Longevity 101: a foundational guide to Peter's frameworks for longevity, and understanding CVD, cancer, neurodegenerative disease, nutrition, exercise, sleep, and more (re-broadcast)

View the Show Notes Page for This Episode https://peterattiamd.com/longevity101/?utm_source=podcast-feed&utm_medium=referral&utm_campaign=240729-pod-longevity101&utm_content=240729-pod-longevity101-podfeed Become a Member to Receive Exclusive Content https://peterattiamd.com/subscribe/?utm_source=podcast-feed&utm_medium=referral&utm_campaign=240729-pod-longevity101&utm_content=240729-pod-longevity101-podfeed Sign Up to Receive Peter's Weekly Newsletter https://peterattiamd.com/newsletter/?utm_source=podcast-feed&utm_medium=referral&utm_campaign=240729-pod-longevity101&utm_content=240729-pod-longevity101-podfeed In this special episode, Peter provides a comprehensive introduction to longevity, perfect for newcomers or those looking to refresh their knowledge. He lays out the foundational concepts of lifespan, healthspan, and the marginal decade. Additionally, Peter discusses the four main causes of death and their prevention, as well as detailing the five key strategies in his longevity toolkit to improve lifespan and healthspan. Detailed show notes provide links for deeper exploration of these topics, making it an ideal starting point for anyone interested in understanding and improving their longevity. We discuss: Key points about starting exercise as an older adult [2:45]; Overview of episode topics and structure [1:45]; How Peter defines longevity [3:45]; Why healthspan is a crucial component of longevity [11:15]; The evolution of medicine from medicine 1.0 to 2.0, and the emergence of medicine 3.0 [15:30]; Overview of atherosclerotic diseases: the 3 pathways of ASCVD, preventative measures, and the impact of metabolic health [26:00]; Cancer: genetic and environmental factors, treatment options, and the importance of early and aggressive screening [33:15]; Neurodegenerative diseases: causes, prevention, and the role of genetics and metabolic health [39:30]; The spectrum of metabolic diseases [43:15]; Why it's never too late to start thinking about longevity [44:15]; The 5 components of the longevity toolkit [46:30]; Peter's framework for exercise—The Centenarian Decathlon [47:45]; Peter's nutritional framework: energy balance, protein intake, and more [58:45]; Sleep: the vital role of sleep in longevity, and how to improve sleep habits [1:08:30]; Drugs and supplements: Peter's framework for thinking about drugs and supplements as tools for enhancing longevity [1:13:30]; Why emotional health is a key component of longevity [1:17:00]; Advice for newcomers on where to start on their longevity journey [1:19:30]; and More. Connect With Peter on Twitter https://twitter.com/PeterAttiaMD, Instagram https://www.instagram.com/peterattiamd/, Facebook https://www.facebook.com/peterattiamd/ and YouTube https://www.youtube.com/channel/UC8kGsMa0LygSX9nkBcBH1Sg

• 0:11Speaker 00

  Hey everyone, welcome to the Drive Podcast. I'm your host, Peter Attia. This podcast, my website, and my weekly newsletter all focus on the goal of translating the science of longevity into something accessible for everyone. Our goal is to provide the best content in health and wellness, and we've established a great team of analysts to make this happen. It is extremely important to me to provide all of this content without relying on paid ads. To do this, our work is made entirely possible by our members, and in return, we offer exclusive, member-only content and benefits above and beyond what is available for free. If you want to take your knowledge of this space to the next level, it's our goal to ensure members get back much more than the price of the subscription. If you

• 0:54Speaker 00

  want to learn more about the benefits of our premium membership, head over to peterattiamd.com/subscribe.

• 1:04Speaker 00

  Welcome to a special episode of The Drive. For today's episode, we're going to do something a little bit different. This is an episode that kind of reads more like an AMA, where I'll be answering a set of questions, but it's going to be available to everyone, not just to our subscribers. Typically, of course, our episodes are really kind of deep dive conversations. That's what we're really known for. But we also get a lot of questions from maybe people who haven't been listening for long, asking something akin to, hey, where do I begin? So today's conversation is really intended to serve as a starting point. It's also a great thing that you can have if you have a friend who you're trying to introduce to these topics and you want to get them kind of up to speed. This is a great sort of longevity 101, as it were. We kind of lay the foundation for how I think about this,

• 1:48Speaker 00

  the structure that I apply to longevity, explain the various concepts of lifespan, health span, the four horsemen of death, marginal decade. We talk a little bit about the tactics. We talk about these five things of exercise, nutrition, sleep, drugs, and supplements, emotional health. And since this is obviously based on the scope, a rather superficial treatment of these concepts, the show notes-

• 2:10Speaker 01

  Notes are going to be quite detailed and will actually point you in the deeper direction of anything that is covered. So again, if you're feeling overwhelmed about some of our content, we really hope that this is an episode that's going to help give some of the foundational information that allows you to then appreciate some of the deeper dives that we are more commonly doing. So without further delay, I hope you enjoy this special episode of the drive.

• 2:39Speaker 01

  Peter, welcome to a special episode. How are you doing?

• 2:41Speaker 00

  Great.

• 2:42Speaker 01

  Awesome. Well, for today's episode, we're going to do something a little different. One thing we know and we can hear from people is if you look at podcasts, sometimes podcasts aren't the best way to learn about information. And part of that is because each week we cover a different topic in different detail and it may be cancer one week, exercise the next week, Alzheimer's, whatever it may be. And we go into different levels of detail. And so we also know we have newer people who are listening and sometimes they can be a little overwhelmed by all the different things. And so what we wanted to do was record an episode, which is basically longevity 101. And so we're just going to go through core lifespan, health span, each of the tactics and just touch on the core frameworks to

• 3:26Speaker 01

  give people kind of a foundation of how they can think about their own longevity and also how they can think about when they listen to the podcast, how these different pieces fit together. And so if you've listened since episode one, you might not need to listen to this one, but it might be one you share with someone to be like, hey, this is what this guy talks about. So we're going to hit all the five tactics, some real basic questions, but it should be pretty simple, pretty high level. So with that said, anything you want to add before we get into it?

• 4:00Speaker 00

  I mean, simple and high level aren't typically words I associate with very well. So I'm a little gun shy about how we do this, but let's give it a shot.

• 4:10Speaker 01

  So you're saying the first question that I should ask is what did you eat today for lunch? And why should everyone eat that for lunch every day as well?

• 4:19Speaker 00

  Absolutely. That would be a great question.

• 4:21Speaker 01

  Perfect.

• 4:22Speaker 00

  I think I've already forgotten what I, no, I remember what I had.

• 4:26Speaker 01

  All right, we'll save that for the nutrition section. But starting off with just a few foundational level questions, the first being, how do you even define this word longevity? It's a word that gets thrown around a lot, means different things to different people. I think it'd be nice just to be like, for this conversation to anchor what we're talking about. How do you define longevity?

• 4:46Speaker 00

  I don't make an argument that my definition is the best definition, but I agree with the idea that whenever someone is talking about it, it's worth asking them what they mean by it. And it's also why I tend to bristle at the association with longevity. Because, you know, if someone says, oh, are you a longevity doctor or something like that? I have no idea if they know what longevity means according to my definition, which again is not to say it's the right definition, but it's the lens through which I think about it. And therefore, everything I talk about, any question I answer will be through the lens. So the way I think about it, and I suspect the way some others do as well, is that longevity is, well, it's a function. So again, I tend to think of things mathematically made up of two vectors.

• 5:31Speaker 00

  And one of these vectors is lifespan, and one of these vectors is health span. And both of these vectors are necessary to demonstrate the function of longevity. Now, one of these vectors is much easier to understand because it is discrete, it is binary, and it is objective. And that is the lifespan vector. So there are some edge cases, but for the most part, you are alive or you are dead. And we think of that through the lens of death certificate death. Again, we could talk about an edge case. You can have an individual who is brain dead, but who is being kept alive.

