The Peter Attia Drive - #311 ‒ Longevity 101： a foundational guide to Peter's frameworks for longevity, and understanding CVD, cancer, neurodegenerative disease, nutrition, exercise, sleep, and more

00:00:00.000 Hey, everyone. Welcome to the Drive podcast. I'm your host, Peter Atiyah. This podcast,

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00:01:04.440 Welcome to a special episode of the Drive. For today's episode, we're going to do something a

00:01:08.600 little bit different. This is an episode that kind of reads more like an AMA, where I'll be

00:01:12.560 answering a set of questions, but it's going to be available to everyone, not just to our subscribers.

00:01:16.700 Typically, of course, our episodes are really kind of deep dive conversations. That's what we're really

00:01:20.900 known for, but we also get a lot of questions from maybe people who haven't been listening for long

00:01:26.320 asking something akin to, hey, where do I begin? Today's conversation is really intended to serve

00:01:32.720 as a starting point. It's also a great thing that you can have if you have a friend who you're trying

00:01:37.640 to introduce to these topics and you want to get them kind of up to speed. This is a great sort of

00:01:42.220 longevity 101, as it were. We kind of lay the foundation for how I think about this, the structure

00:01:49.540 that I apply to longevity, explain the various concepts of lifespan, healthspan, the four

00:01:55.300 horsemen of death, the marginal decade. We talk a little bit about the tactics. We talk about these

00:01:59.940 five things of exercise, nutrition, sleep, drugs, and supplements, emotional health. And since this

00:02:04.800 is obviously based on the scope, a rather superficial treatment of these concepts, the show notes are

00:02:10.240 going to be quite detailed and will actually point you in the deeper direction of anything that is

00:02:15.880 covered. So again, if you're feeling overwhelmed about some of our content, we really hope that

00:02:22.020 this is an episode that's going to help give some of the foundational information that allows you to

00:02:27.020 then appreciate some of the deeper dives that we are more commonly doing. So without further delay,

00:02:31.680 I hope you enjoy this special episode of The Drive.

00:02:39.420 Peter, welcome to a special episode. How are you doing?

00:02:41.840 Great.

00:02:42.140 Awesome. Well, for today's episode, we're going to do something a little different.

00:02:46.380 One thing we know and we can hear from people is if you look at podcasts, sometimes podcasts aren't

00:02:51.620 the best way to learn about information. And part of that is because each week we cover a different

00:02:56.020 topic in different detail, and it may be cancer one week, exercise the next week, Alzheimer's,

00:03:01.520 whatever it may be. And we go into different levels of detail. And so we also know we have newer

00:03:07.260 people who are listening and sometimes they can be a little overwhelmed by all the different things.

00:03:11.640 And so what we wanted to do was record an episode, which is basically longevity one Oh one. And so

00:03:17.940 we're just going to go through core lifespan, health span, each of the tactics and just touch

00:03:24.240 on the core frameworks to give people kind of a foundation of how they can think about their own

00:03:30.480 longevity and also how they can think about when they listen to the podcast, how these different

00:03:34.760 pieces fit together. And so if you've listened since episode one, you might not need to listen

00:03:41.240 to this one, but it might be one you share with someone to be like, Hey, this is what this guy talks

00:03:46.520 about. So we're going to hit all the five tactics, some real basic questions, but it should be pretty

00:03:53.780 simple, pretty high level. So with that said, anything you want to add before we get into it?

00:03:59.680 I mean, simple and high level aren't typically words I associate with very well. So I'm a little

00:04:06.840 gun shy about how we do this, but let's give it a shot.

00:04:10.300 So you're saying the first question that I should ask is what did you eat today for lunch and why

00:04:16.700 should everyone eat that for lunch every day as well?

00:04:19.740 Absolutely. That would be a great question.

00:04:21.980 Perfect.

00:04:22.300 I think I've already forgotten what I, no, no, I remember what I had.

00:04:25.560 I remember.

00:04:26.320 All right. We'll save that for the nutrition section, but starting off with just a few

00:04:30.400 foundational level questions. The first being, how do you even define this word longevity?

00:04:35.700 It's a word that gets thrown around a lot, means different things to different people.

00:04:40.180 I think it'd be nice just to be like for this conversation to anchor what we're talking about.

00:04:44.940 How do you define longevity?

00:04:46.080 I don't make an argument that my definition is the best definition, but I agree with the

00:04:51.560 idea that whenever someone is talking about it, it's worth asking them what they mean by it.

00:04:57.860 And it's also why I tend to bristle at the association with longevity, because if someone

00:05:03.760 says, oh, are you a longevity doctor or something like that? I have no idea if they know what longevity

00:05:09.500 means according to my definition, which again is not to say it's the right definition, but it's

00:05:13.600 the lens through which I think about it. And therefore everything I talk about, any question

00:05:18.380 I answer will be through the lens. So the way I think about it, and I suspect the way some others

00:05:22.200 do as well, is that longevity is, well, it's a function. So again, I tend to think of things

00:05:28.880 mathematically made up of two vectors. And one of these vectors is lifespan. And one of these vectors

00:05:34.980 is health span. And both of these vectors are necessary to demonstrate the function of longevity.

00:05:43.600 Now, one of these vectors is much easier to understand because it is discrete, it is binary,

00:05:51.640 and it is objective. And that is the lifespan vector. So there are some edge cases, but for the

00:05:58.660 most part, you are alive or you are dead. And we think of that through the lens of death certificate

00:06:06.500 death. Again, we could talk about an edge case. You can have an individual who is brain dead,

00:06:12.020 but who is being kept alive. And we could debate whether that person is dead or alive. But I think

00:06:17.520 for most people, there's very little confusion about what it means to be alive or dead. And notice

00:06:23.860 that lifespan says nothing about the quality of a person's life. We'll save that for a second.

00:06:29.000 But in a nutshell, that is lifespan. It is to be respiring or not to be respiring. And it is,

00:06:34.360 again, one of the vectors of longevity. So in as much as we want to increase longevity,

00:06:40.260 we presumably want to have something to do with increasing lifespan. The second vector that makes

00:06:46.740 up this longevity function is the health span vector. This is far more complicated to explain.

00:06:54.280 It is far more subjective. It is analog as opposed to digital, meaning it is not discrete on off.

00:07:02.860 It is variable. And it also has three components in the way that I think about it. So one of those is

00:07:12.120 a physical component. One of them is a cognitive component. And one of those is an emotional component.

00:07:18.900 Now, in the first version of Outlive, when I wrote it, or maybe it was the second version, but not the

00:07:26.220 version that got published, I went to great lengths to describe that the cardiorespiratory death, the

00:07:33.860 I'm not respiring death certificate death as type one death. And then I went into great machinations to

00:07:40.060 talk about the three types of decline in health span as physical, cognitive, and emotional death.

00:07:48.420 And I think for probably good reason, everybody, the publisher and bill, everybody really pushed back

00:07:54.480 on that. And they thought it was a little too morbid to talk about physical death as the death of your

00:08:00.820 exoskeleton and cognitive decline. And I think they were right. I think that death was probably too strong

00:08:05.820 a word there. But my point was that all of those things can be robbed of a person. And even though

00:08:12.880 they're still technically alive, their quality of life has been sapped. So let's not think of it that

00:08:18.700 way. Let's think of it as you have these three sub vectors of the vector health span. And each of

00:08:26.060 those, there are ways that we can try to quantify them. But ultimately, I think people will have their

00:08:31.200 own subjective assessment of what it means to be physically healthy, or what it means to be

00:08:35.420 cognitively healthy, or what it means to be emotionally healthy. I think another thing that's worth

00:08:39.520 pointing out here is that two of those three inevitably decline with age. So the physical

00:08:47.080 component of health span, which I'll define in some detail in a moment, and the cognitive component

00:08:52.880 of health span, they very predictably decline with age. Now, that doesn't mean that everybody's

00:08:57.380 declined at the same rate. And that doesn't mean that for everybody, the decline reaches a level

00:09:03.460 that is, quote unquote, pathological. But it simply means, and I was thinking about this today in the

00:09:09.120 gym, actually, I was like, wow, it is really so obvious to me with each passing day that I am

00:09:14.440 completely past my prime physically and cognitively. And I will never again be as physically strong,

00:09:24.660 fit, flexible, free of pain, like pick your metrics that all make up physical health span. I will never

00:09:30.840 again reach the pinnacles that I had reached in my late teens and 20s. And similarly, cognitively,

00:09:37.800 I'm basically a moron compared to the person I used to be in terms of processing speed, problem 0.99

00:09:44.480 solving, just raw intellectual horsepower. Those things are going to decline even further. Now, 0.99

00:09:50.780 there is more nuance to this, because there are certain things physically today that I think I

00:09:55.900 actually do better than I did before. In other words, you take advantage of the fact that as you're

00:10:00.860 getting less explosive, less powerful, well, you can still kind of maintain strength. And if you learn

00:10:07.800 more intelligently, you can actually become more effective. And similarly, as our intelligence

00:10:13.980 transitions from a more fluid form when we're young to a more crystallized experiential form when

00:10:20.840 we're older, we still have remarkable ability to contribute. But there's no denying that on some of

00:10:28.340 the prime levers against which you would evaluate these, we're in a state of decline. Conversely,

00:10:34.060 the third part of health span, which is emotional health, it actually doesn't really tie to age much

00:10:41.300 at all. Depending on how you evaluate it, it almost seems to have a U-shaped curve, not a really big

00:10:48.020 obvious U, but kind of a dip in, I think statistically, probably the late 40s, and then a gradual rising

00:10:54.820 again. So one of the things that I always try to remind myself and then remind my patients is,

00:11:01.020 this is something we can really look forward to provided we do the work. I can be emotionally

00:11:06.220 better off in a decade than I am today. And I am certainly better off today than I was a decade ago.

