds the muscles. When you cut open a chicken and there's this fascia around the muscles, that surrounds all our muscles in our body. And that as an acupuncturist and paying a lot of attention to that for the last 30 years, I've seen becomes a problem, especially as we get older and as we injure ourselves, and especially as we get older and we injure ourselves, we don't tend to recover as well. So it's really important when you do injure yourself to get some bodywork, to get some acupuncture, to get those muscles working efficiently again, and not just letting injuries sit there and not treat them. So I think it's not only building muscle mass and not losing or not losing muscle mass, but it's improving the muscle efficiency and that's keeping those muscles long and limber and watching that the fascia doesn't tighten.

That's a really good point, Frank, because I've had back issues my whole life from back surgery when I was 30 and recently had another back surgery. And now I'm getting treated by this physical therapist who's going into the fascia and rewiring things and then giving me exercise to do that compensate for the inactive muscles, exactly what you were talking about. And it's been only like three days of working with this person and I feel like a different human being. My body feels limber, lighter, opener. It's pretty amazing. So, I mean, not everybody can access that, but there's ways you can do it yourself with foam rollers and other things to really help. Okay, so let's talk about something that...

In the book, I talk about foam rolling. I think I just have to mention foam rolling because I think that is A lot of people can't afford going to some bodywork who does deep tissue work, but foam rolling is sort of the closest you'll get to going to someone who can do that. I really can't stress this enough. Recovering from injuries, recuperating, don't let those muscles tighten because the way our body works is to compensate and tighten somewhere else or overuse another muscle. It's really important to have those muscles working efficiently. It's one area of functional medicine that we didn't really get into in functional medicine. We talked about most of the other organs, but we didn't really talk about the functioning of the musculoskeletal system. I think that is really important.

Dr. Dean Popp:Well, it's definitely one of the nodes on the matrix, which is structural, but if we don't get into it enough, I agree. And actually, we're talking about building a whole course on structural modules, so I think that's very important. Dr. Mark:Let's talk about something that is a little abstract, but is really central to aging. and that is impacted by our diet, light, by exercise, by environmental toxins. And it's something called our mitochondria. And we've talked about that on the show a little bit before, but it's really important. So, what are mitochondria? Why are they so important in aging and disease? And how do we improve them? Because it seems to be the central feature of aging is the dysfunction and the loss of mitochondria. Right.

So the mitochondria are just the energy powerhouses in the cells and you have many in all our cells. And as we get older, their number decreases and their function decreases. So optimizing their function and trying to increase their number is one of the most important things you can do for aging. And interestingly enough, most of the things we've been talking about improve mitochondrial function or increase the number. We'll mention a few others we haven't, but it's a low carbohydrate diet or fats are what the mitochondria thrive on. Fasting is particularly good for mitochondria. Exercise, in particularly high intensity interval training, is really good for its strength training as well. So sleep, a lot of the lifestyle changes, you know, to me the mitochondria are what we in Chinese medicine talk about chi. We talk about the energy and how do you boost chi. To me the mitochondria are the Western equivalent to chi. That's your body's energy. And all these changes we talk about actually work with the mitochondria. What one of the things we haven't talked about and which actually are seems to work well or stimulate the mitochondria is this concept called homesis, which is...

I love that concept. What does that mean? What does that mean? I love that concept.

So homesis means sort of what doesn't kill you makes you stronger, basically.

Ah, that's perfect definition. That's the best definition I've ever heard.

That's a little bit of stress is actually good for you. for the body. Chronic stress, we know, is a problem and creates all these problems and it will help, won't help you age well, but a little bit of stress, homeostasis is good. And that's what fasting is. Fasting is physical homeostasis. It's a stress, it's a little bit of mild stress on the body and your body's response to that. And we talked about resilience, but your body's response to that will be is a positive response which stimulates all these factors that are good for aging. So we talk about fasting, we talk about a little bit of interval training where you push yourself a little bit more than usual. Going from hot to cold, so even just having an ice-cold shower after a hot shower. You know, I love going from a sauna, I've become obsessed with my sauna. going from my sauna jumping into some freezing cold water. So, you know, temperature extremes are another way of stimulating homesis.