• 6:14Speaker 00

  And we could debate whether that person is dead or alive. But I think for most people, there's very little confusion about what it means to be alive or dead. And notice that lifespan says nothing about the quality of a person's life. We'll save that for a second. But in a nutshell, that is lifespan. It is to be respiring or not to be respiring. And it is, again, one of the vectors of longevity. So inasmuch as we want to increase longevity, We presumably want to have something to do with increasing lifespan. The second vector that makes up this longevity function is the health span vector. This is far more complicated to explain. It is far more subjective.

• 6:56Speaker 00

  It is analog as opposed to digital, meaning it is not discrete on off. It is variable. And it also has three components in the way that I think about it. So one of those is a physical component. One of them is a cognitive component. And one of those is an emotional component. Now, in the first version of Outlive, when I wrote it, or maybe it was the second version, but not the version that got published. I went to great lengths to describe that the cardiorespiratory death, the I'm not aspiring death certificate death as type one death.

• 7:37Speaker 00

  And then I went into great machinations to talk about the three types of decline in health span as physical, cognitive and emotional death. And I think for probably good reason, everybody, the publisher and Bill, everybody really pushed back on that and they thought it was a little too morbid to talk about physical death as the death of your exoskeleton and cognitive decline. And I think they were right. I think that death was probably too strong a word there. But my point was that all of those things can be robbed of a person. And even though they're still technically alive, their quality of life has been sapped. So let's not think of it that way.

• 8:19Speaker 00

  Let's think of it as you have these three sub vectors of the vector health span. And each of those, there are ways that we can try to quantify them. But ultimately, I think people will have their own subjective assessment of what it means to be physically healthy, or what it means to be cognitively healthy, or what it means to be emotionally healthy. I think another thing that's worth pointing out here is that two of those three inevitably decline with age. So the physical component of health span, which I'll define in Some detail in a moment and the cognitive component of health span. They very predictably decline with age. Now that doesn't mean that everybody's decline at the same rate.

• 8:59Speaker 00

  And that doesn't mean that for everybody, the decline reaches a level that is quote unquote pathological. But it simply means, and I was thinking about this today in the gym, actually. I was like, wow, it is really so obvious to me with each passing day that I am completely past my prime physically and cognitively. And I will never again be as physically strong, fit, flexible, free of pain. Like pick your metrics that all make up physical health span. I will never again reach the pinnacles that I had reached in my late teens and twenties. And similarly cognitively, I'm basically a moron compared to the person I used to be.

• 9:42Speaker 00

  In terms of processing speed, problem solving, just raw intellectual horsepower. Those things are going to decline even further. Now there is more nuance to this because there are certain things physically today that I think I actually do better than I did before. In other words, you take advantage of the fact that as you're getting less explosive, less powerful. Well, you can still kind of maintain strength. And if you learn to move more intelligently, you can actually become more effective. And similarly, as our intelligence transitions from a more fluid form when we're young to a more crystallized. Experiential form when we're older, we still have remarkable ability to contribute.

• 10:25Speaker 00

  But there's no denying that on some of the prime levers against which you would evaluate these. We're in a state of decline. Conversely, the third part of health span, which is emotional health. It actually doesn't really tie to age much at all. Depending on how you evaluate it, it almost seems to have a U shaped curve. Not a really big obvious U, but kind of a dip in, I think statistically, probably the late forties. And then a gradual rising again. So one of the things that I always try to remind myself and then remind my. Patience is this is something we can really look forward to provided we do the work.

• 11:04Speaker 00

  I can be emotionally better off in a decade than I am today, and I am certainly better off today than I was a decade ago. So I would say that that is at the highest level how I describe longevity. And therefore, when a patient comes to me and says, I'm interested in longevity. I want to make sure that what they're interested in is what I understand because there are many other definitions of longevity out there. And if your definition of longevity is I want to live to be 200, I wouldn't obviously be able to help you. So the way I think about it is longevity means how do we live longer? I think that means years longer, a decade longer. It doesn't mean a doubling of lifespan.

• 11:47Speaker 00

  And how do we reduce the rate of decline of health span? That would probably be the most operative way to talk about it. So that's obviously very verbose and that's why I think it's not something that you explain very quickly to somebody. But given that that's the purpose of what we're talking about today, I think it's probably worth going into that detail.

• 12:09Speaker 01

  To double click on that, because you kind of at the end there mentioned where I feel like a lot of times when longevity and that word gets thrown around. It is on the how long you live side. So I think it's worth double clicking. Why do you think it's so important for someone to not only care about how long they live? The lifespan side, but also the health span side that you said there, and also how well they live.

• 12:33Speaker 00

  There are several reasons for this to be relevant. First, you can think of this kind of at the level of a thought experiment. So in the book, I write about the Greek god Thithonus and how he wished for immortality. He was of course granted his wish, but because he had forgot to ask for eternal youth. He became this indefinitely suffering human being who continued to age in perpetuity while his body declined. So just sort of theoretically, I think anybody who thinks about it for long enough would realize that. Any desire to live longer has to be accompanied by a desire to preserve health

• 13:15Speaker 00

  span. I believe that anybody who thinks they want to live to be 200 implicit within that I hope is the desire to function as someone who is much younger. If a person says to me, I want to live to be 95. Well, I'm assuming, and if not, we'll tease this out. I'm assuming they don't want to look like most 95 year olds. What I assume is I want to live to be 95, but I would hope that in the final years of my life, I function like a 75 year old, a healthy 75 year old. So that's why I think the second thing here is, and the reason at least for me, that health span is such an important focus. We're going to talk, I'm sure about medicine 2.0 versus medicine 3.0, but one of the most

• 14:00Speaker 00

  important concepts within medicine 3.0 is an equal obsession with health span as lifespan. And again, health span by itself is valuable at any given age, whether it's 40, 50, 70, or 80 to for your age, have a better physical body, a better cognitive mind, better emotional health always exceeds being below it. It's so self evident, it doesn't require stating it. Secondly, all the things that you do to improve your health span are two fers. Anybody who works for me knows what a twofer is and a threefer and a fourfer and how much

• 14:43Speaker 00

  I hate one fers. So a twofer means you're getting a two for the price of one. So when you do all those things to improve your health span, you are also improving your lifespan. You could make a case that most of the benefits in lifespan, roughly, I would say three quarters of the benefits you can get towards a longer life come solely from pursuing better health. I want to say that again, because I think it is, for me at least, it's such a profound statement. If you never thought once about trying to live a longer And focused relentlessly on how can I improve my strength, my endurance, my stamina?

• 15:28Speaker 00

  And again, all the nuance around these things, my balance, my coordination, my processing speed, my working memory, my emotional health, my happiness, my relationships. If you only focused on those things and never once thought about heart disease, cancer, Alzheimer's disease specifically, I still believe you would capture three quarters of the way towards optimizing your lifespan. I think it's a bold statement. I can't confirm that that's exactly correct. That's not a studyable question, but my conviction is quite strong that pursuit of health span is valuable in its own right, even if it didn't lengthen life at all. And the fact is, it probably does.

• 16:11Speaker 00

  And it probably does to a greater effect than all of the efforts that largely medicine 2.0 puts directly into lifespan extension.

• 16:20Speaker 01

  You hinted at it there, and so I think it's worth just going into it. You've written about it too, but do you want to talk real quick about medicine 1.0, 2.0, 3.0?

• 16:30Speaker 00

  Yep. So medicine 1.0 is the type of medicine that dominated for virtually all of human existence. So if we argue that humans have been around, Homo sapiens have been around about 250,000 years, from the arrival of our species until the latter part of the 19th century, we were practicing this thing called medicine 1.0, which truthfully wasn't medicine in the way that we think about it today. It wasn't scientific in the way that we understand science today. It was the best that humans could do, missing this tool, missing this tool of inference, and relied on a belief about perhaps gods, spirits, humors.