00:11:12.980 So I would say that that is at the highest level, how I describe longevity. And therefore,

00:11:19.880 when a patient comes to me and says, I'm interested in longevity, I want to make sure that what they're

00:11:26.300 interested in is what I understand. Because there are many other definitions of longevity out there.

00:11:32.080 And if your definition of longevity is, I want to live to be 200, I wouldn't obviously be able to

00:11:36.780 help you. So the way I think about it is longevity means how do we live longer? I think that means

00:11:43.640 years longer, a decade longer, it doesn't mean a doubling of lifespan. And how do we reduce the rate

00:11:49.700 decline of decline of health span? That would probably be the most operative way to talk about

00:11:54.780 it. So that's obviously very verbose. And that's why I think it's not something that you explain very

00:12:02.700 quickly to somebody. But given that that's the purpose of what we're talking about today, I think

00:12:07.020 it's probably worth going into that detail. To double click on that, because you kind of at the

00:12:11.140 end there mentioned where I feel like a lot of times when longevity and that word gets thrown around,

00:12:15.880 it is on the how long you live side. So I think it's worth double clicking. Why do you think it's

00:12:22.280 so important for someone to not only care about how long they live, the lifespan side, but also the

00:12:29.520 health span side that you said there and also how well they live? There are several reasons for this to

00:12:35.160 be relevant. First, you can think of this kind of at the level of a thought experiment. So in the book,

00:12:42.700 I write about the Greek god Tithonus and how he wished for immortality, he was of course granted

00:12:50.380 his wish, but because he had forgot to ask for eternal youth, he became this indefinitely suffering

00:12:58.760 human being who continued to age in perpetuity while his body declined. So just sort of theoretically,

00:13:06.380 I think anybody who thinks about it for long enough would realize that any desire to live longer

00:13:12.540 has to be accompanied by a desire to preserve health span. I believe that anybody who thinks

00:13:17.740 they want to live to be 200 implicit within that, I hope is the desire to function as someone who is

00:13:25.360 much younger. If a person says to me, I want to live to be 95. Well, I'm assuming, and if not,

00:13:33.560 we'll tease this out. I'm assuming they don't want to look like most 95 year olds. What I assume is I

00:13:39.220 want to live to be 95, but I would hope that in the final years of my life, I function like a 75 year

00:13:45.200 old, a healthy 75 year old. So that's why I think the second thing here is, and the reason, at least

00:13:51.820 for me, that health span is such an important focus. We're going to talk, I'm sure about medicine 2.0

00:13:58.020 versus medicine 3.0, but one of the most important concepts within medicine 3.0 is an equal obsession

00:14:07.320 with health span as lifespan. And again, health span by itself is valuable. At any given age,

00:14:15.700 whether it's 40, 50, 70, or 80, to, for your age, have a better physical body, a better cognitive mind,

00:14:25.120 better emotional health, always exceeds being below it. It's so self-evident, it doesn't require stating it.

00:14:31.340 Secondly, all the things that you do to improve your health span are twofers. Anybody who works for

00:14:39.600 me knows what a twofer is, and a threefer, and a fourfer, and how much I hate onefers. So a twofer

00:14:45.820 means you're getting a two for the price of one. So when you do all those things to improve your

00:14:52.300 health span, you are also improving your lifespan. You could make a case that most of the benefits

00:14:59.320 benefits in lifespan. Roughly, I would say three quarters of the benefits you can get towards a

00:15:07.100 longer life come solely from pursuing better health. I want to say that again because I think it

00:15:13.460 is, for me at least, it's such a profound statement. If you never thought once about trying to live a

00:15:20.180 longer life and focused relentlessly on how can I improve my strength, my endurance, my stamina,

00:15:28.180 and again, all the nuance around these things, my balance, my coordination, my processing speed,

00:15:34.680 my working memory, my emotional health, my happiness, my relationships, if you only focused

00:15:40.020 on those things and never once thought about heart disease, cancer, Alzheimer's disease specifically,

00:15:46.840 I still believe you would capture three quarters of the way towards optimizing your lifespan.

00:15:54.600 I think it's a bold statement. I can't confirm that that's exactly correct. That's not a studyable

00:16:00.100 question. But my conviction is quite strong that pursuit of health span is valuable in its own right,

00:16:07.020 even if it didn't lengthen life at all. And the fact is, it probably does. And it probably does to

00:16:13.160 a greater effect than all of the efforts that largely medicine 2.0 puts directly into lifespan extension.

00:16:20.340 You hinted at it there. And so I think it's worth just going into it. You've written about it too,

00:16:24.920 but do you want to talk real quick about medicine 1.0, 2.0, 3.0?

00:16:30.420 Yep. So medicine 1.0 is the type of medicine that dominated for virtually all of human existence. So

00:16:36.920 if we argue that humans have been around, homo sapiens have been around about 250,000 years,

00:16:42.000 from the arrival of our species until the latter part of the 19th century, we were practicing this

00:16:50.320 thing called medicine 1.0, which truthfully wasn't medicine in the way that we think about it today.

00:16:55.540 It wasn't scientific in the way that we understand science today. It was the best that humans could do

00:17:03.340 missing this tool, missing this tool of inference and relied on a belief about perhaps gods, spirits,

00:17:13.740 humors. And, you know, it to be just blunt was largely ineffective. And so the doctor of the past

00:17:20.600 didn't have any tools in large part because they didn't have any understanding of what was going on

00:17:25.740 in terms of disease processes. So not surprisingly, humans didn't live that long on average, and the

00:17:32.900 median life expectancy would have been into the late 30s or early 40s. The causes of death were

00:17:39.080 typically related to communicable diseases, infections, and death associated with child mortality

00:17:47.940 and maternal mortality. So just the process of having a baby was incredibly dangerous to both the

00:17:54.980 mother and the baby. And obviously that heavily skews lifespan data. If you're killing young mothers 0.76

00:18:01.680 and babies in the process of having babies, you're really bringing down lifespan and life expectancy

00:18:06.960 and couple that with infections, communicable diseases, and trauma. And I think most people aren't

00:18:12.180 surprised to know that, yep, that's pretty much how people died. And then, of course, after the Civil

00:18:16.500 War and we move into the latter part of the 19th century, a couple of things start to come together.

00:18:21.320 Now, the first of these actually happened in the 17th century, but it wouldn't become germane to

00:18:28.560 medicine until 300 years later, 200 years later, rather. And that was Francis Bacon codifying the

00:18:36.680 scientific method. So again, this is something we take for granted today, but this idea that you would

00:18:43.680 make an observation, which is what science is all about, you observe something around you, you observe

00:18:49.580 something in the natural world, you form a hypothesis about why it is happening, you design an experiment

00:18:57.700 that is equipped to test the hypothesis, you conduct the experiment and measure the outcome, and you

00:19:05.960 compare the results of the experiment to the prediction of the hypothesis. And that is effectively the

00:19:12.260 framework for what science is. And so with that as the scaffolding upon which people could begin to make

00:19:22.260 inference, you now layer on some other remarkable discoveries and insights. So a creation of the light

00:19:30.180 microscope, the advent of germ theory, and ultimately the development of antimicrobial agents.

00:19:38.200 All of these things collectively, I think I would add to that just the practice of sanitation led to a

00:19:45.560 remarkable change in the trajectory of human lifespan. And of course, it's so remarkable that if you go

00:19:51.760 from the late 1800s until, you know, fast forward just 100 years, which again is a sliver of time

00:19:59.280 across a 250,000 year timeline, human lifespan approximately doubled. Three, four, five generations to

00:20:07.760 double human lifespan that had previously been unchanged for hundreds of generations is a remarkable feat. And we

00:20:15.420 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

00:20:23.960 ultimately developed even more remarkable statistical tools that allowed for things called randomized

00:20:30.680 controlled experiments or RCTs, randomized controlled trials. And this really allowed Medicine 2.0 to

00:20:38.680 flourish and become supercharged. And obviously, for the most part, Medicine 1.0 was completely displaced by

00:20:46.580 this. Now that doesn't mean that there aren't still some quacks out there that practice witchcraft, 1.00

00:20:50.400 but for the most part, when a person has an infection, when a person has congestive heart

00:20:58.900 failure, when a person is in renal failure, when a person has appendicitis and needs to have their

00:21:05.520 appendix removed, when a woman has a complicated pregnancy, all of these things now for people who

00:21:11.740 are in the developed world are really easy things to manage using the toolkit of Medicine 2.0. So again,

00:21:19.040 Medicine 2.0 was and remains an enormous success. And I certainly wouldn't be sitting here talking

00:21:27.520 without Medicine 2.0. I would likely have been dead already, as would you have. So why do we need to go

00:21:34.560 any further? Why do we need a Medicine 3.0? Well, for all of the successes of Medicine 2.0, it has indeed

00:21:42.620 had a couple of obvious and notable failures. The most obvious is that lifespan has largely faltered.

