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Peter Attia | Outlive: The Science & Art of Longevity | Talks at Google

Founder of Early Medical, Peter Attia, MD, joins us to discuss his book "Outlive: The Science and Art of Longevity," a groundbreaking manifesto on living better and longer than conventional medical thinking on aging and reveals a new…

Tara SeppahostPeter Attiaguest
Dec 5, 20241h 0mWatch on YouTube

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Transcript

  1. 0:00 – 0:07

    Intro

    1. TS

      [on-hold music]

  2. 0:07 – 4:45

    Peter Attia’s unconventional path: boxing, engineering, medicine, McKinsey, and personal health

    1. TS

      Hi, everybody. Thanks for joining us today. Thank you so much, Peter, for being here. I'm gonna read your bio, and then we'll kinda dive in. [laughs] Cringe. Um-

    2. PA

      [laughs]

    3. TS

      All right. Peter Attia, MD, is the founder of Early Medical, a medical practice that applies the principles of Medicine 3.0 to patients with the goal of simultaneously lengthening their lifespan and increasing their healthspan. Dr. Attia received his medal degree- medical degree from the Stanford University School of Medicine, and trained for five years at the Johns Hopkins Hospital in general surgery. He's the host of The Drive, one of the most popular podcasts covering the topics of health and medicine, and he's also the author of the number one New York Times bestseller, Outlive: The Science and Art of Longevity, which will be the topic of our discussion today. Peter, thanks for joining us.

    4. PA

      Thank you for having me.

    5. TS

      Yeah. Um, so personally speaking, uh, as I shared with you before we got here, your book changed my life, and I'm really, you know, grateful for the opportunity, uh, for you to, to be here today and share your work with a broader audience. So before we dive into the book, I wanna learn a little bit more about you. Uh, many of us know you as physician, author, podcaster, et cetera-

    6. PA

      [coughs]

    7. TS

      ... specializing in longevity. But can you tell us a little bit about just your path to get here?

    8. PA

      Um, yeah, it's not... I mean, it, uh, what's the... There's an expression about how things always make sense in retrospect, but maybe not at the time. They don't seem that logical. There, there's a more eloquent way to describe that. Um, I, uh, you know, growing up didn't, didn't particularly care for school. Um, was really enamored with boxing, and that's... I wanted to be a professional fighter. Um, and that was, that was essentially my life until my final year of high school, when an amazing guy, who was my- one of my teachers, um, I think, you know, probably one of the first pivotal, uh, moments in my life was when this, this teacher called me in early one morning. And, um, interestingly, rather than sort of browbeating me for not applying to college-

    9. TS

      Mm-hmm

    10. PA

      ... you know, he just said, "Look, I think you, you know, you really have a talent for math. I think you'd be crazy..." He didn't even say it that way. He goes, "I think you would be depriving the world of something if you didn't pursue your talents in mathematics." And I just, even though I didn't like school, I loved this teacher. Um, and something about that just really got me thinking. And, uh, ultimately, I ended up needing another year [laughs] to apply to college.

    11. TS

      [laughs]

    12. PA

      Uh, but, but I ended up going and following in his footsteps, doing engineering and math together. Um, and, uh, and then I had another change of heart, which is a long story that I won't get into. And after I completed all of that and was just about ready to start my PhD in aerospace engineering, realized I actually wanted to do medicine instead, and then I needed to [laughs] spend another year screwing around to take-

    13. TS

      [laughs]

    14. PA

      ... pre-med courses, which I'd never taken. I'd never taken a biology course. A funny story, when I took the MCAT, I hadn't actually taken biology yet, and it was only the night before the MCAT that I realized meiosis-

    15. TS

      Gosh

    16. PA

      ... and mitosis were different, and it wasn't a typo.

    17. TS

      [laughs]

    18. PA

      The entire time I was going through the practice test, I was like, "How, how sloppy of these books that they can't-

    19. TS

      [laughs]

    20. PA

      ... even spell-check them, for heaven's sakes."

    21. TS

      [laughs]

    22. PA

      And then, then luckily the night before I figured that out. Um, so, uh, so then I, you know, I, I went to med school and, uh, uh, you know, thought I was... Like everybody, you sort of go into medical school thinking you're gonna do one thing. I thought I would do pediatric oncology, but then decided I really wanted to do surgery. Um, and then it interestingly, when I was still two years shy of completing my seven-year residency, I just had another change of heart and realized-

    23. TS

      [laughs]

    24. PA

      ... I'm not happy doing this. I'm gonna leave. Um, decided I would go and get an MBA, um, and then met somebody who told me about this company called McKinsey, where you basically get an MBA but get paid. And I was like, "Well, that sounds like a better idea 'cause I have so much debt at this point in time."

    25. TS

      [laughs]

    26. PA

      Um, so then I went off to McKinsey for a couple years. Didn't do healthcare, did, uh, credit risk, which was, um, the, the most amazing time to be there. 2006, 2007, 2008-

    27. TS

      Mm

    28. PA

      ... in the lead up to the mortgage meltdown, was, um, like being a kid in a candy store if you enjoy quantitative stuff, which I do and did. Um, and then to make a long story short, I just sort of became interested in my own health, and that was actually the journey that kinda led me to doing what I do now, and have done for the past 10 years, which is sort of really think about this idea that at the time I wasn't calling Medicine 3.0, but that I now call Medicine 3.0.

  3. 4:45 – 7:19

    Defining “longevity” through lifespan vs. healthspan (physical, cognitive, emotional)

    1. TS

      Yeah. Great. Thank you. That's actually a good, uh, sorta onboarding into some of the concepts of the book. So, um, you describe Outlive as an actionable operating manual for the practice of longevity, and that's a term that gets used re- you know, loosely and thrown around a lot. Can you sort of describe how you think about longevity, and maybe share a little bit about the terms that you use, lifespan versus healthspan?

    2. PA

      Yeah. Um, [clears throat] I do make a point in the book of saying how much I don't like the word longevity, but it's not because the word doesn't have meaning. It's because it's been, I think, uh, hijacked-

    3. TS

      Mm-hmm

    4. PA

      ... to mean a lot of things that I don't necessarily think are, are relevant and, and in many cases I think are actually just kind of harmful or silly. Um, but for whatever it's worth, the, the word is here, and it's clearly a heuristic for something. Um, but I do think it is important to differentiate between lifespan and healthspan, as they are two different components. So for example, when we talk about [clears throat] the increase in lifespan, um, of, for example, people in the United States over the past 100 years, it's profound. There's been a doubling of lifespan. Um, and that's obviously a part of longevity, but it's not the only part. Um, and, and so there must be this other part that's not as obvious.