• 17:14Speaker 00

  And, you know, to be just blunt, was largely ineffective. And so the doctor of the past didn't have any tools, in large part because they didn't have any understanding of what was going on in terms of disease processes. So not surprisingly, humans didn't live that long on average, and the median life expectancy would have been into the late 30s or early 40s. The causes of death were typically related to communicable diseases, infections.

• 17:44Speaker 00

  And death associated with child mortality and maternal mortality. So just the process of having a baby was incredibly dangerous to both the mother and the baby. And obviously, that heavily skews lifespan data. If you're killing young mothers and babies in the process of having babies, you're really bringing down lifespan and life expectancy. And couple that with infections, communicable diseases and trauma. And I think most people aren't surprised to know that, yep, that's pretty much how people died. And then, of course, after the Civil War and we move into the latter part of the 19th century, a couple of things start to come together. Now, the first of these actually happened in the 17th century, but it wouldn't become

• 18:27Speaker 00

  germane to medicine until 300 years later, 200 years later, rather. And that was Francis Bacon codifying the scientific method. So, again, this is something we take for granted today, but this idea that you would make an observation, which is what science is all about. You observe something around you, you observe something in the natural world, you form a hypothesis about why it is happening, you design an experiment that is equipped to test the hypothesis, you conduct the experiment and measure the outcome, and you compare the results of the experiment to the prediction of the hypothesis.

• 19:10Speaker 00

  And that is effectively the framework for what science is. And so with that as the scaffolding upon which people could begin to make inference, you now layer on some other remarkable discoveries and insights. So a creation of the light microscope, the advent of germ theory, and ultimately the development of antimicrobial agents. All of these things collectively, I think I would add to that, just the practice of sanitation led to a remarkable change in the trajectory of human lifespan. And of course, it's so remarkable that if you go from the late 1800s until, you know,

• 19:55Speaker 00

  fast forward just 100 years, which again is a sliver of time across a 250,000-year timeline. Human lifespan approximately doubled. Three, four, five generations to double human lifespan that had previously been unchanged for hundreds of generations is a remarkable feat. And we call this new system of medicine, medicine 2.0. Now, there's lots of more nuance to get into medicine 2.0. Medicine 2.0 ultimately developed even more remarkable statistical tools that allowed for things called randomized controlled experiments, or RCTs, randomized controlled trials.

• 20:34Speaker 00

  And this really allowed medicine 2.0 to flourish and become supercharged. And obviously, for the most part, medicine 1.0 was completely displaced by this. Now, that doesn't mean that there aren't still some quacks out there that practice witchcraft. But for the most part, when a person has an infection, when a person has congestive heart failure, when a person is in renal failure, when a person has appendicitis and needs to have their appendix removed, when a woman has a complicated pregnancy, all of these things now for people who are in the developed world are really easy things to manage using the toolkit of medicine 2.0.

• 21:18Speaker 00

  So again, medicine 2.0 was and remains an enormous success. And I certainly wouldn't be sitting here talking without medicine 2.0. I would likely have been dead already, as would you have. So why do we need to go any further? Why do we need a medicine 3.0? Well, for all of the successes of medicine 2.0, it has indeed had a couple of obvious and notable failures. The most obvious is that lifespan has largely faltered. So there really has not been any extension of lifespan beyond that, which came from the eradication of the conditions that led to the demise of most people between the

• 22:03Speaker 00

  Civil War and the end of the First World War. In particular, the types of diseases that kill people today are very different types of diseases. From those that killed people 150 years ago. So the leading causes of death, which I describe as the four horsemen of death, are the diseases of atherosclerosis, so coronary artery disease and cerebrovascular disease, cancer, the neurodegenerative diseases and dementing diseases. So Alzheimer's disease, Parkinson's disease, Lewy body dementia, vascular dementia, frontotemporal dementia, all of those diseases. And then the slew of metabolic diseases that while directly not responsible for an enormous number of lives lost compared to the other categories,

• 22:49Speaker 00

  indirectly contribute immensely by amplifying all of these. Now, there's a couple of other things I haven't mentioned there at the population level. Chronic obstructive pulmonary disease is also an enormous cause of death, but its cause is almost exclusively related to cigarette smoking. So I don't really hold medicine 2.0 particularly responsible for the failure of mitigating that. That's really more of a public health question. If people don't smoke, they don't get COPD, even though COPD is one of the leading causes of death. There are, of course, accidental deaths, and we can spend some time talking about those later because there's an enormous spread of what those look like across lifespan and, of course, by geography.

• 23:32Speaker 00

  In essence, the purpose of medicine 3.0 is to try to address where medicine 2.0 has fallen short. It's not to replace medicine 2.0. I certainly, from time to time, hear feedback from people who I think misunderstand the arguments I've tried to lay out. And there's nowhere that I'm suggesting that we need to do away with medicine 2.0, that we don't want the system as it exists today in its capacity to do what it can do. What I argue is that we need to shift resources away from solely focusing on medicine 2.0 to focusing on what we'll talk about in a minute, which is medicine 3.0. So if we're putting 100 units of resources today into medicine 2.0,

• 24:16Speaker 00

  I think most economists would argue that's still too many units of economic input. In other words, healthcare makes up far too big a section of the economy. So maybe instead of it being 100 units that go into healthcare, it really ought to be closer to 60 units that go into healthcare. And I would argue further, maybe 30 of those units should be aimed towards medicine 3.0 and 30 of those units should be aimed towards medicine 2.0. Because when it hits the fan and something goes really wrong, trauma, infection, heart attack, by all means, you want medicine 2.0 there to backstop those things.

• 24:57Speaker 00

  But medicine 3.0's job is to make those encounters with medicine 2.0 less frequent, less severe, and later in life. That is effectively the difference. The final point I'll make on that is kind of just briefly explaining what medicine 3.0 is, which is, because at this point, it's self-evident. It almost doesn't need to be explained. Medicine 3.0 really has two main hallmarks. The first is that it is aimed at preventing, rather than treating, chronic disease by acting early, acting aggressively, and tailoring the therapies to the individuals based on the best available evidence, which is not necessarily going to be derivable

• 25:42Speaker 00

  from randomized control trials. And the second pillar of medicine 3.0 is that health span is to be given at least as much effort and attention as lifespan. This is, again, another enormous difference between medicine 2.0 and medicine 3.0. Medicine 2.0 does not place emphasis on health span. Its emphasis on health span is anywhere from zero to very small, depending on the subspecialty. So there are certainly some physicians whose practices do take them a little bit into the arena of health span. But outside of, for example, physicians or healthcare providers who work specifically in the arena of mental health,

• 26:26Speaker 00

  Again, it's relatively low. Obviously, orthopedic surgery is a discipline of medicine that is more squarely featured in the health span arena. But for the most part, most of the healthcare dollars are spent on addressing and trying to elongate lifespan. And I would argue that we need to be putting just as much effort into health span. That's the fundamental difference between medicine 3.0, 2.0 and 1.0.

• 26:52Speaker 01

  To double click on the four horsemen just a little bit, you mentioned what those four are. But do you also want to talk a little bit about for each of them? What we know in terms of prevention? So if medicine 3.0 prevention is really important, how do you think about? Our knowledge of those diseases as it relates to someone who is trying to live as long as possible?

• 27:16Speaker 00

  Sure, we'll take them from the top. So the atherosclerotic diseases, along with the fourth horseman, which is the metabolic diseases are probably the two that we have the most insight into as far as what are the pathophysiology drivers? And therefore, we either theoretically or in some cases practically also have, I think, the best insight into how to prevent them. So ASCVD is a disease that has both a genetic component and an environmental component. But it really doesn't have much of a component of luck as far as we can tell. So stochastic processes involving mutations doesn't seem to play a role.