00:21:50.900 So there really has not been any extension of lifespan beyond that which came from the eradication

00:21:59.140 of the conditions that led to the demise of most people between the Civil War and the end of the

00:22:05.040 First World War. In particular, the types of diseases that kill people today are very different

00:22:11.780 types of diseases from those that killed people 150 years ago. So the leading causes of death,

00:22:18.720 which I describe as the four horsemen of death, are the diseases of atherosclerosis. So coronary

00:22:25.100 artery disease and cerebrovascular disease, cancer, the neurodegenerative diseases and dementing

00:22:31.240 diseases. So Alzheimer's disease, Parkinson's disease, Lewy body dementia, vascular dementia,

00:22:37.080 frontotemporal dementia, all of those diseases. And then the slew of metabolic diseases that while

00:22:42.540 directly not responsible for an enormous number of lives lost compared to the other categories,

00:22:49.160 indirectly contribute immensely by amplifying all of these. Now there's a couple of other things I

00:22:55.260 haven't mentioned there at the population level. Chronic obstructive pulmonary disease is also an

00:23:00.120 enormous cause of death, but its cause is almost exclusively related to cigarette smoking.

00:23:05.180 So I don't really hold medicine 2.0 particularly responsible for the failure of mitigating that.

00:23:11.840 That's really more of a public health question. If people don't smoke, they don't get COPD,

00:23:17.040 even though COPD is one of the leading causes of death. There are, of course, accidental deaths,

00:23:22.720 and we can spend some time talking about those later because there's an enormous spread of what those

00:23:28.780 look like across lifespan and, of course, by geography. In essence, the purpose of medicine 3.0

00:23:35.160 is to try to address where medicine 2.0 has fallen short. It's not to replace medicine 2.0. I certainly,

00:23:43.540 from time to time, hear feedback from people who I think misunderstand the arguments I've tried to

00:23:50.100 lay out. And there's nowhere that I'm suggesting that we need to do away with medicine 2.0, that we

00:23:56.140 don't want the system as it exists today in its capacity to do what it can do. What I argue is that

00:24:02.820 we need to shift resources away from solely focusing on medicine 2.0 to focusing on what

00:24:09.060 we'll talk about in a minute, which is medicine 3.0. So if we're putting 100 units of resources

00:24:13.960 today into medicine 2.0, I think most economists would argue that's still too many units of economic

00:24:20.420 input. In other words, healthcare makes up far too big a section of the economy. So maybe instead of

00:24:27.980 it being 100 units that go into healthcare, it really ought to be closer to 60 units that go

00:24:33.480 into healthcare. And I would argue further, maybe 30 of those units should be aimed towards medicine

00:24:40.380 3.0 and 30 of those units should be aimed towards medicine 2.0. Because when it hits the fan and

00:24:47.800 something goes really wrong, trauma, infection, heart attack, by all means, you want medicine 2.0 there

00:24:55.180 to backstop those things. But medicine 3.0's job is to make those encounters with medicine 2.0 less

00:25:03.540 frequent, less severe, and later in life. That is effectively the difference. The final point I'll

00:25:09.620 make on that is kind of just briefly explaining what medicine 3.0 is, which is, because at this point,

00:25:14.140 it's self-evident. It almost doesn't need to be explained. Medicine 3.0 really has two main hallmarks.

00:25:19.920 The first is that it is aimed at preventing rather than treating chronic disease by acting early,

00:25:29.860 acting aggressively, and tailoring the therapies to the individuals based on the best available evidence,

00:25:39.040 which is not necessarily going to be derivable from randomized control trials.

00:25:44.220 And the second pillar of medicine 3.0 is that healthspan is to be given at least as much effort

00:25:53.500 and attention as lifespan. This is, again, another enormous difference between medicine 2.0 and

00:25:59.920 medicine 3.0. Medicine 2.0 does not place emphasis on healthspan. Its emphasis on healthspan is anywhere

00:26:07.920 from zero to very small, depending on the subspecialty. So there are certainly some

00:26:13.320 physicians whose practices do take them a little bit into the arena of healthspan. But outside of,

00:26:20.580 for example, physicians or healthcare providers who work specifically in the arena of mental health,

00:26:26.120 again, it's relatively low. Obviously, orthopedic surgery is a discipline of medicine that is more

00:26:32.400 squarely featured in the healthspan arena. But for the most part, most of the healthcare dollars

00:26:38.780 are spent on addressing and trying to elongate lifespan. And I would argue that we need to be

00:26:45.360 putting just as much effort into healthspan. That's the fundamental difference between medicine 3.0,

00:26:50.660 2.0, and 1.0.

00:26:52.300 To double click on the four horsemen just a little bit, you mentioned what those four are,

00:26:56.680 but do you also want to talk a little bit about, for each of them, what we know in terms of

00:27:02.500 prevention? So if medicine 3.0, prevention is really important, how do you think about

00:27:08.420 our knowledge of those diseases as it relates to someone who is trying to live as long as possible?

00:27:16.600 Sure. We'll take them from the top. So the atherosclerotic diseases, along with the fourth

00:27:22.840 horsemen, which is the metabolic diseases, are probably the two that we have the most insight

00:27:27.940 into as far as what are the pathophysiologic drivers. And therefore, we either theoretically

00:27:35.260 or in some cases practically also have, I think, the best insight into how to prevent them.

00:27:40.720 So ASCVD is a disease that has both a genetic component and an environmental component. But it

00:27:49.080 really doesn't have much of a component of luck, as far as we can tell. So stochastic processes

00:27:54.440 involving mutations doesn't seem to play a role. There's just pure causality from the standpoint of

00:28:01.180 environmental triggers and from genetic inheritance. So both of those factors play through three

00:28:10.620 pathways, all of which are important. So first is a lipoprotein pathway. Second is an endothelial

00:28:18.740 pathway. And third is an inflammatory pathway. But I realize as I'm saying that it doesn't make a lot

00:28:25.540 of sense. So I'm going to try to step back and put this into English. The three things that have to

00:28:30.600 happen for atherosclerotic disease are as follows. The first is a molecule called a lipoprotein,

00:28:38.060 which carries cholesterol through the body. And it's specifically a lipoprotein that has an

00:28:43.480 ApoB protein on it because there are lipoproteins that don't have ApoBs on them. And we don't have

00:28:49.440 to worry about those. But the lipoproteins that have ApoBs on them can enter the artery wall when

00:28:58.260 the endothelium is intact. But they do so more prevalently and more easily when the endothelium

00:29:05.700 is damaged. The endothelium is simply the lining of cells on the innermost membrane. I mean,

00:29:12.620 closest to the artery or outermost from the standpoint of the artery wall, the one that is

00:29:16.260 most in contact with the circulation. If those ApoB-wrapped lipoproteins get trapped inside the

00:29:24.500 endothelial layer, a chemical process known as oxidation takes place. And that leads to inflammation.

00:29:32.760 What that means is the body thinks something is wrong and I need to fight it. Just as when you get

00:29:38.980 an infection, a healthy immune system detects the inflammation caused by the microbial agent and it

00:29:46.800 sends the troops there to get rid of it. But in this case, the insult does not come from an infection.