I love that. I love that. I love going from my steam or sauna right into an ice bath.

And that's good for aging. I mean, that's good. That's homesis. So anything that's a little bit of stress on the body is good. And actually, what's interesting, I remember years ago at Jeff Blan talking about this or someone at one of the functional medicine conferences. With phytonutrients, a lot of the... homesis is really good for plants. So plants develop more antioxidants and protective phytonutrients to protect themselves from whatever they have to deal with to survive. spraying them with herbicides and that doesn't actually help them develop these phytonutrients to protect themselves, which actually end up being good for us too. The first time I heard about homesis was years and years ago at one of the functional medicine conferences where someone, I think it was Jeff, who talked about the importance of homesis on plants and developing phytonutrients that would then benefit us.

Yeah, it's really important to understand this idea because when you look at, for example, organic versus conventional plants or even wild plants even versus organic plants, the wild plants have way more by hundreds to thousands of times more antioxidant potential, phytonutrient compound, and they also taste better. What's interesting is that flavor goes along with phytonutrients. So, the flavor profile of a food is directly related to the the nutrient density and to the phytochemical content. So, if you go to a garden, which I did the other day in a friend of mine's garden, and you pick a really ripe tomato that's just ripened on the vine, you stick it in your mouth, and it's an explosion of taste and flavor and phytochemicals that is so different than these cardboard store-bought tomatoes that don't taste like anything. So, that's really the power of the little stresses. And, I think the strength training, the HIIT interval training, the fasting, the phytochemicals. These are all ways to actually improve this. I want to get into some tweaks that you have in your book that are really, really great. But before I want to talk about this idea called our epigenome and how that plays a role in our cells age and how we deteriorate. So what is an epigenome? What is its relevance to aging? How do we deal with it? What can we do to help fix it? Right.

So this is, you know, once again, one of the basic concepts that's come out of that hasn't come out of functional medicine, but what functional medicine treats that, you know, most of our genes we can change or we can manipulate in a way or upregulate or downregulate. So, for instance, you know, I actually just did a whole genetic test. I've got terrible genes. I knew I had terrible genes. You know, I have the genes, I have the APOE, I have the gene for Alzheimer's, I have heart disease genes. I mean, my genetic profile is terrible. But whether I get Alzheimer's and heart disease and all these diseases of aging is determined by how I live my life. These lifestyle factors, how I sleep, how I think, how kind I am to other people, how optimistic I am, what I eat, how I move my body, all are going to affect most of those other genes or the genes that we can affect to or upregulate or downregulate to affect our aging. So aging is probably less than 20% genetic. I mean, there's obviously a genetic component where you can't change those genes. I've got those genes. Oh, no, I don't know about those genes, but I've got enough genes that I know that I can change. You know, just because I have the APOE4 gene, just because I have some of these hot genes, doesn't mean I'm going to get it. Yeah, I probably, I'm losing it a little bit.

You seem all right. You seem all right, Frank. You're doing okay.

My heart may not be as good, but that sort of makes me want to just be more careful because you can change how you age. You can change the progression of these diseases. And I think it just all comes back down to these lifestyle changes that we all have to make. Sleeping is one of those things that I think is really, really important. And we don't talk enough about it, although more and more people are starting to realize the importance of sleep. But how you move, how you sleep, how you think, how you eat, when you eat, all these factors affect this epigenome, these malleable genes that actually can be upregulated or downregulated and affect how well we feel. and how we age.