    5. TS

      [coughs]

    6. PA

      And, and I think healthspan is less obvious because it's harder to define, harder to measure, and frankly, it's not binary, right? You guys are engineers, so we love digital things, right? It's zero or it's one, and that's it, and that's what lifespan is. But healthspan is not. So [clears throat] I think in part, you know, the expression what's get, what gets measured gets managed [clears throat] is very true here. And I think that historically the medical system measures lifespan [clears throat] and we've managed it pretty well. [lips smack] But, um, but healthspan is more complicated because it has components that are somewhat subjective, and even the things that are objective are a little squishier, right? So cognitive health, you can measure certain elements of that. You can measure processing speed, you can measure memory, short-term memory, long-term memory, visuospatial memory. Um, but we don't typically do these things, and therefore I think it's harder for people to kinda wrap their mind around what is healthspan. Um, so for me it has three pieces. It has a physical piece, it has, um, a cognitive piece, and it has an emotional piece. And those are broad terms, so you might say, "Well, how can it only include those three things?" But if you unpack what each of them is, you'll, you'll see that there's quite a lot there. So I would say in summary, lifespan, uh, pardon me, longevity is about the pursuit of in- increasing both of these.

    7. TS

      Yeah. Great.

    8. PA

      [clears throat]

  4. 7:19 – 10:38

    From “fast death” to “slow death”: the Four Horsemen of chronic disease

    1. TS

      Um, so, so building on the concept of healthspan, in the book you talk about, you know, the Four Horsemen and, uh, describing the toll that chronic disease has taken on our, our lives. Can you talk a little bit about the Four Horsemen, uh, and just share your perspective on, you know, maybe methods that we can s- sort of stave them off?

    2. PA

      Yeah. So for-

    3. TS

      [clears throat]

    4. PA

      You know, h- humans have been around for about 250,000 years, so there's, uh... It's, like, kind of interesting. I was, uh, meeting with a friend yesterday and he was commenting on how remarkable it is that in 1950 there were only a billion people on the planet. Today, uh, on the planet in 1950, and today of course we're at eight, and, you know, relatively shorter we'll be at 10. And I said, "That's interesting, but what's more interesting to me is that there have been 110 billion people on this earth in the past 250,000 years." Like, you don't realize the value of all that time. Also very interesting and totally an aside, there was a paper that came out in Science last year [clears throat] that talked about a few choke points in human civilization. I don't know if any of you saw this, but there were at least two or three points when they, they believe the human population was down to as little as 4 to 8,000 people, meaning we came really close to extinction many, many times over the last, uh, 250,000 years. [lips smack] So, um, [clears throat] this idea that up until very recently across that huge timeframe of, you know, 250,000 years, virtually all death was pretty quick. You died of infections, you died from trauma, and, uh, w- women and their babies died during childbirth. That basically accounted for why, uh, life expectancy didn't really exceed 40. [lips smack] Now, in a very short period of time, 'cause if you're drawing this on a graph and you're looking at it in linear time, it looks like this, life expectancy, right? It's a total step function over 100 years. Um, but we traded what I call fast death for slow death.

    5. TS

      Mm.

    6. PA

      So the advent of Medicine 2.0 made those causes of death much less common. Infections, communicable diseases, uh, infant mortality, and trauma have fallen dramatically because the tools of Medicine 2.0 are really good at treating those things. And so now that the tide has gone out and you can see who's not wearing their shorts, you realize that what's really going on now that we've survived those fast causes of death is we die from slow things. Um, [clears throat] and I term them the Four Horsemen, but, uh, you know, it's basically the things that everyone knows, right? So it's cardiovascular and cerebrovascular disease at number one, cancer at number two, [lips smack] uh, neurodegenerative diseases and dementing diseases, uh, at number three. And I say that 'cause remember there's a lot in there, right? It's not just Alzheimer's disease, it's Parkinson's disease, Lewy body dementia, vascular dementia, et cetera. [lips smack] And then the fourth horseman, you know, doesn't kill nearly as many people as the others, but I would argue it is the foundation upon which all of those diseases are amplified, and that's, that's the continuum of metabolic diseases that, that spans the gamut from insulin resistance to fatty liver disease, uh, to Type 2 diabetes. Um, and that is at, from a growth rate perspective, increasing more rapidly than the other three, and it is by extension accelerating the other three.

  5. 10:38 – 13:00

    The marginal decade: why the last decade shapes the quality of a life

    1. TS

      Yeah. I have a question about that a little bit later, so we'll, we'll dive in there. Um, but just to sort of finish out on defining some of the concepts that you introduce in the book, you talk about this notion of the centenarian decathlon and the marginal decade. Uh, can you, you know, share a little bit about what those things are and why they matter to us as we age?

    2. PA

      [lips smack] So [laughs] I'm gonna try to do this. I've never been successfully able to do this. Every time I try to explain or I'm about to explain, everyone goes, "What are you talking about?" So I'm not gonna be offended if you guys are like, "This doesn't make any sense." Um, in oil markets, the oil price is set by the marginal barrel price, right? So if the worldwide demand for oil is 87 million barrels of oil a day, I don't even know what it is anymore by the way, but that's probably directionally where it is, the price is not set by the low-cost barrel, the ones that are reazy, really easy to pull out of the Ghawar oil field. The price is set by the marginal barrel. The last one that comes out of the ground is the one that's setting the price. And it sort of occurred to me that when I was looking at the longevity curve, that there was a parallel here, which is the quality of our life is not determined by the first decade or second decade of our life. In many ways it might be determined by this marginal decade. In other words, w- when I see people whose final decade is filled with suffering in some capacity, it could be physical suffering, it could be cognitive suffering, it could be emotional suffering. So you could take somebody who's in perfectly great health, but they've lived such a miserable life that they spend the last decade of their life alone 'cause they don't have anybody that they love and nobody wants to be around them. To me, that's- That's a bad marginal decade. Um, you take an individual who's never looked after themselves physically, maybe they have their cognition all about them, but, you know, they can't do anything. They can't... They're in so much pain, or they can't be mobile. To me, that's a suboptimal marginal decade. And so it occurred to me that if we could target making the marginal decade better, all the decades that come before it by necessity have to be good. You can't just wake up one day at 86 and say, "The next 10 years are gonna be amazing," if they're not already really amazing at 86, which means they were very good at 76 and 66, et cetera. And so if I haven't lost you yet with this idea that the marginal decade is the last decade of your life,