00:29:54.240 It comes from the oxidation of the cholesterol contained within the ApoB particle as it sits in

00:30:01.580 the endothelium. And that process initiates a devastating cascade of events that ultimately

00:30:10.220 can create so much damage in the wall of the artery that it can lead to a rupture of the plaque,

00:30:18.300 which is the repairing process. The rupture of that plaque acutely leads to blood loss and ultimately

00:30:25.840 oxygen loss to the muscles of the heart beyond the point of that blockage. That process is known as

00:30:32.980 a heart attack and about 50% of the time it is fatal the first time a person has one. So if you want to

00:30:40.900 think about preventing cardiovascular disease, ischemic cardiovascular disease, you have to have

00:30:47.600 an insight into all of those things. You have to be thinking about how do I have fewer ApoB particles

00:30:56.100 because the more of those particles you have, the more of them that are going to enter the endothelial

00:31:02.180 space. The data on this is as unambiguous as any data are in medicine from clinical trials, epidemiologic

00:31:11.920 trials, and Mendelian randomization. In other words, you have the only three layers of evidence you can

00:31:18.260 ever look to, experimental data, MR, and clinical epi, and they all say the same thing. There is a log

00:31:28.520 linear reduction in ASCVD as ApoB goes down. The second thing you have to do is you have to protect your

00:31:37.260 endothelium. So anything that aggravates and weakens and makes the endothelium more vulnerable

00:31:44.660 to penetration by ApoB is problematic. And the most common factors that we think are doing that

00:31:51.760 are smoking, blood pressure, and very likely the metabolic conditions that cluster with insulin

00:32:00.840 resistance, hyperinsulinemia, and type 2 diabetes. So some combination of elevated glucose, elevated

00:32:08.340 insulin, and other metabolic byproducts such as homocysteine, uric acid, all of these things serve

00:32:15.100 to weaken the endothelium along with elevated blood pressure and smoking, and that creates a greater

00:32:21.940 susceptibility. Again, it's not surprising that all of those things pose about an equal risk to

00:32:28.060 cardiovascular disease, as does the presence of elevated ApoB. And then the third piece of the

00:32:33.700 puzzle, and the one for which we really don't do much directly in the way of treatment, is the higher

00:32:39.720 the inflammation, the more likely the higher this is going to be. And the reason this is probably

00:32:45.160 lesser of the three is, with very rare exceptions, is it a direct therapeutic tool. In other words, we

00:32:53.560 clearly therapeutically address the first two. We therapeutically lower ApoB. We manage blood

00:33:01.420 pressure. We tell people to not smoke, which of course is a therapy. We use exercise and nutrition

00:33:06.020 to manage metabolic health and even pharmacology. But directly from a pharmacologic standpoint, we don't

00:33:11.280 really manage inflammation. We can. There are a couple of agents that are used, somewhat not impressively,

00:33:16.700 and maybe somewhat on the margins impressively. But most of the evidence around reducing inflammation

00:33:22.360 probably comes from doing things much more broadly around nutrition, sleep, and exercise that we've

00:33:29.520 talked about elsewhere. So in a nutshell, that's really what it comes down to. And it's for that reason

00:33:35.460 that I'm often making a very bold statement, which is even though cardiovascular disease is the leading

00:33:42.580 cause of death in men, in women, in the United States, but also in the world, it doesn't need to

00:33:49.640 be. It really, really doesn't need to be. And it is a very bizarre tragedy that 19 million people a year

00:33:57.300 still die from cardiovascular disease, given how much we know about what causes it and how many tools

00:34:04.780 we have to prevent it. You kind of mentioned the first, second horseman there. How do you think

00:34:10.380 about prevention for the others, which is neurodegenerative diseases and cancers?

00:34:16.060 Let's take them in order. So cancer would be the next most deadly of the horsemen. And here is one

00:34:22.140 where a lot of what I said with respect to heart disease is actually quite different. In heart disease,

00:34:28.720 we really have a pretty clear sense of what the genetics look like. So there are a handful of

00:34:33.260 genetic things like familial hypercholesterolemia, which is a very, very heterogeneous condition that raises

00:34:39.760 apolipoprotein B, LP little a, which we'll save for another time. We've got lots of content on that.

00:34:46.140 But when it comes to cancer, we know that, boy, there are some really clear and obvious genetic

00:34:52.960 drivers of cancer. Like there are a handful of genes, some that many people have heard of, such as

00:34:58.720 BRCA1 or BRCA2, which are heavily associated with breast cancer, or Lynch syndrome, which would be

00:35:06.180 heavily associated with colon cancer and other types of cancer. But for the most part, when we say that

00:35:15.320 cancer runs in a person's family, we still aren't really even able to identify the genes through which

00:35:21.620 this is transmitted. It appears to be very polygenic. Furthermore, while we know of at least two

00:35:28.660 significant environmental triggers for cancer, smoking and obesity, and I'll say more about obesity in a

00:35:36.800 second, we actually have very little to say about many other triggers. Despite what people would have

00:35:42.840 you believe, we have very little insight about if at all foods, specific foods at isocaloric amounts. So we

00:35:51.380 can talk about an abundance of food because that factors into the obesity trigger. But if we're talking about

00:35:56.440 a bunch of people eating an isocaloric energy-balanced diet, again, despite all of the propaganda around

00:36:04.840 this, oh, red meat this or soy that or whatever, there's actually just the scantest of evidence to

00:36:10.980 suggest that any of these are promoting cancer in the slightest way. So when you take all of this

00:36:18.300 together, what you realize is that, okay, smoking is clearly driving cancer. Obesity is clearly driving

00:36:25.100 cancer. Not all cancers, but many cancers. About two-thirds of cancers have a very strong

00:36:31.380 tie to obesity. I think if you look under the hood of that, you'll realize it's probably not the

00:36:37.520 excess fat per se or the adiposity that's driving cancer, and rather it's the growth factors that are

00:36:46.060 doing it. So obesity comes with more inflammation, comes with more growth factors such as insulin and IGF,

00:36:53.280 and it seems more likely that those are the things that are actually leading the increase

00:36:58.920 in cancer. But that leaves a bit of a vacancy in terms of what else explains it. And this is where

00:37:06.100 a scientist like Bert Vogelstein and others would suggest that, look, there's actually just a component

00:37:11.320 of really bad luck here. There are mutations that occur. Every cancer begins with a mutation,

00:37:18.520 and most of those are somatic mutations. That means that most of those are mutations that occur

00:37:25.080 in cells that were developed normally. So these are your germline, the cells you inherited. These

00:37:32.240 were normal cells, but then mutations were acquired. And mutations fall into one of two categories.

00:37:39.000 These are either mutations that are tumor-promoting, so oncogenic mutations, or they are mutations of

00:37:49.160 tumor suppression. So we have genes that are set out to suppress cancer, and if you get a mutation in

00:37:55.860 one of those, the body loses the ability to suppress cancer. And then we get mutations in genes that turn

00:38:03.120 cancer on. And again, a number of these are inherited, but many of them, most of them are acquired. And

00:38:11.320 the what is vexing us still. And again, I think the best working hypothesis is that bad luck plays a lot

00:38:20.100 of role in that. Now, it would be a topic for an entirely different podcast to look at other things that

00:38:25.440 may be triggering those mutations. Again, in some cases, we know that viruses play a role in those

00:38:30.860 mutations. But what I'm really talking about is where do the majority of these come from? That's an

00:38:36.400 area of huge interest. And the other problem with cancer that also is not afforded to cardiovascular

00:38:43.040 disease is the treatment options are less effective. So a person today who has advanced cardiovascular

00:38:52.120 disease has a much better prognosis than a person today who has very advanced cancer. A person today

00:38:59.300 with stage 4, i.e. metastatic, endothelial tumors, so that means a solid organ tumor like breast,

00:39:09.380 lung, pancreas, prostate, colon, one of the quote-unquote bread-and-butter tumors, a person

00:39:16.700 today who has one of those cancers that has spread from its original site to a distant site, that's

00:39:22.380 metastatic or stage 4 cancer, that person has about the same 10-year survival as a person did with

00:39:29.160 that tumor 50 years ago. They have a much longer median survival. They will live longer. They might

00:39:35.620 live for five years instead of one year, and that's nothing to sneeze at. But they're not cured at any

00:39:41.740 higher a rate. And obviously, that's a discouraging statistic. So as we think about cancer, we obviously

00:39:48.080 think the first and most important thing is to do everything you can to avoid getting it. But as I

00:39:53.480 alluded to, that playbook is not as thick as the don't get heart disease playbook. And that leads to

00:40:00.900 a very controversial thing that I talk about, which is the importance of early and aggressive

00:40:06.760 screening. And again, we don't have to go into that now. We've already devoted tons of content

00:40:11.180 to the arguments for and against that approach. But hopefully this explains why that is still a

00:40:18.200 position I hold. Looking at the last of the horsemen, neurodegenerative disease, such as Alzheimer's,

00:40:25.200 something we get asked about a lot. How does that look in terms of what you've kind of discussed

00:40:31.440 on cancer, cardiovascular disease, as it relates to prevention? Well, I would say it's a little bit in

00:40:37.980 the middle. In other words, I think we actually have a slightly better sense of some of the causes,

00:40:46.440 not in all cases, but certainly with Alzheimer's disease, we're getting a much better sense of

00:40:52.640 which people are susceptible, what genes play a role from a genetic susceptibility standpoint. And

00:40:58.780 genes do play a pretty big role there. And we also understand the other factors. And part of the

00:41:04.780 reason for this, Nick, is there's a very simple but surprisingly accurate adage which states,

00:41:11.740 what's good for the heart is good for the brain. And study after study after study have demonstrated

00:41:18.260 the following. Every intervention that we take to lower the risk of atherosclerotic cardiovascular

00:41:25.580 disease also reduces the risk of dementia. And that means Alzheimer's disease, vascular dementia,

00:41:31.860 which are the two main ones, but also other forms of dementia. So that means having better metabolic