I think that's really an important point, Frank, because you mentioned you have these predisposing genes, but they're not predestined. Exactly. They're not predestined to get these conditions. And what most people don't realize is that 80 to 90% of our chronic disease issues are not driven by genetics. They're driven by what we call the exposome, what our genes are exposed to and how those genes are expressed. and so if you're exposed to environmental toxins, if your microbiome is not healthy, if your diet's crappy, if you're not exercising, if your mental set, your mindset is not optimistic and focused and positive, it literally can change the expression of your genes by all these factors. And that's the beautiful thing about functional medicine. It teaches you how to optimize the function and the expression of your genes to improve their functioning and also to reduce the ravages of Aging. I'm very optimistic about you, Frank, because I didn't realize you were 66. I thought you were like 56. I mean, I know you're kind of older than me, but you don't look it. So, something's working. And I think for two old dudes, we were doing all right. I'm 60 or 66. It's working. And I think that people don't understand that what we see often as aging in America is abnormal aging. It's not really how we need to age, that we can age vibrantly. healthfully and be alert and focused and energetic even right up to the end. And, I've seen this in many people. I met this guy who was 95 years old the other day. He had a girlfriend that was 20 years younger than him. She was a young spring chicken at 75. He was just running around the room and I'm like, what's up with you? How do you do this? He says, Whatever I did yesterday, I just do it today. If I played single sentence yesterday, I do it today. and I think he just kept living his life and not mentally succumb to the idea of aging. And I, you know, I think you have to be more cautious, careful. You have to be more alert to what you need to take care of yourself. But I think, you know, we have so much potential to stop and even reverse the ravages of Aging. And I, you know, I noticed this to myself, you know, I, I am. Because of COVID I was locked at home like everybody else. I'm like, well, I'm not going to not exercise, and I got a zoom trainer and I really never had done weights before because I was, you know, I was running around on the road. I was, I didn't, I don't like it. I don't like it hurts. It's uncomfortable. I'd rather go for a bike ride, you know, play tennis. And, and I got, I got serious about it. And within a very short time, I noticed my body started to change. I literally put on 10 pounds of muscle. My, my, it was like, I, I was an incredible transformation, and it was just in a very short time. So I think we have the potential.

At any age to stop and even reverse these effects. Most of the things that people in the blue zones do to live a long time are also things that make you happy. I did another cover story for National Geographic on happiness. So the fact that they're so social that they make time for people, for face-to-face conversations, long lunches, and they live in villages where they bump into each other in the streets. And every day at five o'clock, they pour out into the streets and the little bars and that, and they make time for each other. And, you know, that feels good. We are a species that evolves socially connecting. And now we know very clearly that people who are well connected live eight years longer than people who are lonely, for example.

Yeah.

And it's just natural there. You also probably notice that people haven't imploded in their devices yet. And, you know, people do have cell phones there, but they're not on them all the time. And they haven't drank that poisonous Kool-Aid yet. You know, there are still shepherds. The real longevity phenomena in Sardinia is mostly among the males, you know, even though females live longer, but the males are really the longest lived people longest of men on earth are in right where you visit in Sardinia. So you start looking at their life. And, you know, even though it's Mediterranean, this is where you went in the blue zones, actually a Bronze Age culture. This is a group of people who broke away from what is today the boss country, made their way through what is today South France, Corsica, and set up shop 11,000 years ago. So they're not the same as Spain and France and the rest of Italy. It's a Bronze Age culture. And most Mediterranean cultures, the men are the sit at the head of the table when it's male dominated. But I don't know if you know, in Sardinia it's female dominated. So women are running the household and they're taking care of finances and up fixing the roof. And by the way, they're the ones that carry the guns. They probably never busted one up, but we've seen all these women busted out there because they're in charge of civil patrol. So, you know, what really surprised me that where men live the longest, women are in charge.

Women are in charge. That's a good lesson. I think that's probably a good lesson. If women were in charge, this would be a very different world. 100%.

I think, quite honestly, I think we'd all be better off.