• 27:57Speaker 00

  There's just pure causality from the standpoint of environmental triggers and from genetic inheritance. So both of those factors play through three pathways, all of which are important. So first is a lipoprotein pathway. Second is an endothelial pathway and third is an inflammatory pathway.

• 28:22Speaker 00

  But I realize as I'm saying that it doesn't make a lot of sense. So I'm going to try to step back and put this into English. The three things that have to happen for atherosclerotic disease are as follows. The first is a molecule called a lipoprotein, which carries cholesterol through the body. And specifically, a lipoprotein that has an ApoB protein on it. Because there are lipoproteins that don't have ApoBs on them, and we don't have to worry about those. But the lipoproteins that have ApoBs on them can enter the artery wall when the endothelium is intact. But they do so more prevalently and more easily when the endothelium is damaged.

• 29:06Speaker 00

  The endothelium is simply the lining of cells on the innermost membrane, I mean, closest to the artery or outermost from the standpoint of the artery wall. The one that is most in contact with the circulation. If those ApoB wrapped lipoproteins get trapped inside the endothelial layer, a chemical process known as oxidation takes place, and that leads to inflammation. What that means is the body thinks something is wrong and I need to fight it. Just as when you get an infection, a healthy immune system detects the inflammation caused by the microbial agent, and it sends the troops there to get rid of it.

• 29:49Speaker 00

  But in this case, the insult does not come from an infection. It comes from the oxidation of the cholesterol contained within the ApoB particle as it sits in the endothelium. And that process initiates a devastating cascade of events that ultimately can create so much damage in the wall of the artery that it can lead to a rupture of the plaque, which is the repairing process. The rupture of that plaque acutely leads to blood loss and ultimately oxygen loss to the muscles of the heart beyond the point of that blockage. That process is

• 30:32Speaker 00

  Known as a heart attack and about 50% of the time it is fatal the first time a person has one. So if you want to think about preventing cardiovascular disease, ischemic cardiovascular disease, you have to have an insight into all of those things. You have to be thinking about how do I have fewer ApoB particles? Because the more of those particles you have, the more of them that are going to enter the endothelial space. The data on this is as unambiguous as any data are in medicine from clinical trials, epidemiologic trials and Mendelian randomization.

• 31:14Speaker 00

  In other words, you have the only three layers of evidence you can ever look to, experimental data, MR and clinical Epi, and they all say the same thing. There is a log linear reduction in ASCVD as ApoB goes down. The second thing you have to do is you have to protect your endothelium. So anything that aggravates and weakens and makes the endothelium more vulnerable to penetration by ApoB is problematic. And the most common factors that we think are doing that are smoking, blood pressure,

• 31:54Speaker 00

  and very likely the metabolic conditions that cluster with insulin resistance, hyperinsulinemia, and type 2 diabetes. So some combination of elevated glucose, elevated insulin and other metabolic byproducts, such as homocysteine, uric acid, all of these things serve to weaken the endothelium along with elevated blood pressure and smoking. And that creates a greater susceptibility. Again, it's not surprising that all of those things pose about an equal risk to cardiovascular disease as does the presence of elevated ApoB. And then the third piece of the puzzle, and the one for which we really don't do much

• 32:36Speaker 00

  directly in the way of treatment, is the higher the inflammation, the more likely the Higher this is going to be. And the reason this is probably lesser of the three is with very rare exceptions, is it a direct therapeutic tool? In other words, we clearly therapeutically address the first two. We therapeutically lower ApoB, we manage blood pressure, we tell people to not smoke, which of course is a therapy. We use exercise and nutrition to manage metabolic health and even pharmacology. But directly from a pharmacologic standpoint, we don't really manage inflammation. We can. There are a couple of agents that are used, somewhat not impressively,

• 33:16Speaker 00

  and maybe somewhat on the margins impressively. But most of the evidence around reducing inflammation probably comes from doing things much more broadly around nutrition, sleep, and exercise that we've talked about elsewhere. So in a nutshell, that's really what it comes down to. And it's for that reason that I'm often making a very bold statement, which is even though cardiovascular disease is the leading cause of death, in men, in women, in the United States, but also in the world, it doesn't need to be. It really, really doesn't need to be. And it is a very bizarre tragedy that 19 million people a year still die from cardiovascular disease,

• 34:00Speaker 00

  given how much we know about what causes it and how many tools we have to prevent it.

• 34:06Speaker 01

  You kind of mentioned the first, second horseman there. How do you think about prevention for the others, which is neurodegenerative diseases and cancers?

• 34:16Speaker 00

  Let's take them in order. So cancer would be the next most deadly of the horsemen. And here is one where a lot of what I said with respect to heart disease is actually quite different. In heart disease, we really have a pretty clear sense of what the genetics look like. So there are a handful of genetic things like familial hypercholesterolemia, which is a very, very heterogeneous condition that raises Apolipoprotein B, LP little a, which we'll save for another time. We've got lots of content on that. But when it comes to cancer, we know that, boy, there are some really clear And obvious genetic drivers of cancer, like there are a handful of genes, some that many people have heard of such as BRCA1 or BRCA2,

• 35:00Speaker 00

  which are heavily associated with breast cancer, or Lynch syndrome, which would be heavily associated with colon cancer and other types of cancer. But for the most part, when we say that cancer runs in a person's family, we still aren't really even able to identify the genes through which this is transmitted. It appears to be very polygenic. Furthermore, while we know of at least two significant environmental triggers for cancer, smoking and obesity, and I'll say more about obesity in a second, we actually have very little to say about many other triggers. Despite what people would have you believe,

• 35:43Speaker 00

  we have very little insight about if at all foods, specific foods at isocaloric amounts. So we can talk about an abundance of food because that factors into the obesity trigger. But if we're talking about a bunch of people eating an isocaloric, energy balanced diet, again, despite all of the propaganda around this, oh, red meat this or soy that or whatever, there's actually just the scantest of evidence to suggest that any of these are promoting cancer in the slightest way. So when you take all of this together, what you realize is that, okay, smoking is clearly driving cancer. Obesity is clearly driving cancer.

• 36:26Speaker 00

  Not all cancers, but many cancers, about two thirds of cancers have a very strong tie to obesity. I think if you look under the hood of that, you'll realize it's probably not the excess fat per se, or the adiposity that's driving cancer, and rather it's the growth factors that are doing it. So obesity comes with more inflammation, comes with more growth factors such as insulin and IGF. And it seems more likely that those are the things that are actually leading the increase in cancer. But that leaves A bit of a vacancy in terms of what else explains it. And this is where a scientist like Burt Vogelstein and others would suggest that,

• 37:10Speaker 00

  look, there's actually just a component of really bad luck here. There are mutations that occur. Every cancer begins with a mutation. And most of those are somatic mutations. That means that most of those are mutations that occur in cells that were developed normally. So these are your germ lines, the cells you inherited. These were normal cells, but then mutations were acquired. And mutations fall into one of two categories. These are either mutations that are tumor promoting, so oncogenic mutations, or they are mutations of tumor suppression. So we have genes that are set out to suppress cancer.

• 37:54Speaker 00

  And if you get a mutation in one of those, the body loses the ability to suppress cancer. And then we get mutations in genes that turn cancer on. And again, a number of these are inherited, but many of them, most of them are acquired. And the what is vexing us still. And again, I think the best working hypothesis is that bad luck plays a lot of role in that. Now, it would be a topic for an entirely different podcast to look at other things that may be triggering those mutations. Again, in some cases, we know that viruses play a role in those mutations. But what I'm really talking about is where do the majority of these come from? That's an area of huge interest.