00:41:37.700 health, having lower ApoB, having lower blood pressure, not smoking. Those things dramatically

00:41:46.180 reduce your risk of cardiovascular disease and they dramatically reduce your risk of Alzheimer's

00:41:53.420 disease. Now, an area where dementia has an even bigger positive impact in intervention than

00:42:00.420 cardiovascular disease is with that of exercise. So it's no surprise that exercise improves

00:42:07.300 a person's odds of not getting and or surviving cardiovascular disease, cancer, dementia. But I would say

00:42:15.620 that the evidence for the benefits of exercise are both greater in magnitude and greater in confidence

00:42:23.980 when it comes to the prevention of neurodegenerative disease. So it's interesting because I do think that

00:42:31.100 many people fear dementia more than any other condition and there are very obvious reasons why that would be

00:42:38.200 the case. And it might be that in our practice, we're a bit more optimistic than most based on just the nature of

00:42:47.240 what we do and the types of people that are in our practice, meaning like people who really study

00:42:53.920 prevention and really look at these early, early signs of dementia and look at how specific interventions

00:43:01.800 can make a difference. But unfortunately, the flip side of that is that of all the chronic diseases,

00:43:09.560 the dementing and neurodegenerative diseases are the ones for which we have at this time virtually no

00:43:15.420 viable therapeutic options. So the real name of the game with neurodegenerative diseases,

00:43:22.300 specifically the dementing diseases, and the only other one I'll really mention here briefly is

00:43:26.720 Parkinson's disease because it's the most prevalent movement disorder, is that avoiding them is the

00:43:33.300 first, second, and third priority on a list of three priorities. Once we get into treatment land,

00:43:38.620 at least at this point in time, it's not very promising. So these are both diseases we're having

00:43:44.380 as high a reserve as you can make a big difference. So the higher your cognitive reserve and the higher

00:43:51.040 your movement reserve, the more resilient you are to the effects of these conditions.

00:43:57.800 I think I should just state the conclusion here that we shouldn't ignore the fourth horseman,

00:44:03.220 which is of course the spectrum of metabolic diseases. As I said kind of at the outset, I mean,

00:44:07.940 I think along with cardiovascular disease, we really have a pretty clear sense mechanistically of

00:44:12.880 what's driving this. I mean, this appears to be primarily a consequence of overnutrition.

00:44:18.540 So energy imbalance is really the driving factor of insulin resistance, and insulin resistance is

00:44:28.320 really the driving factor of the downstream effects that ultimately lead to everything from fatty liver

00:44:35.580 disease, type 2 diabetes. And again, these diseases in their own right are quite harmful and

00:44:42.620 devastating. But their real danger of them is the effect that they're having on the other three

00:44:48.600 horsemen, where they're increasing your risk by 25 to 50%. So they really are gasoline on the fire of

00:44:59.120 the other diseases. The last kind of foundational question before we get into tactics would be,

00:45:05.820 we just talked so much about prevention and the importance of it, which if anyone who is younger

00:45:12.040 listening, hopefully encourages them to kind of play that longer game. But what about someone who's

00:45:18.060 older? So they just heard you talk about prevention, the importance of it, and they might be thinking

00:45:23.660 themselves, I wonder if it's too late for me to start thinking about my longevity. What would you say

00:45:30.660 to that? Well, I mean, I think there's like the theoretical answer and the practical answer,

00:45:34.640 right? I mean, I think the theoretical answer is look, while you still have breath in your lungs,

00:45:38.840 it's not too late to do something. But I also think that we're all in a car driving towards the edge

00:45:46.500 of a cliff. It's a lot easier to slow the car down and make sure that you either avoid the cliff

00:45:55.820 altogether or at a minimum, slow your route to the cliff's edge dramatically if you begin the slowing

00:46:02.780 process before you get there. In other words, everybody understands that when you see a red

00:46:08.780 light, you have to be applying the brakes before you reach the actual light. So at some point, I think

00:46:15.820 it is very difficult to back out of a situation. But I also think that that's the rare exception and not

00:46:23.320 the rule. So I've even in the book written about individuals who are in their 70s before they take

00:46:31.440 their first committed step towards health. And these are individuals that in their 80s now

00:46:38.320 are doing better than they were in their 60s from a health perspective, from a movement perspective.

00:46:44.840 So I would absolutely hope that a person listening to us in what might be thought of as their twilight

00:46:51.620 years, who's thinking, man, I wish I did something about this sooner. Is it too late? I would say it's

00:46:57.440 not too late. You'll have to make concessions. You need to start slower. You need to make sure

00:47:02.500 you're not getting injured. I mean, there's an entire playbook and we actually have a podcast

00:47:06.260 around this topic specifically around what would an exercise program for the elderly look like.

00:47:12.380 But I definitely would be very disappointed if anyone thought I was communicating that once you

00:47:18.540 reach a certain age, it's sort of all bets are off.

00:47:20.640 So moving from healthspan, lifespan to now the tactics, I think we'll go through each of them,

00:47:27.740 but I think it'd be helpful at the outset if you just kind of list what the five tactics in your

00:47:34.000 quote unquote longevity toolkit are.

00:47:36.780 Yeah, I just kind of list things into buckets. I wouldn't say this is collectively exhaustive.

00:47:43.460 There are other things that I think matter that don't warrant a bucket in my view,

00:47:48.940 or maybe I should come up with a sixth bucket that I would put every other thing into and we

00:47:53.680 could talk about that as well. But the big five buckets are nutrition, exercise, sleep,

00:48:02.760 pharmacology, and emotional health. Again, we could talk about a sixth bucket, which would be

00:48:09.080 pollution, radical temperature exposure, accident avoidance. So behaviors to avoid harmful accidents,

00:48:17.420 automotive accidents, things like that. So there's definitely also like a grab bag,

00:48:21.760 sixth column that you could include if you wanted to. But I mostly talk about the first five.

00:48:27.760 We'll start with your favorite, which is not ironic in that statement. It is actually your

00:48:32.880 favorite, which is exercise. I think what would be helpful is you've talked about this before,

00:48:37.980 but this framework of the centenarian decathlon, do you want to just quickly state what that is?

00:48:43.320 Because I think it kind of gives some grounding and foundation to how you think about exercise

00:48:49.740 compared to how others may talk about it. So there's so much I could say about this. I really

00:48:55.080 thought you were going to throw me a usual ball and start with nutrition, which of course is not

00:48:59.620 my favorite, but we will talk about it. But you're right. Exercise is my favorite and it is my favorite

00:49:05.760 because I think the data are very clear that exercise, if leveraged to its capacity,

00:49:14.220 has a greater impact on your lifespan. Remember, that's the how long you live peace and your health

00:49:21.680 span. That's the how well you live peace than any of the others, with the only exception potentially

00:49:28.560 being emotional health. There is clearly going to be the case of the individual whose emotional health

00:49:34.920 is in such ruins that until that is addressed, no amount of physical health matters. And in fact,

00:49:42.660 anything else is just prolongation of agony. But if you exclude that case, which is, I don't want to

00:49:48.140 minimize that case because I think there are many people who have been in that situation. Exercise

00:49:53.040 really is the king of interventions. So you alluded to something that is one of my favorite topics,

00:50:00.060 which is called the centenarian decathlon. So I realized that some people have read the book and

00:50:05.480 they understand what this means, or they've heard me talk about it. But again, the purpose of this

00:50:08.960 podcast, I think, is to make sure that someone who's new maybe gets up to speed on this, or it's a

00:50:13.640 refresher for someone. So the centenarian decathlon is an idea that came to me in the summer of 2018.

00:50:19.440 2018. And it's an idea that occurred in an instant, but it was really the result of many years,

00:50:26.620 probably four years of suffering, so to speak. So the suffering started at the end of 2014,

00:50:34.120 when I decided to stop competitively cycling. And not only did I stop cycling, but I was not going to

00:50:42.060 go back to any other sport. So I was not going to be competing anymore in master's swimming,

00:50:47.140 cycling. Obviously, I had no desire to go back and compete in boxing or martial arts or anything

00:50:52.440 like that. Basically, I was done competing, and all I wanted to do was exercise for the sake of

00:50:59.680 exercise. And this, for me at least, was a bizarre foreign idea. Because from the age of 13 until that

00:51:08.280 point in time, which was 41 or 42, I had never trained without a specific purpose.

00:51:17.140 Every single rep, every single lap, every single pedal stroke, everything I ever did

00:51:24.260 was always geared towards a purpose. And now for the first time ever, I was kind of like,

00:51:29.980 huh, what should I do today? I guess I should go for a run. Okay, I guess I'll lift weights tomorrow.

00:51:35.940 I'm in the gym lifting. What am I lifting for? Well, I used to do this. I guess I should still do this.