  6. 13:00 – 16:02

    The Centenarian Decathlon: training (not just exercising) for the abilities you’ll want at 90+

    1. PA

      you don't know the day you enter it, but you will all have one. Hopefully no one in this room is in their marginal decade, um, but we're all gonna be there. Uh, and we want that decade to be as far away as possible. The, the next idea is, uh, one that comes really from my love of sports, which is that, um, no matter what athlete you're talking about, none of them are exercising. You might say, "What are you talking about? Athletes exercise all the time." No. Athletes train. There's a fundamental difference. Exercise is just kinetic. It's just movement, right? Going for a run, jumping up and down, great, that's exercise. Training is specificity. And this is why if you pick the best athlete in every sport, they look nothing alike, their training looks nothing alike, and they are not shufflable, right? You could not put Max Verstappen on a basketball court. You cannot put Steph Curry in a car. You cannot put Patrick Mahomes in, you know, uh, in a different position, let alone a different sport. That's specificity. And I realized that, well, that must be the way we think about the marginal decade. We have to make life our sport. Because we know that exercise is beneficial, and if you did nothing but mindlessly exercise, run and lift weights and do all these things, that's great. You will get many of the lifespan benefits of exercise, which is to say your risk of heart disease and cancer, dementia, metabolic disease will go down. You won't necessarily get the healthspan benefits because, for example, you could injure yourself. Well, that's very counterproductive. If you're running to the point where you're grinding your knees into the ground, you're gonna have a hard time being mobile in the final decade of your life. And so if instead we focus on this idea that I call the centenarian decathlon, which just means you pick the 10 most important things you wanna physically be able to do in the last decade of your life, and these can be both recreational activities, but also just activities of daily living. I get asked all the time like, "Tell me some of the things your patients say." I mean, on the activities of daily living side, it's have sex, uh, care for myself, be able to cook. Like, it's things that we would all just take for granted today. And then of course, people also think about what they wanna be able to do recreationally. A lot of people say, "Look, I really enjoy playing golf. If I'm 90, could I play 18 holes and actually walk all 18? Uh, could I pick a kid up, a grandchild out of a crib? Uh, can I sit on the floor and get up on my own?" Again, all of us could do these things today without any effort, but if you've been around people in the final decade of their life, very few of them can do these things. Well, I would argue it's because none of that will happen automatically, and the only way it will happen is if you train for those things as though they are the sport. And it's just weird 'cause we don't think of people in their 90s competing in the Olympics, but that's effectively what it is.

    2. TS

      [laughs]

  7. 16:02 – 17:42

    Strategy vs. tactics: five “pillars” for practicing longevity

    1. TS

      Great. Thanks for that. Um, so, so let's move a little bit into how people can put this into practice in their lives. Uh, in the book, you, uh, quote Sun Tzu saying that, "Tactics without strategy is noise before the defeat." Could you talk a little bit about that and then maybe expand on what are some of the tactics that can help people to sort of achieve their centenarian decathlon?

    2. PA

      Hmm. Well, you know, we sort of break, um, we, we break the tactics down into kind of five areas, domains, pillars, whatever you wanna call them. Um, so I think... And, and there... You, you could argue there's a sixth one that is all else, just to make it sort of mutually exclusive and collectively exhaustive. But-

    3. TS

      [laughs]

    4. PA

      ... uh, nutrition would clearly be something that fits in. Like, it's a, it's a clear input that matters in this equation.

    5. TS

      And that's your favorite topic.

    6. PA

      Yeah, that's the one I wanna talk about exclusively. Um, then we have exercise, [clears throat] which actually is my favorite topic. Um, sleep. Uh, all the tools that we would think of bringing towards emotional health and happiness. And then, uh, the fifth one that I talk about is molecules. Uh, uh, exogenous molecules, meaning anything that you take from the outside that put in that's not food. So drugs or supplements or hormones. And, and like I said, I guess if you really want it to be MECE, you would add a sixth bucket and just call it the waste bin of everything else, some of which is probably valuable like saunas, some of which is probably useless like hyperbaric oxygen. Sorry if people love hyperbaric-

    7. TS

      [laughs]

    8. PA

      ... oxygen chambers. Um, but, but you could just say, "And every other thing that anybody thinks of."

    9. TS

      Okay.

    10. PA

      Yeah.

    11. TS

      Great. Um, so maybe I'll go to nutrition first, since you-

    12. PA

      Perfect

    13. TS

      ... don't like it. So-

    14. PA

      [laughs]

    15. TS

      [laughs]

  8. 17:42 – 21:27

    Nutrition simplified: energy balance and prioritizing protein

    1. TS

      It's a topic you often joke about not, uh, loving to speak about. But what are just some common misconceptions that people have about nutrition, and what do you think are sort of the no regret moves?

    2. PA

      I think the biggest misconception about nutrition is that it's more complicated than it is.

    3. TS

      Mm-hmm.

    4. PA

      And that there's one true diet and that... And this, by the way, this isn't... This is kind of an elitist view of nutrition. I don't think the average person out there is, is thinking this way. But, but I think that in the circle of, you know, influencers and personalities and things, there's this view that like My diet is the diet, and those of you that are eating seed oils or eating this or eating that, I mean, you're, you're... I mean, gosh, you might as well be smoking.

    5. TS

      [laughs]

    6. PA

      So, so the, the truth of it is [clears throat] the human body is remarkably resilient at basically turning chemical energy into electrical energy back to chemical energy. That's all we're doing. We're just taking hydrocarbons, we're breaking them down, stealing the electrons, putting them into the mitochondria, generating ATP from ADP, and recycling, re- re- recycling the whole thing. And, um, so there's a little bit of kind of religion that flows into this. Because it is so cultural, because it is so relevant, we just really wanna believe that what we're doing is the right thing. But the truth of it is, the, the things that are capital T true are that energy balance matters a lot.

    7. TS

      Mm.