• 38:37Speaker 00

  And the other problem with cancer that also is not afforded to cardiovascular disease is the treatment options are less effective. So a person today who has advanced cardiovascular disease has a much better prognosis than a person today who has very advanced cancer. A person today with stage four, i.e. metastatic endothelial tumors. So that means a solid organ tumor like breast. Lung, pancreas, prostate, colon, one of the quote unquote bread and butter tumors. A person today who has one of those cancers that has spread from its original site to a distant

• 39:21Speaker 00

  site, that's metastatic or stage four cancer, that person has about the same 10 year survival as a person did with that tumor 50 years ago. They have a much longer median survival. They will live longer. They might live for five years instead of one year, and that's nothing to sneeze at, but they're not cured at any higher a rate. And obviously, that's a discouraging statistic. So as we think about cancer, we obviously think the first and most important thing is to do everything you can to avoid getting it. But as I alluded to, that playbook is not as thick as the don't get heart disease playbook. And that leads to a very controversial thing that I talk about, which is the importance of

• 40:05Speaker 00

  early and aggressive screening. And again, we don't have to go into that now. We've already devoted tons of content to the arguments for and against that approach. But hopefully this explains why that is still a position I hold.

• 40:19Speaker 01

  Looking at the last of a horseman, neurodegenerative disease such as Alzheimer's, something we get asked about a lot, how does that look in terms of what you kind of discussed on cancer, cardiovascular disease as it relates to prevention?

• 40:36Speaker 00

  Well, I would say it's a little bit in the middle. In other words, I think we actually have a slightly better sense of some of the causes, not in all cases, but certainly with Alzheimer's disease, we're getting a much better sense of which people are susceptible, what genes play a role from a genetic susceptibility standpoint. And genes do play a pretty big role there. And we also understand the other factors. And part of the reason for this, Nick, is there's a very simple, but surprisingly accurate adage, which states, what's good for the heart is good for the brain. And study after study after study have demonstrated the

• 41:19Speaker 00

  Every intervention that we take to lower the risk of atherosclerotic cardiovascular disease also reduces the risk of dementia. And that means Alzheimer's disease, vascular dementia, which are the two main ones, but also other forms of dementia. So that means having better metabolic health, having lower APOB, having lower blood pressure, not smoking. Those things dramatically reduce your risk of cardiovascular disease and they dramatically reduce your risk of Alzheimer's disease. Now, an area where dementia has an even bigger positive impact in intervention than cardiovascular disease is with that of exercise.

• 42:03Speaker 00

  So it's no surprise that exercise improves a person's odds of not getting and/or surviving cardiovascular disease, cancer, dementia. But I would say that the evidence for the benefits of exercise are both greater in magnitude and greater in confidence when it comes to the prevention of neurodegenerative disease. So it's interesting because I do think that many people fear dementia more than any other condition and there are very obvious reasons why that would be the case. And it might be that in our practice, we're a bit more optimistic than most based on

• 42:46Speaker 00

  just the nature of what we do and the types of people that are in our practice, meaning like people who really study prevention and really look at these early, early signs of dementia and look at how specific interventions can make a difference. But unfortunately, the flip side of that is that of all the chronic diseases, the dementing and neurodegenerative diseases are the ones for which we have at this time virtually no viable therapeutic options. So the real name of the game with neurodegenerative diseases, specifically the dementing diseases, and the only other one I'll really mention here briefly is Parkinson's disease because it's the most prevalent.

• 43:29Speaker 00

  Movement disorder is that avoiding them is the first, second, and third priority on a list of three priorities. Once we get into treatment land, at least at this point in time, it's not very promising. So these are both diseases where having as higher reserve as you can make a big difference. So the higher your cognitive reserve and the higher your movement reserve, the more resilient you are to the effects of these conditions. I think I should just state the conclusion here that we shouldn't ignore the fourth horseman, which is of course the spectrum of metabolic diseases. As I said, kind of at the outset, I mean, I think along with cardiovascular disease, we really have a pretty clear sense mechanistically of what's driving this.

• 44:13Speaker 00

  I mean, this appears to be primarily a consequence of overnutrition. So energy imbalance is really the driving factor of insulin resistance. And insulin resistance is really the driving factor of the downstream effects that ultimately lead to everything from fatty liver disease, type 2 diabetes. And again, these diseases in their own right are quite harmful and devastating. But the real danger of them is the effect that they're having on the other three horsemen, where they're increasing your risk by 25 to 50%.

• 44:54Speaker 00

  So they really are gasoline on the fire of the other diseases.

• 45:00Speaker 01

  The last kind of foundational question before we get into tactics would be, we just talked so much about prevention and the importance of it, which if anyone who is younger listening, hopefully encourages them to kind of play that longer game. But what about someone who's older? So they just heard you talk about prevention, the importance of it, and they might be thinking to themselves, I wonder if it's too late for me to start thinking about my longevity. What would you say to that?

• 45:31Speaker 00

  Well, I mean, I think there's like the theoretical answer and the practical answer, right? I mean, I think the theoretical answer is, look, while you still have breath in your lungs, it's not too late to do something. But I also think that we're all in a car driving towards the edge of a cliff. It's a lot easier to slow the car down and make sure that you either avoid the cliff altogether, or at a minimum, slow your route to the cliff's edge dramatically if you begin the slowing process before you get there. In other words, everybody understands that when you see a red light, you have to be applying the brakes

• 46:11Speaker 00

  before you reach the actual light. So at some point, I think it is very difficult to back out of a situation. But I also think that that's the rare exception and not the rule. So I've even in the book written about individuals who are in their 70s before they take their first committed step towards health. And these are individuals that in their 80s now are doing better than they were in their 60s from a health perspective, from a movement perspective. So I would absolutely hope that a person listening to us in what might be thought of as their twilight years, who's thinking, man, I wish

• 46:54Speaker 00

  I did something about this sooner. Is it too late? I would say it's not too late. You'll have to make concessions. You need to start slower. You need to make sure you're not getting injured. I mean, there's an entire playbook and we actually have a podcast around this topic specifically around what would an exercise program for the elderly look like. But I definitely would be very disappointed if anyone thought I was communicating that once you reach a certain age, it's sort of all bets are off.

• 47:21Speaker 01

  So moving from health span, lifespan to now the tactics, I think we'll go through each of them, but I think it'd be helpful at the outset if you just kind of list what the five tactics in your quote unquote longevity toolkit are.

• 47:37Speaker 00

  Yeah, I just kind of list things into buckets. I wouldn't say this is collectively exhaustive. There are other things that I think matter that don't warrant a bucket in my view, or maybe I should come up with a sixth bucket that I would put every other thing into, and we could talk about that as well. But the big five buckets are nutrition, exercise, sleep, pharmacology, and emotional health. Again, we could talk about a sixth bucket, which would be pollution, radical temperature exposure, accident avoidance. So behaviors to avoid harmful accidents, automotive accidents, things like that.

• 48:18Speaker 00

  So there's definitely also like a grab bag sixth column that you could include if you wanted to. But I mostly talk about the first five.

• 48:27Speaker 01

  We'll start with your favorite, which is not ironic in that statement. It is actually your favorite, which is exercise. I think what would be helpful is you've talked about this before, but this framework of the centenarian decathlon. Do you want to just quickly state what that is? Because I think it kind of gives some grounding and foundation to how you think about exercise compared to how others may talk about it.

• 48:53Speaker 00

  So there's so much I could say about this. I really thought you were going to throw me a usual ball and start with nutrition, which of course is not my favorite, but we will talk about it. But you're right, exercise is my favorite, and it is my favorite because I think the data are very clear that exercise, if leveraged to its capacity, has a greater impact on your lifespan. Remember, that's the how long you live piece. And your health span, that's the how well you live piece, than any of the others, with the only exception potentially being emotional health. There is clearly going to be the case of the individual whose emotional health is in such ruins

• 49:37Speaker 00

  that until that is addressed, no amount of physical health matters. And in fact, anything else is just prolongation of agony. But if you exclude that. Case, which is, I don't want to minimize that case because I think there are many people who have been in that situation. Exercise really is the king of interventions. So you alluded to something that is one of my favorite topics, which is called the centenarian decathlon. So I realize that some people have read the book and they understand what this means or they've heard me talk about it. But again, the purpose of this podcast, I think, is to make sure that someone who's new maybe gets up to speed on this, or it's a refresher for someone. So the centenarian decathlon is an idea that came to me in the summer of 2018.