00:51:41.140 But it was this totally rudderless existence that I had. And it stayed that way until the summer of

00:51:47.000 2018, when I was at the funeral of the parent of one of my best friends. And apologies for repeating

00:51:54.100 this, because I do write about this in the book. But basically, at that funeral, I realized that while

00:52:00.080 my friend's mom had died at a relatively old age, I think about 89, her physical life had basically

00:52:11.160 demised so significantly in the past decade, that her actual death was almost just a matter of

00:52:20.720 formality. But she had lost the ability to do the things that mattered to her most a decade earlier.

00:52:28.260 So she couldn't play golf anymore, because of her shoulder. She couldn't garden because of her

00:52:34.600 knees and hips and back. She couldn't even play with her grandkids. And so she spent most of the 0.76

00:52:40.120 last decade of her life, largely uninvolved in anything, and did come down with dementia in the

00:52:47.320 final year of her life. And that's what ultimately took her life. But I was just totally blown away by this

00:52:54.200 person that I once remembered as being completely vibrant, losing everything and spending this last

00:53:00.160 year in this state. And I realized in that moment, as I literally sat in a church pew, first of all,

00:53:06.700 this is really common. And secondly, this is what I want to train for. For the first time in four years,

00:53:14.860 realized, aha, the thing I want to train for is to avoid this. I want to come up with an event,

00:53:24.240 an athletic event, that will be done at the end of my life, and everything between now and then will

00:53:31.580 be training for it. And so I just came up with this idea called the centenarian decathlon. Not because

00:53:39.800 it implies that one has to live to a hundred to compete, or not even to imply that it has to have

00:53:45.980 10 events, but simply as a mental model to say, what are the most important activities, both activities

00:53:54.800 of daily living and activities of performance that I want to be able to do at the end of my life?

00:54:01.040 And how well can I define them? How well can I understand the physical traits that will be

00:54:09.000 necessary to execute them? And then how much can I reverse from there or back cast from there,

00:54:15.580 what I need to be doing today to increase the probability of doing those things tomorrow to

00:54:21.440 the highest level. And that has become obviously a huge obsession of mine. As you know, I, along with

00:54:29.260 a couple of other folks have started a company around this called 10 squared, which is just geared

00:54:35.500 towards training people to do this. And I think that it is at least until someone shows me a better

00:54:42.740 idea, the best model for how to train if your goal is not something very specific. So again,

00:54:49.880 if you came to me and said, I know how much you love jujitsu. If you're like, look, there's this

00:54:54.380 tournament coming up in six months and I really want to compete for it. That's not the centenarian

00:54:58.620 decathlon. That's a very specific type of training you need to be doing in jujitsu to go and compete

00:55:03.660 there. If you know, my wife is running the Boston marathon next year and she wants to run a certain

00:55:09.200 time, she will have nothing to do with training her centenarian decathlon. She is going to be doing 1.00

00:55:15.380 very, very specific running workouts to make sure she hits her goals. So there are lots of other ways

00:55:22.000 to train. But my point is that most people aren't training to be the best at their local jujitsu

00:55:30.180 tournament or to run their PR at the Boston marathon. And even if they do those things,

00:55:36.340 they're usually fleeting. And ultimately what people really want to be training for

00:55:41.240 is to be the most kick-ass versions of themselves in the last decade of their life. And again,

00:55:48.720 if that means your 80 to 90 years are functioning like you're a really good 70 year old, that's a

00:55:55.880 totally different experience from what most people go through. Let's say someone is training for the

00:56:02.460 centenary decathlon. So they kind of agree and they say, I want to put all my focus into this,

00:56:08.080 which is how do I become an athlete focused on life? And we don't have to get into these in detail

00:56:14.400 because in the show notes, we'll link to the multiple, multiple places we've talked about them.

00:56:19.320 But what are the four components that you think are important for someone who is interested in

00:56:25.860 training for the centenary decathlon? It starts on the foundation. You have to have stability. You

00:56:32.180 have to have the chassis. Basically, I'd say the chassis and the tires. You have to have every aspect of

00:56:39.100 the motor control, coordination, ability to dissipate force, ability to receive force,

00:56:47.260 ability to balance. There's so much that goes into stability that it, I think, got a full half

00:56:53.020 chapter in the book. And it's far and away the most complicated to explain, but it's really obvious

00:56:58.420 to see it when it's not there. So every one of us is lacking in stability. And it was the biggest

00:57:04.380 re-education for me as I pivoted to this way of training. So it's everything from learning how to

00:57:11.500 appropriately pressurize your intra-abdominal space to how to unlock your ribs, maintain an appropriate

00:57:18.940 center of gravity, how to be able to isometrically contract muscles as necessary, how to be able to

00:57:26.140 do it under control, how to have good foot mechanics, right? I mean, all of these things we've

00:57:30.340 done dedicated podcasts on because each component of this stability game is quite nuanced. And the good

00:57:37.020 news is while most of us show up to the middle part of our life with enormous deficits here,

00:57:42.040 they're all retrainable. We're actually still quite plastic in our old age. Second component is

00:57:47.000 strength. And I would say a sub-component of strength is power. So even though we lose power

00:57:52.260 very quickly as we age, the more we can maintain it, the better. And you can't have power without

00:57:58.080 strength and stability. The third component, and this is really more of a continuum, the third and

00:58:03.540 fourth are part of a continuum of cardiorespiratory fitness. I talk about this as being a triangle.

00:58:08.860 So the base of the triangle is the aerobic efficiency. So this is the maximum fat oxidation.

00:58:16.120 This is your all-day pace. We want that to be as high as possible. And then the peak of the triangle

00:58:20.680 is the VO2 max. That's most adequately thought of as the engine size. So that's the peak aerobic output.

00:58:26.620 Those are the four components. And one of the exercises we do with both our patients,

00:58:32.320 and obviously the clients in 10 squared is, once you have a person's centenarian decathlon goals,

00:58:38.640 you break them down into what is required. So if you give me your list, we can take that list and

00:58:46.200 we can say, oh, this requires a VO2 max of 31 milliliters per kilogram per minute. This requires

00:58:52.860 an ability to sit this way, or this requires this much strength in this domain. This requires this type

00:58:58.780 of hip loading, et cetera, et cetera. And then we can evaluate where a person is today and then say,

00:59:04.520 oh, okay, well, obviously today you can do all of those things, but here's the predicted trajectory

00:59:10.000 of decline on each of those things. And will you be above your benchmarks in 40 years, or will you be

00:59:16.700 below them? And for most of us, myself included, at least on some of those dimensions, you're actually

00:59:22.080 considerably below them at your target. And therefore you have to raise the performance

00:59:27.780 currently to make sure you hit the targets in the future.

00:59:32.720 And like we mentioned, for anyone who is interested in further on anything, exercise in the show notes,

00:59:37.720 we'll link to the multiple podcasts, articles, et cetera. So people can dive in, but moving from

00:59:43.900 exercise to your second favorite nutrition, what's your framework for how you think about nutrition?

00:59:49.620 Because you don't necessarily think about nutrition as some people talk about it, which is this diet's

00:59:54.880 best or this diet's best. You kind of look at it a little bit of a different way. And so do you want

00:59:59.680 to walk people through your framework and how you assess nutrition and where someone is at in their

01:00:06.960 nutritional state?

01:00:08.760 Yeah. I mean, I would say that nutrition is a very complicated thing to study. I would say it's the

01:00:14.460 messiest of all the pillars to study, probably even messier than emotional health, although maybe

01:00:21.740 that's debatable, but the reasons for it are obvious and not worth restating. But it's for that

01:00:27.740 reason that there were very few things that can be stated in this field with a high, high degree of

01:00:33.680 certainty. So unfortunately, the challenge in nutrition is you have a lot of people that speak

01:00:39.440 with such insane conviction and they talk about something as though it is absolutely correct,

01:00:49.160 even though if you were putting an error bar on their statement, it would dwarf anything they're

01:00:55.540 saying. And truthfully, I have been guilty of this. I think 12 years ago, I was talking about nutrition

01:01:02.560 with a level of certainty that I don't think was warranted. And so as the adage goes, the further

01:01:10.180 you get from the shore, the deeper the water. And I think in my older age, I'm actually quite far out

01:01:17.040 from the shore. And I realized the water is awfully deep out here. And there aren't a lot of things that

01:01:23.340 can be stated at a high enough degree of certainty that you should act on them with almost blind faith.

01:01:30.660 So here are the two that I can tell you with a very, very high degree of certainty. The first is that

01:01:39.620 the single most important input from nutrition to a person's overall health is energy balance.

01:01:49.580 Stated another way, the energy input of food is the first order determinant of health. Maybe stated

01:01:58.920 another way, the total calories you consume would be the most important thing. Not the only thing.

01:02:09.400 I do not want to suggest that a thousand calories of Tic Tacs is the same as a thousand calories of

01:02:16.140 broccoli. It is not. But I'm also talking about this through the lens of common sense. And the truth

01:02:23.620 of it is, if you subside on a diet of Tic Tacs, you're going to eat a lot more than a thousand

01:02:28.440 calories of them because they're not satiating and they're junk and they're hollow. So I want to be

01:02:33.300 very clear that the primary input is total energy, but it is also impacted by many other things,

01:02:43.540 including diet quality, processing, and macronutrient distribution.