I think you're right, Dan. I think you're right. I believe it. No, no, I agree. So, I think, you touched on something earlier, which is this whole idea of community and loneliness. And loneliness is among the biggest risk factors for death and for disease and social isolation. And we know from animal experiments that if you give all the same inputs, food, water, light, whatever, to an animal like a monkey, but you don't give it a mother as opposed to the monkey that gets the mother. They age rapidly. They look decrepit. Their immune systems don't work. I mean, it's extraordinary when you see the graphic representation in some of these studies. And I think we see that increasingly here. We've all become an individualistic culture. I mean, there's a lot to be said for self-expression, for autonomy, for self-realization, for individualism, but not at the expense of connection and community. And I think a lot of us have lived our lives, you know, going for that Holy Grail of success in whatever way you define it. And along the way, the debris of our life is the lost friendships, the lack of attention to the people that matter in our life, the lack of being present and connected. And that catches up with us, and that is actually a disease causing phenomena that literally affects our genes, our epigenetics, all of it is driven through our social network. And it, you know, our social threads that connect us are more important than the genetic threads in determining our longevity and our health. And that really is powerful. So, you know, how do you help people and what does the Blue Zones Challenge say about building this? Because especially with COVID increasing isolation and people getting locked down and, I just, it's just hard. I mean, I'm finding, you know, one of the biggest challenges for me, which is, you know, not a big challenge, but I just, I'm really having trouble with the masks, not because I don't think they're necessary or we should be using masks to, to reduce the spread of viral, viral particles and so forth. But I, I don't see people's faces anymore. I don't see that human expression. I don't see smiles. You know, like I went to shop and get something the other day and I told the joke to the lady at the cashier. and I could see your kind of eyes a little bit, but, like, I don't know if she laughed. I didn't. I just. All that natural sort of juice we get from interacting with humans, you know, even that we're not close to this part of our community is such an important nutrient for our souls, for our health, for our well-being how do we start to bring that back into our culture? What have you. What have you found works? And what do you help guide people to in the Blue Zones challenge?

I'm going to answer that on a macro and a micro level, and they're both important.

Okay.

I'm sure you've seen this study that the casual social interactions throughout the day, the more you have as a bigger predictor of longevity than diet and exercise. And I mean, just as you're saying, the interaction with the woman at the grocery store, your postman or your barista, very important. And I argue that that's very much a function of your environment. Again, if you live in a city like Tampa where you have to drive everywhere, you just don't have, you don't bump into people on the street. You're not seeing your postman except where if you live in a neighborhood like Boulder, Colorado or Santa Barbara or even where I live in Minneapolis or in where I live in Miami, I'm out in the streets all the time and I just have get more face time and a lot of social anxiety. is a function of being in the presence of other humans. So that's the macro answer. The micro answer, which I addressed in Blue Zone Solution, I'm sorry, Blue Zone Challenge, is that your immediate social circle, those four or five people who you spend the most time with, have a profound impact on your health. If your three best friends are obese, there's 150% better chance you're going to be overweight. alcohol use, drug use, unhappiness, and even loneliness is measurably contagious. That's actually Nicholas Christakis' work, not mine, but it underpins an important observation in the blue zones, especially in places like Okinawa with this notion of moai. People pay attention to who they're spending time with, and their immediate friends tend to be eating the same healthy diet. They tend to be walking places. They tend to care about you on a bad day. They tend to people you can have meaningful conversations with. In the Blue Zone Challenge, this is the time of year people start making resolutions. As we all know, resolutions have a half-life of about a week and they're gone in four weeks. Instead of getting on the new fad diet, I take people through a process of A, identifying the type of people who are going to favor your health and longevity, and B, give them a strategy to actually bring them in their circle. And because when it comes to longevity, there's no short term fix other than not dying. There's nothing you can do this month or this year even that's going to really favor your life expectancy in 30 years. So if you want to live a long, if you want to do things that are help you live longer, you have to think in terms of decades or lifetime. What am I going to do? that's going to constantly influence me to eat better, move more, socialize more, live and express my sense of purpose and building that immediate social circle, that three or four friends who care about you on a bad day, that's about the most powerful, lasting thing you can do.