• 50:20Speaker 00

  And it's an idea that occurred in an instant, but it was really the result of many years, probably four years of suffering, so to speak. So the suffering started at the end of 2014, when I decided to stop competitively cycling. And not only did I stop cycling, but I was not going to go back to any other sport. So I was not going to be competing anymore in masters, swimming, cycling, obviously had no desire to go back and compete in boxing or martial arts or anything like that. Basically, I was done competing and all I wanted to do was exercise for the sake of exercise. And this, for me at least, was a bizarre, foreign idea.

• 51:05Speaker 00

  Because from the age of 13 until that point in time, which was 41 or 42, I had never trained without a specific purpose. Every single rep, every single lap, every single pedal stroke, everything I ever did was always geared towards a purpose. And now for the first time ever, I was kind of like, huh, what should I do today? I guess I should go for a run. Okay, I guess I'll lift weights tomorrow. I'm in the gym lifting, what am I lifting for? Well, I used to do this, I guess I should still do this. But it was this totally rudderless existence that I had. And it stayed that way until the summer of 2018,

• 51:48Speaker 00

  when I was at the funeral of the parent of one of my best friends. And apologies for repeating this because I do write about this in the book. But basically, at that funeral, I realized that while my friend's mom had died at a relatively old age, I think about 89, her physical life had basically

• 52:12Speaker 00

  Demised so significantly in the past decade that her actual death was almost just a matter of formality. But she had lost the ability to do the things that mattered to her most a decade earlier. So she couldn't play golf anymore because of her shoulder. She couldn't garden because of her knees and hips and back. She couldn't even play with her grandkids. And so she spent most of the last decade of her life largely uninvolved in anything. And did come down with dementia in the final year of her life, and that's what ultimately took her life. But I was just totally blown away by this person that I once remembered as being completely

• 52:56Speaker 00

  vibrant, losing everything and spending this last year in this state. And I realized in that moment, as I literally sat in a church pew, first of all, this is really common. And secondly, this is what I want to train for. For the first time in four years, realized, aha, the thing I want to train for is to avoid this. I want to come up with an event, an athletic event, that will be done at the end of my life and everything between now and then will be training for it. And so I just came up with this idea called the centenarian decathlon, not because it

• 53:40Speaker 00

  implies that one has to live to 100 to compete, or not even to imply that it has to have 10 events, but simply as a mental model to say, what are the most important activities, both activities of daily living and activities of performance that I want to be able to do at the end of my life? And how well can I define them? How well can I understand the physical traits that will be necessary to execute them? And then how much can I reverse from there or backcast from there what I need to be doing today to increase the probability of doing those things tomorrow to the highest level?

• 54:22Speaker 00

  And that has become obviously a huge obsession of mine. As you know, I along with a couple of other folks have started a company around this called 10 squared, which is just geared towards training people to do this. And I think that it is at least until someone shows me a better idea, the best model for how to train if your goal is not something very specific. So again, if you came to me and said, I know how much you love jujitsu. If you're like, look, there's this tournament coming up in six months and I really want to compete for it. That's not the centenarian decathlon. That's a very specific type of training you need to be doing in jujitsu to go and compete there. You know, my wife is running the Boston Marathon

• 55:06Speaker 00

  next year and she wants to run a certain time. She will have nothing to do with training her centenarian decathlon. She is going to be doing very, very specific running workouts to make sure she hits her goals. So there are lots of other ways to train, but my point is that most people aren't training to be the best at their local jujitsu tournament or to run their PR at the Boston Marathon. And even if they do those things, they're usually fleeting. And ultimately, what people really want to be training for is to be the most kick ass versions of themselves in

• 55:45Speaker 00

  the last decade of their life. And again, if that means your 80 to 90 years are functioning like you're a really good 70 year old, that's a totally different experience from what most people go through.

• 55:59Speaker 01

  Let's say someone is training for the centenarian decathlon. So they kind of agree and they say, I want to put all my focus into this, which is how do I become an athlete focused on life? And we don't have to get into these in detail because in the show notes, we'll link to the multiple, multiple places we've talked about them. But what are the four components that you think are important for someone who is interested in training for the centenarian decathlon?

• 56:28Speaker 00

  It starts on the foundation. You have to have stability. You have to have the chassis. Basically, I'd say the chassis and the tires. You have to have every aspect of the motor control, coordination, ability to dissipate force, ability to receive force, ability to balance. There's so much that goes into stability that it, I think, got a full half chapter in the book. And it's far and away the most complicated to explain, but it's really obvious to see it when it's not there. So every one of us is lacking instability, and it was the biggest re-education for me as I pivoted to this way of training. So

• 57:09Speaker 00

  it's everything from learning how to appropriately pressurize your intra-abdominal space to how to unlock your ribs, maintain an appropriate center of gravity, how to be able to isometrically contract muscles as necessary, how to be able to do it under control, how to have good foot mechanics, right? I mean, all of these things we've done dedicated podcasts on because each component of this stability game is quite nuanced. And the good news is while most of us show up to the middle part of our life with enormous deficits, here they're all retrainable. We're actually still quite plastic in our old age. Second component is strength, and I would say a subcomponent of strength is power. So even

• 57:51Speaker 00

  though we lose power very quickly as we age, the more we can maintain it, the better. And you can't have power without strength and stability. The third component, and this is really more of a continuum, the third and fourth are part of a continuum of cardiorespiratory fitness. I talk about this as being a triangle. So the base of the triangle is the aerobic efficiency. So this is the maximum fat oxidation. This is your all-day pace. We want that to be as high as possible. And then the peak of the triangle is the VO2 max. That's most adequately thought of as the engine size. So that's the peak aerobic output. Those are the four components. And one of the exercises we do with both our patients and obviously

• 58:33Speaker 00

  the clients in Ten Square is, once you have a person's centenarian decathlon goals, You break them down into what is required. So if you give me your list, we can take that list and we can say, oh, this requires a VO2 max of 31 milliliters per kilogram per minute. This requires an ability to sit this way, or this requires this much strength in this domain. This requires this type of hip loading, et cetera, et cetera. And then we can evaluate where a person is today and then say, oh, okay. Well, obviously today you can do all of those things, but here's the predicted trajectory of decline on each of those things. And will you be above your benchmarks in 40 years or will you be below them?

• 59:17Speaker 00

  And for most of us, myself included, at least on some of those dimensions, you're actually considerably below them at your target. And therefore you have to raise the performance currently to make sure you hit the targets in the future.

• 59:32Speaker 01

  And like we mentioned, for anyone who is interested in further on anything exercise, in the show notes, we'll link to the multiple podcasts, articles, et cetera, so people can dive in. But moving from exercise to your second favorite, nutrition. What's your framework for how you think about nutrition? Because you don't necessarily think about nutrition as some people talk about it, which is this diet's best or this diet's best. You kind of look at it a little bit of a different way. And so do you want to walk people through your framework and how you assess nutrition and where someone is at in their nutritional state?

• 1:00:08Speaker 00

  Yeah, I mean, I would say that nutrition is a very complicated thing to study. I would say it's the messiest of all the pillars to study, probably even messier than emotional health, although maybe that's debatable. But the reasons for it are obvious and not worth restating. But it's for that reason that there were very few things that can be stated in this field with a high, high degree of certainty. So unfortunately, the challenge in nutrition is you have a lot of people that speak with such insane conviction and they talk about something as though it is.

• 1:00:47Speaker 00

  Absolutely correct, even though if you were putting an error bar on their statement, it would dwarf anything they're saying. And truthfully, I have been guilty of this. And I think 12 years ago, I was talking about nutrition with a level of certainty that I don't think was warranted. And so as the adage goes, the further you get from the shore, the deeper the water. And I think in my older age, I'm actually quite far out from the shore. And I realized the water is awfully deep out here. And there aren't a lot of things that can be stated at a high enough degree of certainty that you should act on them with almost blind faith.