01:02:49.220 The second thing that is abundantly clear is that protein is the macronutrient we should be least

01:02:58.900 flexible on. Stated another way, we can be quite flexible on how much carbohydrate and fat we consume

01:03:07.160 to fill our energy needs. But because protein is not consumed for the purpose of ATP generation,

01:03:16.540 which is the principal reason we consume carbohydrates and fats, although fats are also

01:03:21.780 essential for some structural purposes, we cannot be too flexible or compromising in our protein

01:03:28.960 requirements. In other words, if you really wanted to just come up with a single number to give people,

01:03:34.980 I would say on average about 1.6 grams of protein per kilogram of body weight should be consumed by

01:03:43.540 everybody. Now, again, I hate saying that because there's truly nothing that you can say across the

01:03:49.180 board. There are clearly people who, based on what they're eating, will need more protein and there

01:03:54.960 are probably people who can get away with a little bit less. If you took a perfectly high quality

01:04:00.120 PD-CAS 1.0 protein in a person who's not over the moon active, they could probably get away with 1.2

01:04:08.500 grams or even 1 gram. But boy, anything below that and you're starting to really miss out. And by the

01:04:14.280 way, as you age, those requirements go up due to anabolic resistance. So again, we can talk all day

01:04:22.260 about every diet under the sun and every religion and every faction of every religion around every

01:04:30.100 dietary tribe. But the truth of it is, it's really hard to find a scientist, an actual nutrition

01:04:37.780 scientist. I'm not talking about an influencer. I'm not talking about a health blog. I'm talking about

01:04:44.400 actual people who work in labs doing nutrition who will disagree with that statement. There are some,

01:04:51.140 but they are in the huge minority. And interestingly, they tend to avoid using human data when they talk

01:04:59.480 about those things. But when you limit yourself to the species of interest, which is humans,

01:05:04.440 not rodents, and you talk about experimental data coupled with other insights, those two things seem

01:05:11.420 to matter the most. How many calories are you getting? Not too much, not too little. Are you

01:05:16.540 getting enough protein? Obviously, there are other terms. We certainly want to make sure you're getting

01:05:21.220 enough micronutrients as well and that you're avoiding toxins. That tends to be less of an issue today

01:05:27.340 than it was a hundred years ago. But of course, that's also really interesting. But a lot of the

01:05:32.420 other stuff, Nick, is details. So when I'm looking at a patient, given how important those things are,

01:05:39.140 to me, it makes sense to be evaluating those things at the outset. So when we do a DEXA scan on somebody

01:05:46.040 on day one, and we can see how much subcutaneous fat they have, how much visceral fat they have,

01:05:51.260 how much muscle mass they have, and we can do a lot of advanced blood work and see how metabolically

01:05:57.220 healthy they are, how well they dispose of glucose, all these other things, I can very quickly answer

01:06:02.200 three questions. Literally, on first contact, are you overnourished or undernourished? And that really

01:06:09.060 comes down to energy balance. How much fat do you have on your body and how well is it distributed

01:06:16.140 throughout your body? Where is it distributed? Second question, are you adequately muscled or are

01:06:22.800 you under-muscled? Third question, are you metabolically healthy or not? And when you can

01:06:29.300 answer those three questions, which you can in a very short period of time with a relatively small

01:06:35.100 amount of data, that tells you, does this person need to eat more, less, or the same total energy,

01:06:41.260 the same amount of protein or less, and how important and what type of exercise should they

01:06:48.300 be doing to augment our findings? Because we're talking about nutrition, I'll close this out by

01:06:53.360 saying most people, when they do this, come out slightly in the overnourished category. That's just

01:07:00.120 another way of saying most people are overweight or obese. I think the numbers are probably 70% of the

01:07:07.380 population are overnourished or significantly overnourished. Therefore, most people, when you

01:07:15.080 go through that whole treatment algorithm, are going to be in the I need to eat less camp. If you are in

01:07:21.980 the I need to eat less camp, you now have three ways to do that, three strategies, if you will. The first

01:07:30.100 is directly reducing caloric intake. So that says, agnostic to what or when I eat, I will simply eat

01:07:39.980 less. This is the most direct way to do it. It has lots of pluses and minuses, which I've discussed in

01:07:46.280 so much detail in other podcasts that we'll link to. The second method is, I will identify something or

01:07:53.940 some set of things in the diet that I will remove from the diet. I will restrict them. This is called

01:08:00.300 dietary restriction. And the more restrictive the elements of your diet, the more effective this

01:08:07.880 technique is. So if you only choose to restrict lettuce, this will have no effect. If you restrict

01:08:15.540 everything but potatoes, meaning if the only thing you allow yourself to eat is potatoes, this will have

01:08:21.160 an enormous effect. So the more you restrict, the better that works. And then the third strategy is

01:08:26.680 time restriction, where you limit the window in which you eat. And the narrower and narrower that

01:08:32.280 window, the greater the likelihood that you will overall induce a caloric deficit. So there's a lot

01:08:39.480 more I can say about nutrition. We could get into the nuances of which type of fats are better.

01:08:45.320 Saturated fats, monounsaturated, polyunsaturated fats. Is a Mediterranean diet more efficacious than a

01:08:50.600 low-carb diet or a low-fat diet? And all of those things, again, I've written about, I've spoken

01:08:55.940 about. But I think from the standpoint of what are the most important things, I think you've got it.

01:09:00.900 Have you remembered what you ate for lunch yet? That's, I think, the only thing from the nutrition

01:09:05.400 conversation that's missing. I scarfed down some leftover spaghetti squash that we made yesterday.

01:09:11.280 And what else did I have? Oh, I had a container of blackberries and I had some venison.

01:09:19.800 There you go. Great. Moving on to sleep. So sleep is something you've written about where

01:09:25.540 you take it much more seriously now than maybe you used to in the past. So do you want to talk

01:09:31.540 about why you think sleep is such an important component of not only lifespan, but also healthspan?

01:09:38.820 Well, I think the data really make the case more compellingly than I need to. Fortunately,

01:09:45.500 short-term sleep deprivation is easy to study and it unequivocally demonstrates a remarkable

01:09:51.580 negative impact on cognition, on physical performance, on physical markers of health,

01:09:59.540 such as insulin resistance, on appetite. Everything that can go wrong in the human body

01:10:05.460 goes wrong when you are sleep deprived. And again, what's nice about this is you don't need to do

01:10:12.080 five-year studies to figure this out. You can do two-week, three-week studies where you take people

01:10:18.820 down to four hours a night of sleep and you can absolutely destroy them in every physiologic measure

01:10:27.600 during the wakeful period of their lives.

01:10:29.800 So we can then extrapolate from there that, okay, well, if you're only sleeping five and a half or

01:10:36.660 six hours a night, you're probably not getting as much of the negative effects. But when we see and

01:10:44.980 measure other effects that are negative to a lesser extent, it seems pretty easy to attribute them

01:10:51.380 to the reduction of sleep. So in other words, when you look at a person who's not sleeping as

01:10:57.040 inadequately as people are typically studied in short-term studies geared towards identifying

01:11:03.580 the risks, they get many of the same problems, but just not as extreme, suggesting there's a dose

01:11:09.880 effect to sleep reduction. And truthfully, I think that this is something that I think society is far

01:11:16.960 more willing to entertain today than 10 years ago. I think Matt Walker, who's also a very close

01:11:22.420 personal friend, has had a lot to do with this. Arianna Huffington has brought a lot of attention 0.99

01:11:27.640 to this. So I think there are many people out there that are saying, hey, this whole idea of

01:11:32.660 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

01:11:38.300 adopt that mantra. So you will indeed sleep when you're dead and you'll be dead sooner than you want 0.90

01:11:42.720 to be. So again, I think that this one doesn't require a lot of convincing, but how to do it, of course,

01:11:48.020 is a little more complicated. The good news is there's really a lot of wonderful behavioral tools

01:11:53.400 and ultimately for some people, pharmacology or mechanical assistance such as CPAP, if a person has

01:12:00.000 apnea, there are technologies, both pharmacologic and otherwise, that can really help here. But for most

01:12:06.060 people, the behavioral tools do the work. This is really one of those things where very few people

01:12:14.200 need to see a physician to help them sleep or to troubleshoot a sleep problem. And when you do,

01:12:20.480 fortunately, there's an entire branch of medicine dedicated to sleep physiology. There are actual

01:12:26.560 physicians who specialize in this and we're certainly not afraid to use them when it's necessary.

01:12:32.320 There's also a field of behavioral therapy called cognitive behavioral therapy for insomnia

01:12:37.020 that is an entire discipline that is dedicated towards the cognitive tools that you can use

01:12:43.960 during periods of insomnia. So we always get patients in our practice who just have what can

01:12:50.740 only be described as the most abjectly horrible sleep. And of all the problems we face, this is the

01:12:56.980 one that I tend to be most optimistic about our ability to help in a relatively short period of time.