    8. PA

      Meaning you can't eat too much, and you can't eat too little. Now, the body has way more protections against the eating too little part. This is an obvious if you reflect on our evolutionary history, right? Too little food was historically a way, way bigger problem than too much food. Too much food has only been a problem for 50 years, and 50 years out of 250,000 as Homo sapiens is nothing. 50 years out of billions of years as going back to single-celled organisms is also nothing. So, so we have zero evolutionary adaptations for too much food, but we have lots for too little food. So neither is good, but they're bad for different reasons, and our system is skewed to tolerate, uh, excess more than deficiency. Um, another important principle is that of the three macronutrients, the one that you ought to pay most attention to is protein. Not carbs, not fat. Carbs and fat can be quite fungible. They're both great sources of energy. Fats are more essential because you need them for structural purposes, so you can't be too restrictive on fats. But there's actually quite a bit of flex in the system how much you wanna toggle between your fat and your carb buttons. But where you don't wanna get too out of whack is on protein, and the reason is protein is purely structural. So it is the building block for muscles, it's the building block for enzymes, it's the building block for many of the very important things in our body. So protein deficiency is really bad, and th- we know this, for example, like the body will go to such amazing lengths during starvation to preserve muscle mass until the very end. And, um, and obviously, once a person is in starvation and they're starting to consume muscle mass, the end is very close. So [clears throat]

    9. TS

      [clears throat]

    10. PA

      Beyond those things of how much you're eating in total calories, which will be reflected, I'm sure, if we talk about metabolic health and what are the consequences of excess calories, um, and getting sufficient protein, i- if you, if, if there's truly an 80/20 rule, that's the 80.

  9. 21:27 – 24:42

    Why exercise dominates the impact on lifespan and healthspan: VO2 max and strength as outputs

    1. TS

      Yeah. Got it. Thanks. [clears throat] Um, so let's talk about exercise since you do love that. Uh, explain sort of just the importance of cardiovascular strength, mobility. You touch on all these things, uh, in the book, and just how do they contribute to staving off the Four Horsemen and just contributing to healthspan?

    2. PA

      So I think it's important to just sort of acknowledge that the, the... I don't harp on exercise just because I enjoy it, although I do. I think the data make it pretty clear-

    3. TS

      Mm-hmm

    4. PA

      ... that exercise has a bigger impact on length and quality of life than any of the other metrics. And the easiest way, I think, to look at this is to look at what happens when a person is in the off state-

    5. TS

      Mm-hmm

    6. PA

      ... for a given input, right? So what's the off state for nutrition? What would be a good place we could look for the off state of nutrition? It would probably be either, um, uh, significant obesity or type 2 diabetes. Those would be the two most extreme states. You could say malnutrition, but I'm putting that aside. That's not really a problem today. Would've been a problem before, and, and obviously it's a problem in certain part of the world. But let's just, for the purpose of this illustration, say what is the increase in all-cause mortality for a person with type 2 diabetes? Uh, and it's significant. Um, so how significant? It's about 40%. That's a big number. That means that at any given point in time, a person with type 2 diabetes has an increase in all-cause mortality for the coming year of 40% more than the similar person, age, sex, education, smoking status, et cetera, that the non-diabetic person does. So it's a very big deal. Um, so we put that number aside, and now we go and do the same analysis with other variables that are congruent with exercise. Notice not with exercise because that becomes... It's irrelevant to look at inputs and subjective as- assessments of, like, what I do. In other words, I don't care what people tell me they eat. I care about the end state. I don't care what people say about how much they exercise. I care about the end state. How strong are you, and what's your VO2 max? Those are the two most objective ways that we can measure the output as opposed to the input. Does that make sense? I don't care about the inputs because there's no reliability in reporting that stuff. I just care about objective measurements on the output. So I can measure your VO2 max. I can measure how strong you are. Those are very objective. And the data there is overwhelming. If you compare top quartile VO2 max to bottom quartile VO2 max, it's 175% difference in all-cause mortality. If you measure top decile strength or even top- Uh, quintile strength to bottom quintile strength, you're talking about a 100 to 125% difference in all-cause mortality. So we have to discount all of these things because they're associative, and they're not randomized data, so there's a healthy user bias embedded within them. But when you're starting to talk about, um, hazard ratios that are that large, you know that there's actually a signal there, and it's not just a bunch of random noise like, oh, you know, people who eat pepperoni have a 6% -

    7. TS

      [laughs]

    8. PA

      ... greater chance of colon cancer. That's the noise you can totally tune out.

  10. 24:42 – 28:28

    Supplements framework: deficiency vs. super-normal targets, mechanisms, safety, and risk/reward

    1. TS

      Yeah. [laughs] Thanks for that. Um, I think we'll skip over sleep. You've got a, a lot of great podcasts and things like that on, on that subject. But on supplements, um, I think people are kinda confused, right? There's industry and influencers that are constantly peddling quick fixes and whatnot. H- how do people sort through the noise and understand, A, do they even need supplements, and B, which ones are right for them?

    2. PA

      So I really like frameworks because, um, people always want me to give an answer, but I feel like if you, you know, n- it's such a stupid cliché, but, like, if you just give a person the answer, you're kinda giving them the fish. But if you give them the framework, you're teaching them how to fish kinda thing. So I would say, given that there is no shortage of supplements on the market today, and there will never be a shortage of them in the, in perpetuity, it's better to think of it this way. So when I'm ... Anytime someone asks me about a supplement, and a- again, let's just say a patient coming into the practice, what am I, what am I asking? I'm saying, "Okay, question one, is this a supplement you are taking to replete, replace, correct a deficit, or are we talking about something that is independent of that, and we're dealing with super normal physiologic levels?" So an example would be vitamin D. Someone says, "Should I be taking vitamin D?" Well, again, are you taking it because your vitamin D levels, which we can objectively measure, are low, and you're replacing it? Yes or no. Um, but for many supplements, the answer to that question is no, we're, we're not repleting, uh, replacing something physiologic. We're, we're, we're taking something that is, uh, you know, outside of the realms of that. Creatine would be an example, right? Should you be taking creatine every day? Well, again, you're clearly taking more than the body normally would take in. Second question then is, are you taking this because you believe it will positively impact lifespan or healthspan? If lifespan, is it doing it through a specific mechanism that targets a specific disease?

    3. TS

      Mm.