• 1:01:31Speaker 00

  So here are the two that I can tell you with a very, very high degree of certainty. The first is that the single most important input from nutrition to a person's overall health is energy balance. Stated another way, the energy input of food is the first order determinant of health. Maybe stated another way, the total calories you consume would be the most important thing. Not the only thing. I do not want to suggest that a thousand calories of Tic Tacs is the same as a thousand calories of broccoli.

• 1:02:16Speaker 00

  It is not, but I'm also talking about this through the lens of common sense. And the truth of it is, if you subside on a diet of Tic Tacs, you're going to eat a lot more than a thousand calories of them because they're not satiating and they're junk and they're hollow. So I want to be very clear that the primary input is total energy, but it is also impacted by many other things, including diet quality, processing, and macronutrient distribution. The second thing that is abundantly clear is that protein is the macronutrient we should be least flexible on.

• 1:03:00Speaker 00

  Stated another way, we can be quite flexible on how much carbohydrate and fat we consume to fill our energy needs. But because protein is not consumed for the purpose of ATP generation, which is the principal reason we consume carbohydrates and fats, although fats are also essential for some structural purposes, we cannot be too flexible or compromising in our protein requirements. In other words, if you really wanted to just come up with a single number to give people, I would say on average about 1.6 grams of protein per kilogram of body weight should be consumed by everybody.

• 1:03:44Speaker 00

  Now, again, I hate saying that because there's truly nothing that you can say across the board. There are clearly people who, based on what they're eating, will need more protein and there are probably people who can get away with a little bit less. If you took a perfectly high-quality PD-CAS 1.0 protein in a person who's not over-the-moon active, they could probably get away with 1.2 grams or even 1 gram. But, boy, anything below that and you're starting to really miss out. And by the way, as you age, those requirements go up due to anabolic resistance. So, again, we can talk all day about every diet under the sun

• 1:04:24Speaker 00

  and every religion and every faction of every religion around every dietary tribe. But the truth of it is, it's really hard to find a scientist, an actual nutrition scientist. I'm not talking about an influencer. I'm not talking about a health blog. I'm talking about actual people who work in labs doing nutrition, who will disagree with that statement. There are some, but they are in the huge minority. And interestingly, they tend to avoid using human data when they talk about those things. But when you limit yourself to the species of interest, which is humans, not rodents,

• 1:05:05Speaker 00

  and you talk about experimental data coupled with other insights, those two things seem to matter the most. How many calories are you getting? Not too much, not too little. Are you getting enough protein? Obviously, there are other terms. Certainly want to make sure you're getting enough micronutrients as well and that you're avoiding toxins. That tends to be less of an issue today than it was 100 years ago. But of course, that's also really interesting. But a lot of the other stuff, Nick, is details. So when I'm looking at a patient, given how important those things are, to me, it makes sense to be evaluating those things at the outset. So when we do a DEXA scan on somebody on day one,

• 1:05:47Speaker 00

  and we can see how much subcutaneous fat they have, how much visceral fat they have, how much muscle mass they have, and we can do a lot of advanced blood work and see how metabolically healthy they are, how well they dispose of glucose, all these other things. I can very quickly answer three questions, literally on first contact. Are you overnourished or undernourished? And that really comes down to energy balance. How much fat do you have on your body? And how well is it distributed throughout your body? Where is it distributed? Second question, are you adequately muscled or are you under muscled? Third question, are you metabolically healthy or not? And when you can answer those three questions,

• 1:06:31Speaker 00

  which you can in a very short period of time with a relatively small amount of data, that tells you, does this person need to eat more, less, or the same total energy? The same amount of protein or less? And how important and what type of exercise should they be doing to augment our findings? Because we're talking about nutrition, I'll close this out by saying, most people, when they do this, come out slightly in the overnourished category. That's just another way of saying, most people are overweight or obese. I think the numbers are probably 70% of the population are overnourished or significantly overnourished. Therefore, most people, when you go through that whole treatment algorithm,

• 1:07:16Speaker 00

  are going to be in the, I need to eat less camp. If you are in the, I need to eat less camp, you now have three ways to do that, three strategies, if you will. The first is directly reducing caloric intake. So that says, agnostic to what or when I eat, I will simply eat less. This is the most direct way to do it. It has lots of pluses and minuses, which I've discussed in so much detail on other podcasts that we'll link to. The second method is I will identify something or some set of things in the diet that I will remove from the diet. I will restrict them.

• 1:07:59Speaker 00

  This is called dietary restriction. And the more restrictive the elements of your diet, the more effective this technique is. So if you only choose to restrict lettuce, this will have no effect. If you restrict everything but potatoes, meaning if the only thing you allow yourself to eat is potatoes, this will have an enormous effect. So the more you restrict, the better that works. And then the third strategy is time restriction, where you limit the window in which you eat. And the narrower and narrower that window, the greater the likelihood that you will overall induce a caloric deficit. So there's a lot more I can say about nutrition.

• 1:08:40Speaker 00

  We could get into the nuances of which type of fats are better, saturated fats, monounsaturated, polyunsaturated fats. Is a Mediterranean diet more efficacious than a low carb diet? Or a low fat diet? And all of those things, again, I've written about, I've spoken about. But I think from the standpoint of what are the most important things? I think you've got it.

• 1:09:00Speaker 01

  Have you remembered what you ate for lunch yet? That's, I think, the only thing from the nutrition conversation that's missing.

• 1:09:07Speaker 00

  I scarfed down some leftover spaghetti squash that we made yesterday. And what else did I have? Oh, I had a container of blackberries and I had some venison.

• 1:09:19Speaker 01

  There you go. Great. Moving on to sleep. So sleep is something you've written about where you take it much more seriously now than maybe you used to in the past. So do you want to talk about why you think sleep is such an important component of not only lifespan, but also health span?

• 1:09:39Speaker 00

  Well, I think the data really make the case more compellingly than I need to. Fortunately, short-term sleep deprivation is easy to study. And it unequivocally demonstrates a remarkable negative impact on cognition, on physical performance, on physical markers of health, such as insulin resistance, on appetite. Everything that can go wrong in the human body goes wrong when you are sleep deprived. And again, what's nice about this is you don't need to do five-year studies to figure this out. You can do two-week, three-week studies where you take people down to four

• 1:10:20Speaker 00

  hours a night of sleep and you can absolutely destroy them in every physiologic measure during the wakeful period of their lives. So we can then extrapolate from there that, okay, well, if you're only sleeping five and a half or six hours a night, you're probably not getting as much of the negative effects. But when we see and measure other effects that are negative to a lesser extent, it seems pretty easy to attribute them to the reduction of sleep. So in other words, when you look at a person who's not sleeping as inadequately as people are typically studied in short-term studies geared towards identifying

• 1:11:03Speaker 00

  the risks, they get many of the same problems, but just not as extreme, suggesting there's a dose effect to sleep reduction. And truthfully, I think that this is something that I think society is far more willing to entertain today than 10 years ago. I think Matt Walker, who's also a very close personal friend, has had a lot to do with this. Arianna Huffington has brought a lot of attention to this. So I think there are many people out there that are saying, hey, this whole idea of I'll sleep when I'm dead, which used to be my mantra, is like, yeah, you're going to be dead quicker if you adopt that mantra. So you will indeed sleep when you're dead and you'll be dead sooner than you want to be. So again, I think that this one doesn't require a lot of convincing, but how to do it, of course, is a little more

• 1:11:48Speaker 00

  complicated. The good news is there's really a lot of wonderful behavioral tools. And ultimately, for some people, pharmacology or mechanical assistance such as CPAP, if a person has apnea, there are technologies, both pharmacologic and otherwise, that can really help here. But for most people, the behavioral tools do the work. This is really one of those things where very few people need to see a physician to help them sleep or to troubleshoot a sleep. Problem. And when you do, fortunately, there's an entire branch of medicine dedicated to sleep physiology. There are actual physicians who specialize in this and we're certainly not afraid to use them when it's necessary.