01:13:02.440 We have a whole AMA dedicated to sleep along with multiple Matt Walker episodes. So I don't think

01:13:08.460 we needed to get into insane detail because we will link it in the show notes, but you mentioned

01:13:13.360 a few of the behavioral tools. And so if someone says, okay, I need to take more awareness in my

01:13:19.200 sleep, I need to do more to get better sleep. What are some of the things that they can look at and

01:13:23.680 evaluate? I would say if we were in an elevator and we had only between the first floor and the 15th

01:13:29.680 floor for me to tell you everything that mattered, I would say, try to go to bed at the same time and

01:13:34.520 wake up at the same time every day. Give yourself about eight hours to be in bed, make the room as

01:13:40.660 dark as possible, as cold as possible, and detach yourself from anything stimulating, especially

01:13:48.720 upsetting, which is work, social media, that kind of stuff for two hours before bed. And if we haven't

01:13:55.060 hit the 15th floor yet, I would say, try to not eat or drink any alcohol for three hours before bed.

01:14:02.540 Those would be the no risk, no regret moves to try to fix your sleep. And that's a lot, by the way,

01:14:09.280 I'm not suggesting that would be easy to do for someone who's doing none of them. But if you gave

01:14:14.400 me a hundred people who were complaining of poor sleep and, or objectively had measurements of poor

01:14:20.460 sleep and all a hundred of them did that, I think 80 of them would get better. Moving to drugs and

01:14:26.560 supplements. This is something that if you look at all the different drugs, pharmacologic, if you look

01:14:31.780 at all the supplements, we have an insane amount of content on, impossible to answer all the questions

01:14:36.980 here that come in. But I think helping people understand just what their relationship with drugs

01:14:42.120 and supplements should be, how they should think about it, how they should not think about it. How do you

01:14:46.800 talk to patients about that who come in to the practice and maybe have a list of 20 supplements

01:14:51.760 that they show up with? Yeah, that's definitely one phenotype. I would say just to kind of address

01:14:56.940 both extremes, you have some people who think everything is solved by drugs and supplements.

01:15:03.180 And then you have people who think you should never take a drug or a supplement. And so I just always

01:15:09.640 kind of try to remind people drugs and supplements are just a tool to say, I never want to take a drug

01:15:15.040 is kind of like telling a contractor, Hey, please do a good job building my house, but just never use

01:15:20.800 the hammer or never use the Phillips screwdriver. You can use the Robertson, but not the Phillips.

01:15:26.000 You just want to have tools. We just want to have tools and the best contractor and carpenter

01:15:31.940 and tradesman is going to have the most tools and the most facility with knowing how and when to use

01:15:38.260 them. So that said, we do kind of, especially on the supplement side, have a framework because as you

01:15:44.880 said, there's a infinite number of supplements. There's a finite number of regulated drugs,

01:15:49.100 but a non-finite number of supplements. So you have to have a framework for this thing.

01:15:54.200 And so the first question I'm always asking myself with any exogenous molecule is,

01:15:58.780 is this a molecule that is being taken to lengthen lifespan or improve healthspan? You would be

01:16:08.040 amazed at how many times I ask somebody who's taking a supplement, which of those two they're

01:16:13.700 taking it for. Usually you get a very blank stare. I'm taking it because fill in the blank influencer told

01:16:20.460 me to take it. Okay. So let's say we can establish that you are taking this for one of those reasons.

01:16:26.620 It's either going to make me live longer and, or it's going to improve my physical,

01:16:30.780 cognitive or emotional health. The next question I would say is, okay, if this is a lifespan enhancer,

01:16:35.680 if this is going to make you live longer, is it doing it by targeting a specific disease

01:16:42.500 or is it a broad gyro protective molecule? Similarly, if you're telling me this is a healthspan

01:16:48.800 enhancer, is it specifically enhancing cognitive health, physical performance, emotional health,

01:16:55.480 or is it sort of acting through some mechanism we don't understand? I would ask if we have safety

01:17:01.500 data on this. I would ask if we have efficacy data in humans and, or in animals, if not, and if in

01:17:09.220 animals, how relatable is it? If it's a supplement, I would ask, how can we control for purity? How do we

01:17:16.520 know that what the bottle says is in it is actually what's in it and that nothing that's not supposed to

01:17:21.560 be in it isn't in it? There are a few more questions, but that's the long and short of it.

01:17:25.600 And so I think one needs to go through that type of exercise and put that type of filter to

01:17:31.960 everything. And then, and only then I think, should we go down the path of, okay, what supplements do

01:17:37.260 we want to use? Where do we want to turn to pharmacology, hormones, those things.

01:17:41.860 Moving to the last tactic, and you talked a little bit about this because emotional health fits in

01:17:46.520 the health span bucket as well. But when people think about longevity, emotional health is not

01:17:52.900 something that usually comes up a lot. And so what would you say to someone who maybe is taking the

01:17:59.260 steps in their nutrition, their exercise, their sleep, drugs and supplements, but not necessarily

01:18:04.880 focusing on their emotional health? What would your advice to them be on how emotional health,

01:18:11.420 you don't necessarily correlate it all the time with longevity, but you find it to be an important

01:18:17.860 aspect? Well, I mean, I think there's two components. I think there is enough evidence,

01:18:23.120 though you could never prove it, that a person who's managing their stress better, who's happier and

01:18:29.480 who has better relationships probably also lives longer. Certainly the epidemiology suggests all of that.

01:18:35.680 That's not unclear, but I'm acknowledging that that would be very difficult to demonstrate causality.

01:18:40.220 People could be happier and have better relationships and all those things because their health is

01:18:43.740 better. So it could be reverse causality there. But I think there's actually enough evidence that

01:18:48.820 there's at least bi-directional causality there. But I think to help somebody think about this,

01:18:53.900 I would say just forget that. Let's pretend that being miserable, lonely, and angry helped you live

01:19:02.420 longer. And that if you were happy and you had great relationships and you were in harmony,

01:19:08.380 you would live shorter. Who would choose the former when you frame it that way? Outside of extremes,

01:19:16.180 like, okay, happy people can't live past 30, miserable people can live to 100. I'm sure a lot

01:19:21.400 of people would say, well, I'd rather be miserable at 100. But the truth of it is, even framed that way,

01:19:25.840 it seems ridiculous. So all of that is to say, as a thought experiment, just forget the lifespan piece

01:19:31.980 of this. Just think of it through the lens of common sense. Why would you ever choose to be

01:19:39.520 unhappy? It doesn't make sense. And I think what maybe for me was a big insight late in life was

01:19:47.680 you can do something about this. Everybody's got a story. Everybody's got a history. Everybody's got

01:19:53.580 a background that brings them to the table, but it's all modifiable. So the software can be modified

01:19:59.240 is the point. And we've got so much content on this that I obviously couldn't go into it in any detail

01:20:05.260 here. But I think the most important thing for the purpose of this discussion is that this entire area

01:20:11.200 is as important, potentially more important than all of the others, because without this one in check,

01:20:18.180 the other ones don't matter. Peter, I think that kind of wraps what we were hoping to cover. And

01:20:23.380 again, as we kind of mentioned on the outset, the idea is not to get into the super intense details on

01:20:30.180 everything. We'll link to that, but more so cover high level longevity 101, how you think about some

01:20:37.220 core aspects for people who are newer, people who need a refresher. I think the last thing that we

01:20:44.720 should end with is just if someone is new and they're listening to this and they maybe feel

01:20:49.200 a little bit overwhelmed on where they should start, right? A lot of information came out of

01:20:53.480 them on the lifespan, health span, different diseases, different tactics. What advice would

01:20:57.780 you give someone who is listening and they would say, I want to take this more seriously, but I'm a

01:21:02.740 little overwhelmed on where to start? I would say just pick one. It's not a race. And I think

01:21:09.880 finding something that you think you're going to be successful in would be the best first place to

01:21:15.980 start. So if after listening to everything we just talked about, you're kind of like, you know what

01:21:20.420 really resonates with me? My sleep probably sucks. Then I would say, how about you change nothing in 0.97

01:21:26.460 your nutrition, nothing in your exercise. Don't do anything else. Don't buy a supplement. Just work

01:21:33.720 on implementing the stuff we talked about on sleep. Because if you get that better, it's going to do

01:21:39.340 two things. It's going to make it easier for you to address the other things. And it's going to give

01:21:44.460 you the confidence and agency that says, Hey, I actually have control over this thing. It's not

01:21:49.640 out of my hands. Awesome. Well, Peter, hopefully people enjoyed this special episode, but thank you

01:21:55.240 for your time and we'll see you on the next one. Sounds great. Thank you for listening to this week's

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The Peter Attia Drive - July 29, 2024

#311 ‒ Longevity 101： a foundational guide to Peter's frameworks for longevity, and understanding CVD, cancer, neurodegenerative disease, nutrition, exercise, sleep, and more

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