    4. PA

      For example-

    5. TS

      Mm

    6. PA

      ... I'm taking this supplement because I believe it will lower my risk of cardiovascular disease, which is a cause of mortality, so that should increase lifespan. Um, or are you taking this because, meh, it might not have any, uh, bearing on any disease, but it might improve my quality of life, to which I then say, "Okay, bracket it as physical, cognitive, emotional."

    7. TS

      Mm-hmm.

    8. PA

      The next question is, do we know the mechanism of action? Again, you don't have to get the quote unquote right answer to each of these questions, but if you go through this, it becomes really easy at the end to go, "This is probably nonsense." The next question is, what are the safety data? What do I know about the production of this actual molecule, and how has it tested in animals and in humans? Uh, and how sure can I be about its purity? Because again-

    9. TS

      Mm

    10. PA

      ... the problem with supplements is they're not regulated. So there can be anything in a bottle. There is no regulatory oversight. So you are putting an unbelievable amount of faith in a company that has no reason to ... They're, even if they're not trying to harm you, they have no reason, um, to, to sort of toe the line that, for example, a drug company does. And then lastly, how do you put this all together in a risk/reward matrix of trade-off, right? Where you assess the certainty by which you think the efficacy is there, the safety is there. And honestly, I think when you go through this logic, you realize there aren't ... The list of supplements that a person should noodle taking is pretty, pretty low.

  11. 28:28 – 32:52

    Data vs. intuition: using measurements without letting wearables mislead you

    1. TS

      Mm. Great. Thanks. Um, so as you think about these tactics and the fact that you talked about output being important, a lot of this is very measurable. Blood tests, you know, devices that we wear, things like that. Um, so in this field that's, like, sort of increasingly dominated by data, how do you m- balance taking in all this data with just intuition and how you feel?

    2. PA

      Yeah, that's, that's a great question, and, and it's, I think it's different for different people.

    3. TS

      Mm-hmm.

    4. PA

      Like, I guess because I'm an engineer, I actually like data.

    5. TS

      Yeah.

    6. PA

      Um, I don't mind it. I don't get overwhelmed by it. I, I, it sounds silly, but I, I would bet that half this room can appreciate this, like, it's just fun. Like-

    7. TS

      [laughs]

    8. PA

      ... I like spreadsheets.

    9. TS

      [laughs]

    10. PA

      I like Excel more than I like PowerPoint and Word.

    11. TS

      [laughs]

    12. PA

      That's just the way it is. It's always gonna be that way. And, um, and therefore I, I really enjoy modeling things, and I love coming home from a ride and downloading the data and looking at it. But if there's someone in this room who's listening who says, "What the hell are you talking about?"

    13. TS

      [laughs]

    14. PA

      That's totally fine. You don't need to do any of that nonsense. Sometimes there are certain things where if you once in a while pay attention to it, it will help guide you.

    15. TS

      Mm.

    16. PA

      So for example, there's a type of exercise that I talk about as being very important. It's called zone 2 cardio training. So when you're ... We all understand, I think, that cardio training is important, but it has to be done at different intensity levels, and there's a low energy system, um, that we describe as zone 2, and there's a very technical definition to explain what it means, and it has to do with the way the mitochondria is working. But most people don't care. They just wanna know, how intense should I be exercising to hit that level? Well- If you're me, you actually every single day check your lactate levels while you're doing the workouts by poking yourself in the finger to get that number.

    17. TS

      [laughs]

    18. PA

      But very few of my patients do that, and nor do I care that they do it or want them to do it.

    19. TS

      Yeah.

    20. PA

      But I do care that they know if they're in zone 2. So at the other end of the spectrum, [clears throat] if you're not willing to use the gold standard, which is measuring lactate, and you don't even really wanna get crazy about wearing a heart rate monitor, which would be sort of the next way to help do it, you can just rely on what's called the rate of perceived exertion. And if you don't wanna learn the Borg scale, which is fine, you can just do something very simple, which is, am I able to speak while I'm doing this, albeit difficultly?

    21. TS

      Yeah.

    22. PA

      Great. If the answer is you can talk, you just don't wanna talk, but you can talk in a complete sentence, you're in zone 2. If you can't talk in a complete sentence, you're in zone 3 or 4.

    23. TS

      Mm.

    24. PA

      If you can talk and it's quite easy, you're in zone 1. So that becomes a really simple way. And honestly, I think you can do this for so many things. Um, and I, I think that, um, you know, like for example, wearables for sleep are very popular. Are they necessary? No, I don't think they're necessary at all, and I think frankly, they can cause a lot of anxiety for people, especially when the data are wrong, which depending on the wearable, they're wrong quite a bit.

    25. TS

      Mm-hmm.

    26. PA

      Um, and so people will wake up and they'll be like, "I feel fine." And then they'll look at their sleep data and they'll be like-

    27. TS

      [laughs]

    28. PA

      ... "Oh my God, I, I didn't get good sleep last night."

    29. TS

      [laughs]

    30. PA

      And, um, you know, I'll, I'll... I mean, I, I interviewed a guy by the name of Tadej Pogačar. I don't know if any of you know who Tadej is. So-

  12. 32:52 – 38:25

    Life trade-offs and the emotional core: family, time scarcity, and improving emotional health with age

    1. TS

      Got it. Thanks. So, um, you're a busy guy. You're a, you know, a husband, father, physician, podcaster, writer, entrepreneur, all these things.

    2. PA

      [clears throat]

    3. TS

      Um, and, and lots of people watching and here in the room today go through seasons of life. So what are the elements that are sort of the non-negotiables, and when can you, you know, flex to allow for that season of life to prioritize other things that may, you know, arise? New baby, new job, new health diagnosis, et cetera.

    4. PA

      I would really like another baby, but my wife has said no.

    5. TS

      [laughs]

    6. PA

      So unfortunately we're, we're down to our... We, we have three, but, um-

    7. TS

      [laughs]

    8. PA

      I think, um, I think this is difficult. I don't pretend to have a great insight here, honestly. I think this is kind of the eternal struggle. Um, I think the, I think the cruelest thing about being a human is that we, we can't... You know how you can discount cash flows, right? You know how you can sort of... You can conceptually treat money in the future as less valuable than money today? We can't do the following exercise. I can't say I'm 51 today. From now until I'm 61, two things are simultaneously true, and I wish I could switch them. So unfortunately, the next decade of my life is the most productive decade of my life to work. That's just the nature of the fact that, you know, my brain still works. Uh, my work is relevant. You know, all the reasons that anybody would feel that, like, this is still a, a good time to be in my career. Uh, it's also the most important decade when my kids are in the house.