Yeah, that's really important. I think you mentioned it. I think we don't really cultivate that and prioritize that in our culture, in our life. and, you know, how many people, I think I've seen them date on this, but how many people can actually say that they have someone in their life that they can call up and tell anything to?

And, you know, this is Robert Putnam, a Harvard researcher. He wrote Bowling Alone. And in Bowling Alone, and it was written in the late 1980s, he calculated that we, each American, have about three good friends or friends you can count on on a bad day. I keep bringing this up. What that means is you've just broken up with your partner and you're crying your eyes out. You know, we all have backslab buddies, you know, who sure they'll have a free beer with you on a good day. But I mean, friends who will listen to you weep and, you know, if you need to actually borrow money or you just need to pour your heart out, those are the kind of friends I'm talking about. So it was three people in the 1980s, we're now down to an under two friends like that. And I still, again, I believe it boils down to this thing.

More friends on Facebook, but no actual friends.

No friends like Mark Hyman and Dan Buettner.

You know, it's true. It's true. I find, you know, I actually COVID and, you know, went through a divorce and it was rough. And I called my circle together. And, you know, I have a lot of guys I've known for a long time, really close friends. We do men's work together. We know each other for 30, 40 years and we see each other periodically. So I invited these friends to be part of the circle every week and we do a Zoom hangout with seven of us who've known each other 30, 40 years. And it's really about being transparent and honest and holding a container for each of us to be seen and heard, supported, loved. Sometimes we give each other advice, sometimes we just listen. And I mean, I don't even know how it would have gotten through the last year without it. and I feel so blessed. I mean, just so beyond blessed to think about that. And I think it, you know, the part of, part of my, my early, my early, evolution was really understanding the importance of community. And so I've spent a lot of time in my own life cultivating and nurturing and watering those friendships. So, you know, after 40 years, I can call them up and go, hey, I need you. And, and what was amazing was that I thought, oh, you know, just going through a hard time and, you know, they're gonna do it for me. But then I was like, well, can we do it maybe every other week for an hour? They're like, no, no, no. Let's do it every week for two hours. And I'm like, okay, okay. And then, like, they all were so in. And I was like, wow, we all need this. We all want this. So I encourage you to think about how do you start to cultivate that and find those people and develop those relationships? And it really is the, it's the medicine that we're missing in our society.

I would, I would argue that that investment is way more important than trying to get on a diet or a supplement or training for a marathon or all these other deep fall. You know, the thing- I can go.

Eat my chunky monkey ice cream now.

A little bit of that. But you start asking yourself why you look at the budget of the Processed food industry marketing budget and it's north of $15 billion a year. So, and then the beverage association, another $10 billion a year.

And then the exercise- what is the broccoli about? Broccoli is $100 billion, right? Broccoli advertising?

I think it's $100.

But also, good luck.

The exercise industry, another $120 billion. So, we are constantly marketed these ideas of what make us healthy. There's no money. in creating a men's group. Nobody makes money off of that. Nobody makes money off of you knowing your sense of purpose and living it. Nobody makes money off of you putting your family first or investing in relationships beyond just the back and forth commerce of it. So it takes people like you with you have a powerful mouthpiece here to not even tell people about it, but I mean you also know the underpinning science and you're a doctor. You have MD after your name so people listen to you and that's powerful. I also think it's, you know, for 40 years we've looked for the answer of better life in technology and I think technology can help a little bit but when you look back in places like the Blue Zones, those people are doing things a certain way that is evolved over 11,000 years. And they're still at work today in people's life because they are working. And to pay attention to this idea of a guy will stop in the middle of the day and just talk to you or they feel a certain way and there those those practices are around because of a certain social evolution that they've worked and we ought to be paying more attention to that in my opinion.

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