• 1:12:32Speaker 00

  There's also a field of behavioral therapy called cognitive behavioral therapy for insomnia. That is an entire discipline that is dedicated towards the cognitive tools that you can use during periods of insomnia. So we always get patients in our practice who just have what can only be described as the most abjectly horrible sleep. And of all the problems we face, this is the one that I tend to be most optimistic about our ability to help in a relatively short period of time.

• 1:13:02Speaker 01

  We have a whole AMA dedicated to sleep along with multiple Matt Walker episodes. So I don't think we needed to get into insane detail because we will link it in the show notes. But you mentioned a few of the behavioral tools. And so if someone says, okay, I need to take more awareness in my sleep. I need to do more to get better sleep. What are some of the things that they can look at and evaluate?

• 1:13:24Speaker 00

  I would say if we were in an elevator and we had only between the first floor and the 15th floor for me to tell you everything that mattered. I would say try to go to bed at the same time and wake up at the same time every day. Give yourself about eight hours to be in bed. Make the room as dark as possible, as cold as possible, and detach yourself from anything stimulating. Especially upsetting, which is work, social media, that kind of stuff for two hours before bed. And if we haven't hit the 15th floor yet, I would say try to not eat or drink any alcohol for three hours before bed. Those would be the no risk, no regret moves to try to fix your sleep.

• 1:14:08Speaker 00

  And that's a lot, by the way. I'm not suggesting that would be easy to do for someone who's doing none of them. But if you gave me a hundred people who were complaining of poor sleep and/or objectively had measurements of poor sleep. And all a hundred of them did that, I think 80 of them would get better.

• 1:14:24Speaker 01

  Moving to drugs and supplements. This is something that if you look at all the different drugs, pharmacologic, if you look at all the supplements, we have an insane amount of content on. Impossible to answer all the questions here that come in. But I think helping people understand just what their relationship with drugs and supplements should be, how they should think about it, how they should not think about it. How do you talk to patients about that who come in to the practice? And maybe have a list of 20 supplements that they show up with?

• 1:14:53Speaker 00

  Yeah, that's definitely one phenotype. I would say just to kind of address both extremes. You have some people who think everything is solved by drugs and supplements. And then you have people who think you should never take a drug or a supplement. And so I just always kind of try to remind people, drugs and supplements are just a tool. To say, I never want to take a drug is kind of like telling a contractor, hey, please do a good job building my house, but just never use the hammer. Or never use the Phillips screwdriver. You can use the Robertson, but not the Phillips. You just want to have tools. We just want to have tools. And the best contractor and carpenter and tradesman is going to have the most tools and the most facility with knowing how and when to use them.

• 1:15:38Speaker 00

  So that said, we do kind of, especially on the supplement side, have a framework. Because as you said, there's a infinite number of supplements. There's a finite number of regulated drugs, but a non-finite number of supplements. So you have to have a framework for this thing. And so the first question I'm always asking myself with any exogenous molecule is, is this a molecule that is being taken to lengthen lifespan or improve health span? You would be amazed at how many times I ask somebody who's taking a supplement, which of those two they're taking it for. Usually you get a very blank stare. I'm taking it because fill in the blank influencer told me to take it. Okay.

• 1:16:22Speaker 00

  So let's say we can establish that you are taking this for one of those reasons. It's either going to make me live longer and/or it's going to improve my physical, cognitive, or emotional health. The next question I would say is, okay, if this is a lifespan enhancer, if this is going to make you live longer, is it doing it by targeting a specific disease? Or is it a broad Gero protective molecule? Similarly, if you're telling me this is a health span enhancer, is it specifically enhancing cognitive health, physical performance, emotional health? Or is it sort of acting through some mechanism we don't understand? I would ask if we have safety data on this.

• 1:17:03Speaker 00

  I would ask if we have efficacy data in humans and/or in animals, if not. And if in animals, how relatable is it? If it's a supplement, I would ask, how can we control for purity? How do we know that what the bottle says is in it is actually what's in it? And that nothing that's not supposed to be in it isn't in it? There are a few more questions, but that's the long and short of it. And so I think one needs to go through that type of exercise and put that type of filter to everything. And then, and only then, I think, should we go down the path of, okay, what supplements do we want to use? Where do we want to turn to pharmacology, hormones, those things?

• 1:17:41Speaker 01

  Moving to the last tactic, and you talked a little bit about this because emotional health fits in the health span bucket as well. But when people think about longevity, emotional health is not something that usually comes up a lot. And so what would you say to someone who maybe is taking the steps in their nutrition, their exercise, their sleep, drugs and supplements, but not necessarily focusing on their emotional health? What would your advice to them be on how emotional health, you don't necessarily correlate it all the time with longevity, but you find it to be an important aspect?

• 1:18:18Speaker 00

  Well, I mean, I think there's two components. I think there is enough evidence, though you could never prove it, that a person who's managing their stress better, who's happier and who has better relationships, probably also lives longer. Certainly, the epidemiology suggests all of that. That's not unclear. But I'm acknowledging that that would be very difficult to demonstrate causality. People could be happier and have better relationships and all those things because their health is better. So it could be reverse causality there. But I think there's actually enough evidence that there's at least bidirectional causality there. But I think to help somebody think about this, I would say, just forget that. Let's pretend that being miserable, lonely, and angry helped you live longer.

• 1:19:03Speaker 00

  And that if you were happy and you had great relationships and you were in harmony, you would live shorter. Who would choose the former when you frame it that way? Outside of extremes, like, okay, happy people can't live past 30, miserable people can live to 100. I'm sure a lot of people would say, well, I'd rather be miserable at 100. But the truth of it is, even framed that way, it seems ridiculous. So all of that is to say, as a thought experiment, just forget the lifespan piece of this. Just think of it through the lens of common sense. Why would you ever choose to be unhappy? It doesn't make sense. And I think what maybe for me was a big insight late in life was,

• 1:19:48Speaker 00

  you can do something about this. Everybody's got a story. Everybody's got a history. Everybody's got a background that brings them to the table, but it's all modifiable. So the software can be modified, is the point. And we've got so much content on this that I obviously couldn't go into it in any detail here. But I think the most important thing for the purpose of this discussion is that this entire area is as important, potentially more important than all of the others. Because without this one in check, the other ones don't matter.

• 1:20:19Speaker 01

  Peter, I think that kind of wraps what we were hoping to cover. And again, As we kind of mentioned on the outset, the idea is not to get into the super intense details on everything. We'll link to that, but more so cover high level longevity 101, how you think about some core aspects for people who are newer, people who need a refresher. I think the last thing that we should end with is just if someone is new and they're listening to this and they maybe feel a little bit overwhelmed on where they should start, right? A lot of information came out of on the lifespan, health span, different diseases, different tactics. What advice would you give someone who is listening? And they would say, I want to take this more seriously, but I'm a little overwhelmed on where to start.

• 1:21:05Speaker 00

  I would say just pick one. It's not a race. And I think finding something that you think you're going to be successful in would be the best first place to start. So if after listening to everything we just talked about, you're kind of like, you know what really resonates with me? My sleep probably sucks. Then I would say, how about you change nothing in your nutrition, nothing in your exercise. Don't do anything else. Don't buy a supplement. Just work on implementing the stuff we talked about on sleep. Because if you get that better, it's going to do two things. It's going to make it easier for you to address the other things. And it's going to give you the confidence and agency that says, hey, I actually have control over this thing. It's not out of my hands.

• 1:21:50Speaker 01

  Awesome. Well, Peter, hopefully people enjoyed this special episode, but thank you for your time and we'll see you on the next one.

• 1:21:57Speaker 00

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