    9. TS

      Mm.

    10. PA

      I have three kids in the house, and for the next 10 years, at least one of them will be in the house. So I really wish I could work 30 or 40 hours a week for the next 10 years, and then when they all leave, go back to working 60 hours a week.

    11. TS

      Mm.

    12. PA

      But it doesn't really work that way, 'cause in 10 years nobody's gonna know who I am, and I'm gonna be irrelevant, and I could do all the work in the world I want, it's not gonna matter. Like-

    13. TS

      [laughs]

    14. PA

      ... I... This is the only opportunity I have to do this, and I'm sure many people can kinda relate to that. But I don't just wanna kill myself and do 80 hours a week, even though I'm physically capable of it. Because when my kids are gone, as you probably all know, there's a statistic that, uh-

    15. TS

      Yeah

    16. PA

      ... children will spend 19 years on average in the company of their parents, and the first 18 of those 19 years are the first 18 years of their life. So once they go to college, you get a grand total of 365 days with your kids as adults. That statistic terrifies the hell out of me, and honestly, it's the greatest tension in my life. Which is, there's a part of me that literally wants to do nothing but play baseball and chess-

    17. TS

      Mm-hmm

    18. PA

      ... with my boys and ride bikes and play soccer and goof off. Like, I, I could literally just do that all day, but I can't. So how do I balance it? And I, I don't, I don't know the answer, other than I feel like at least by knowing that and being aware of it, I'm doing a better job than I used to five years ago.

    19. TS

      Yeah. That's great. And maybe we'll pull on that thread a little bit and talk about emotional health. So, um, in the book you share a personal story about, you know, the importance of emotional health and how while we age, physical and cognitive abilities are just destined to decline, but, uh, as we get older, we can actually improve our emotional health. Can you talk a little bit about just the subject?

    20. PA

      Yeah. I mean, I think it's a difficult subject to talk about because, you know, it, it, now we get so far outside of my... I have no professional experience, right? So I can talk about exercise, I can talk about cardiovascular disease, talk about these things, and I, I can speak to them outside- My sphere of, of, uh, experience. But when I talk about this, I'm, I'm mostly just talking about myself and, and obviously what I've learned from my patients. Um, but it is true, and I think that's, that's, that's even for people like myself who struggle with mortality, which I do. I... If, if I think about it a lot, it's still a struggle. It's still hard to wrap my mind around the finitude of life.

    21. TS

      Mm.

    22. PA

      Um, and it's... On the one hand, I feel like how lucky are any of us to exist, right? Just statistically speaking, no one should be here. And then the fact that we actually exist now as opposed to 500 years ago, 5,000 years ago, 50,000 years ago, I mean, that's insane. Oh, and then the fact that we exist in the United States or in the developed world as opposed to Sub-Saharan Africa, like, I mean, that's insane. So you have, you have all of these things that are incredible, and yet somehow we still feel robbed by the fact that we don't get to live forever. And this is... You can appreciate this in the zeitgeist, right? This do not die. We cannot die. We must be immortal. Uh, I mean, uh, we... all of us struggle with this one way or the other. But if you then come back to reality, you realize, well, you know, barring some miracle, and maybe we can talk about what some of those miracles might be, um, our healthspan physically and cognitively slows.

    23. TS

      Mm-hmm.

    24. PA

      I mean, I'm... It's... They've already slowed so much for me that it's frustrating.

    25. TS

      Mm.

    26. PA

      Um, but to think that this other one area doesn't have to, where your relationships with others, your relationship with yourself can actually get better as you age, kind of like wine-

    27. TS

      Mm-hmm

    28. PA

      ... that to me is both hopeful, but also gives motivation to work on that thing just as we would work on delaying the decline of the other things.

  13. 38:25 – 40:15

    Deliberate wisdom: introspection, self-honesty, and not relying on luck

    1. TS

      Yeah. So can you share a little bit more about, you know, you've, you've been studying the field of longevity for quite some time. Can you just share a little bit about, like, wisdom and aging and how you think, you know, age enriches one's life?

    2. PA

      Well, I don't think that's necessarily or automatically the case, right? I mean, I think that for some people it probably is, but I think for other people it has to be somewhat deliberate. And I guess that's sort of my argument with the Centenarian Decathlon, which is every once in a while you'll come across the story of a person who's 100 years old, and they're as spry as a 75-year-old, and we're like, "What's your secret? What's your secret?" And but a lot of the times is there's no secret. It's luck. Like, there's gonna be outliers [laughs] out there.

    3. TS

      [laughs]

    4. PA

      Um, so, so, so luck is not a strategy. Um, so preparation is the strategy, and therefore I don't draw a lot of inspiration from the people who just got there by luck. I, I kind of look at the people who had to overcome something to get there physically, emotionally, whatever. Um, look, I think the single most important thing is just introspection. Like, if you cannot be honest with yourself about your shortcomings, y- y- you're never going to grow.

    5. TS

      Mm.

    6. PA

      I mean, that's, that's just full stop all day. When I... You know, if I think about the single biggest impediment to happiness in a person's life, it's when they can't acknowledge their own mistakes, they can't acknowledge how their actions are impacting other people. Th- there's... Until that changes, you, you, you can't begin to kind of, um, create a new pattern of behavior.

    7. TS

      Yeah. There's a phrase that we use that, you know, the best leader is the self-aware leader. So it's just an element of self-awareness, it sounds like-

  14. 40:15 – 44:47

    Changing his mind: metformin, GLP-1 drugs, and the economics of access

    1. PA

      Yeah

    2. TS

      ... and introspection. Um, it's, uh, kind of building on that, o- one of the things that I think people really admire about you is that you're not afraid to sort of change your mind on subjects that you've studied and maybe held an opinion about, and then you, you go back on it. Um, I know the book took you quite some time to... It almost didn't even come to, to life. We're glad that it did. But are there any practices or insights that you didn't include in the book or that have changed since you've written it?

    3. PA

      Yes, many. Um, where to begin?

    4. TS

      [laughs]

    5. PA

      How long do we have?

    6. TS

      [laughs]

    7. PA

      Um, I would say, I mean, just, just on the, on the pharma side, um, I think two, two things that, um, I've changed my mind on quite a bit. Um, I used to have a pretty negative view on metformin in, um, modestly healthy people who were exercising.

    8. TS

      Oh.

    9. PA

      So someone with a little bit of insulin resistance, usually measured by, you know, higher levels of fasting glucose.

    10. TS

      Mm-hmm.

    11. PA

      So high... If your glucose is high in the morning, the only place it came from is the liver, right? You haven't eaten in 10 hours. Your muscles can't put any in the circulation. So if your glucose in the morning is 110 milligrams per deciliter, that is a hepatic glucose output problem. And there's one drug that treats that really well, and it's called metformin. But I've always had the view that, well, metformin, because it, it, um, it inhibits w- part of the mitochondria, and that's how it activates, uh... Well, d- we don't have to get into all that.

    12. TS

      Mm-hmm.

    13. PA

      But I've always thought, well, not a great idea. I also know that we see a slight increase in serum lactate levels in people taking metformin even when they're not exercising. I just thought that, you know, it was doing something in the muscle that I didn't like. And actually I recently learned that no, that's not true. I looked at a tracer study and realized that, um, that metformin can only get taken up into cells through something called an organic cation transporter, and it only exists in the liver.

    14. TS

      Mm.

    15. PA

      So all of that lactate elevation we're seeing is in the liver, not in the muscle. Not, it's not from muscle production of lactate. And so that's a silly and small example, but it is an example of where I am more liberal now with the use of metformin. Um, a more topical discussion might be around the use of GLP-1As.

    16. TS

      Mm.

    17. PA

      So again, when these drugs came out 10 years ago... Actually, um, the second generation one came out 10 years ago. That was when I first learned about them. Um, I didn't think much of them, and they quite frankly didn't have much efficacy for weight loss. It wasn't until four years ago that the diabetes data for semaglutide showed how effective they were for weight loss, um, and we began to start using them sparingly in patients. And I was still a little bit skeptical, uh, which I don't think is a problem. I think it's good to be spec- skeptical. But, um, I really just felt like, one, it wasn't possible to maintain muscle mass while you were on these things, and two, there were a bunch of other things that I thought would be negative side effects. But I, I just think with the emergence of more and more data, and now that we're seeing generation f- uh, generation five data, so the fifth version of this that's not out yet, um, the data look better and better and better, and I'm really believing we are... This is a major turning point in, um, in how we think about metabolic disease. And now frankly, to me, it's not even a que- It, now it's just a question of economics.

    18. TS

      Yeah.

    19. PA

      Now it's just a question of, can we tear down the PBMs and get rid of them altogether-

    20. TS

      Yeah

    21. PA

      ... so that Americans don't have to get gouged on the price? Because the truth of it is, guys, a monthly supply of tirzepatide is 300 bucks. So when a patient pays 1,000, 700 of that is going to their employer-

    22. TS

      Wow

    23. PA

      ... through the PBM and a cash rebate. I want every American to understand that.

    24. TS

      Mm.

    25. PA

      This, if, if I'm gonna die on a cross one day, it's that cross. I want the American public-

    26. TS

      [laughs]

    27. PA

      ... to understand how corrupt the PBMs are and how they are literally stealing money from American workers to cross-subsidize back to drug companies and to their employers. So, um, people say, "Well, these drugs are so expensive. We're never gonna be able to manage the 42% obesity rate at that price point," and you're right. At that price point, we can't. But if we actually paid what everyone else in the world pays for them without our, um, bureaucracy around, um, uh, this system, I, I think we start to have better opportunity.

  15. 44:47 – 49:53

    Obesity and metabolic disease at societal scale: multiple drivers, limits of policy, and a combined approach

    1. TS

      Yeah. Um, I promised a question on just metabolic health, and I think that's a good sort of entrance into it. So there was a study published last week, I know we always have to take these things with a grain of salt, but it effectively suggested that obesity is just at a crisis point, uh, in the US, and that the, the disease burden associated with that is just massive on our society. What sort of like cultural or societal shifts do you think need to take place to help address this?

    2. PA

      Well, you could, [laughs] you could sort of think about that question in many ways, right? The, the, the, the first way you can think about that is the why. Like, what changed so much in the last 50 years that the rate of obesity has gone from roughly 10% to 40% and type 2 diabetes has gone from 1% to 10%?

    3. TS

      Mm-hmm.

    4. PA

      By the way, that's a more startling statistic, uh, is the log fold increase in type 2 diabetes in the last decade. Um, and I suspect the reason that w- there's so much debate around this is that it's not one thing, and that when we, when you, when you have many things that are conspiring against you, um, you're always going to have different arguments for, well, it's, it's all, uh, big ag. Like, it's-

    5. TS

      Mm

    6. PA

      ... you know, it's the glyphosate in the, in the wheat, or it's the sugar, or it's the, uh, electronics, or it's, you know, the hyperpalatability of food, or the fat or the salt, um, the inactivity, the stress, the reduction in sleep. And the truth of it is it's probably all of the above, and you need three of the eight to sort of kick you off on the wrong path. Like, I, I'm making this up, right?

    7. TS

      Yeah.

    8. PA

      But you can imagine a model where, okay, there were 10 potential things out there that trigger obesity and diabetes, and once you accumulate three or four of them, you're m- 80% of people are on the way there genetically. And, um, and in a system like that, it's very difficult to identify and then target from a policy perspective what you're going to do about it. Um, but like I... It's not clear to me that even if you took some of the most egregious offenders, like if you just taxed sugar, would this get better? I think the answer is no, it wouldn't. Like, I just don't... I'm not, I'm not convinced that any sort of, uh, solution like that's going to work. So, um, I c- I can certainly imagine scenarios where if you had perfect control over a population in an autocratic world, you could, you could make draconian changes that would impact it. But-

    9. TS

      Mm

    10. PA

      ... that's just not even a trade-off that's even worth talking about, because nobody wants to deal with what the other consequences of that are. So one of the most remarkable things about being in the United States is that we're a consumerist society. Like, we, we, we c- we want it bigger, we want it faster, we want it now, we want the best, we want... Well, okay, that comes at a cost.

    11. TS

      Yeah.

    12. PA

      Um, and anybody who's been to other parts of the world where you don't see the same obesity rates realize it's a totally different culture. A totally different culture. So it sounds like a cop-out answer, but it's the same reason why US healthcare is twice as expensive as everyone else's. It really comes down to the fact that we are the greatest consumers on Earth.

    13. TS

      Yeah.

    14. PA

      Now, again, the question is, what can we do about it, or what should we do about it? And I think the answer is we should do something about it, because it's... If you're not swayed by the economic cost of it, which is significant, you should be swayed maybe by the personal cost of it.

    15. TS

      Mm.

    16. PA

      Um, and I think the personal cost is high. I think the suffering is, is real. Uh, and I kind of reject this idea that obese people are just gluttons and sloths. Like, I, I think that's just such a dumb argument. Um, and I, I just don't think anybody wakes up and says, "What can I do today to be more overweight? Like, I, I'd really like to double down on my type 2 diabetes. How can I do it?"

    17. TS

      [laughs]

    18. PA

      A- and maybe this is getting a little too philosophical, but I also kind of reject the willpower argument a little bit. I also think that's a little bit genetic. I, I mean, that's a very unpopular thing to say among high-achieving individuals, but, like, everybody says, "God, Peter, you have insane willpower." And it's like, yeah, but I don't think I did anything to get it. Like, it, it was... It's carved into my chip. Like-

    19. TS

      Mm-hmm

    20. PA

      ... that, that's... The chip was built that way. So, uh, it's very difficult for someone who's got that chip set to look at the other person and sort of say, "Why aren't you like this?" Um, so, so all of this is to say I'm very excited about these pharmacologic options, and I think they should be a part of a solution, but I also think people should be exercising more and eating better because I think they will feel better, and I think they will perform better, and I think they will enjoy their lives more. So I'd like to kind of see the whole thing done. Um, but it's, it's... That's not a, that's not an easy thing to do 'cause it's part policy, part culture, uh, part structure.

  16. 49:53 – 1:00:37

    Audience Q&A: AI in healthcare, health-system reform, autoimmunity treatments, and peptide regulation

    1. TS

      Yeah. Thanks. Um, okay, we're gonna move to Q&A 'cause we have about 10 minutes left, and, uh, we had some, uh, questions submitted from online. So I'm gonna read one of those first, and then we'll move to live questions in the room. So Brent from Dallas asks, uh, "Given AI's potential to transform healthcare in many ways, from drug discovery to patient care and access, what do you see as AI's biggest potential to change the way that practitioners transition to Medicine 3.0, and what can companies like Google do to accelerate this process?"

    2. PA

      Oh, that's a, that's a tougher question than the one I hoped you were gonna ask-

    3. TS

      [laughs]

    4. PA

      ... which is where, where is AI gonna help medicine?

    5. TS

      Yeah.

    6. PA

      Um... But that said, you know what? The way to help practitioners transition to 3.0 is get a bunch of the 2.0 stuff off their plate.

    7. TS

      Mm.

    8. PA

      So I think there are, um, there are a couple of big areas where, where AI can and should help pr- practitioners today. So the adminis- do any of you married to physicians and listen, have to listen to them gripe about it over dinner?

    9. TS

      [laughs]

    10. PA

      Yeah. A- and again, this is not something I deal with because we're in a private practice. We don't take insurance. We're not dealing with it. But, but if you're in the system that most doctors are in, y- the administrative burden of your job is generally regarded as the most unrewarding aspect of the profession. And the, the... Something that started out as, "Hey, this is good," the EMR, like, "This is gonna make medicine better," um, has become so onerous and so user-hostile that most doctors who are still in this system of, "Hey, this is what I do. I, I have 11 minutes to see 40 patients of each," you know, um, they're getting mired down in, in sort of the charting aspect of this. Then you layer on top of that the, the reconciliation and adjudication of charges. Remember, there's something in the United States healthcare system that is just hard to fathom. It's not just that it's a $4.5 trillion system, if you can just wrap your head around that for a moment.

    11. TS

      Wow.

    12. PA

      It's that 15% of that $4.5 trillion is purely administrative friction. There's no other healthcare system in the world, because they're all single-payer systems, that has to have a 15% friction tax. That's the first thing AI should be solving.

    13. TS

      Mm.

    14. PA

      There's no value being created there. There's no patient life that's being made better, physician experience that's being made better. Um, so even though that's not sexy... We love to talk about folding proteins, and that is super cool.

    15. TS

      [laughs]

    16. PA

      Um, and that will shorten the path to drug discovery. But take 15% of the cost of healthcare away by taking the friction and brain damage away of reconciliation, adjudication, charting, that would be huge. I think another place where I hope AI can be really helpful, and this isn't necessarily going to impact physicians, is, um, we do have to come up with a better way to do not just drug discovery but drug testing.

    17. TS

      Mm.

    18. PA

      Um, we have to come up with better biomarkers that can predict success in late-stage drugs 'cause if you, if you look at AlphaFold, right, it's pretty amazing in that you're gonna get to an IND quicker than you would've before, but then guess what? You still have to do phase one, phase two, phase three. That's still more than a billion dollars and 10 years.

    19. TS

      Wow.

    20. PA

      So to shortcut that and increase the probability of success there, you have to be able to predict in phase one success in phase three better. And, and we, we right now are- have such poor biomarkers for nuanced things, right? We, we cannot measure senescence. We can't measure mTOR activity. There's a whole bunch of stuff. We just have no clue what's going on, and therefore we, we're not even trying to develop drugs that would target those systems. Um, I could go on, but I think those are just two opposite end examples from the totally banal to the totally sci-fi.

    21. TS

      Great. [laughs] Thanks for that. All right, so we will take a few questions from the room. Um, and for purposes of the recording, I'll repeat the question before you answer. Thanks.

    22. TS

      We have one over here.

    23. TS

      Thank you for the book. I think you have us all eating more protein and working on strength training.

    24. PA

      [laughs]

    25. TS

      Um, my question was, uh, not to get too political, but obviously we have a, um, someone who's been nominated for the health secretary, uh, has some interesting ideas and more controversial. If you were to be nominated, like, what were, like, the two or three things that you would wanna focus on to help make this country, um, he- healthier again? Can I repeat the question?

    26. PA

      Sure.

    27. TS

      Okay, great. Thanks. So the question is, uh, if Peter were to be nominated to, uh, a government position where he could sort of wave a wand and, uh, make change happen and make us all healthier, what would that look like?

    28. PA

      Well, I think the wand waving would be putting me in that position.

    29. TS

      [laughs]

    30. TS

      [laughs]

Episode duration: 1:00:42

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