Plain English with Derek Thompson - Is Radical Human Life Extension Possible?

Episode Date: October 18, 2024

In 1900, the average US life expectancy was 47 years old. That's the current age of Tom Brady, Ryan Reynolds, and Shakira. But extraordinary advances in medicine and public health have surged lifespans in the US and throughout the world. The average American currently lives to about 79 years old. How long can this progress continue? As we have gotten so much better at allowing people to live to old age, how much progress have we made at confronting this ultimate boss of longevity? Today’s guest is Professor S. Jay Olshansky, from the school of public health at the University of Illinois at Chicago. We talk about progress and stasis in the most important science project in human history: how to increase human life. If you have questions, observations, or ideas for future episodes, email us at [e-mail]. Host: Derek Thompson Guest: S. Jay Olshansky Producer: Devon Baroldi LINKS: "Implausibility of radical life extension in humans in the twenty-first century" [link] "If Humans Were Built to Last," an illustration of what people would look like if they were optimally designed to live to 100 [link] "Child and Infant Mortality," from Our World in Data [link] Learn more about your ad choices. Visit podcastchoices.com/adchoices

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If you ask me, what is the single most hopeful picture on the internet? I would direct your attention to the website, Our World in Data, and the page with the inauspicious title, Child and Infant Mortality. For most of human history, half of the human population, died before reaching the age of 15. Just about every civilization for which we have data seems to hover around this coin flip line. In ancient Rome, 50% of children died before turning 15.

In the France of Louis XIV, the child mortality rate was also 50%. But since the 1800s, child mortality has plummeted around the world. Today in countries like Iceland, Finland, and Japan, the number has fallen to 0.3%. By this all-important metric, the present is not just a little bit better than the past, it is 150 times better than the past. Again, I think you could plausibly argue that there is no happier statistic in the universe. In the last 200 years, human lifespans of sword as a result of reductions in infant mortality. advances in sanitation and medicine.

Overall, in America, life expectancy has gone from 47 in 1900 to 79 today. 47 in 1900. Tom Brady is 47. Ryan Reynolds is 47. Shakira is 47. In 124 years, we've gained 32 years of life. Again, this is absolutely remarkable. But will it continue?

If it does, we should be prepared for a surge of centenarians, people living to 100 and long past that. In 2001, Stephen Austed, a professor of biology at the University of Alabama at Birmingham, was asked at a meeting of scientists when he thought the first person to live to 150 would be born. I think that person is already alive, Stephen said. But there was another scientist, S. J. Olshanski, who heard this comment, and bet Osteed that it would never happen. That was 20 years ago. And what we've seen in the last 20 years suggests that J. Olshansky might be right. If you recall, in 1997, Jean Calman, a French woman, said to be 122 years old, set the world record for oldest verified age at death. In sharp contrast, the furious pace of longevity progress that I just described to you, that record has stood for 27 years.

There is nobody alive who is 122 years old. There's nobody alive who is 120 years old, or 119, or 118, or 117. This is the opposite of progress. This is stasis, and it's making some scientists wonder, whether humans have reached the local limit of our ability to extend life. Today's guest is Professor Olshansky from the School of Public Health at the University of Illinois at Chicago. He is the author of a new paper entitled Implausibility of Radical Life Extension in Humans in the 21st century. We talk about progress and stasis in what I

suppose you might say is the most important science project in human history. how to increase human life. I'm Derek Thompson. This is plain English. S.J. L. Shansky, welcome at the show. Yeah, thanks for having me. So in the open, I try to give listeners a sense of the sweeping history of longevity. Before the 1500s, most international records show that roughly half of children in every civilization for which we have data died before their 15th birthday.

But that since the 1800s, at least, we have... have consistently added years and years to the average human lifespan. And there's so many different people that have played a role here. Edward Jenner and the smallpox vaccines, Semmelweis telling everybody to wash their hands, John Snow in the cholera map. And I was wondering, you know, you're an expert of the history of longevity. And if I told you that almost like at the beginning of like a fantasy sports draft, you have to pick one thing, the most important.

thing that we did to extend human life since the scientific revolution, what would be that first draft pick? What would you select? Yeah, I would pick a player that had multiple skills, and those skills would be the ones that would be, you know, basically indoor living and working environments, refrigeration, removal of waste, the basic public health that evolved in the beginning of the 20th century, which was foundational to all of the major changes that occurred in the rapid. I mean, that's what caused the rapid increase in life expectancy in the early 20th century. Yeah, there were advances that happened in, you know, the mid-19th century, even the 18th century. but nothing really parallels the suite of advances that we, you know,

collectively we call public health, but it's really sort of these cushy environments that we live in. You know, here we are. I'm indoors in my home in this controlled environment. I've got a refrigerator in the other room, a bathroom over there. There's clean water that I can access. There's a lot of things that I don't have to worry about that generations today, don't have to worry about that virtually every human throughout history had to worry about. And so, yeah, the answer would be basic, basic public health in the early 20th century that really

launched this revolution in human longevity. I take two points from that answer. The first is, I don't remember where I've heard this saying the first time, but something like 95% of health happens before you get to the hospital, to a certain extent that's what you're saying, that health happens where you live and the public health achievements like indoor plumbing and refrigeration that make our home life so much healthier than it used to be might be just as, if not more important than the invention of specific medicines that help us when we do get sick, the penicillins and vaccines of the world. I mean, look, the potential for longevity has always

existed within humans. If anatomically modern humans arose 200,000 years ago, if you brought those folks into the present in our modern world, they would live as long as we do, if not longer, for reasons that you could ask me about later. But for the most part, humans are humans and all we have done is unlock the potential for longevity that was always there. Now, keep in mind, there have always been long-lived people. Even a couple thousand years ago, I believe that there were some pharaohs that made it out at least into their 90s, maybe even past 100. So the potential for long life was always there for some. We have now unlocked the opportunity to live a long life for most. And that is a really big deal for reasons that we'll be discussing later,

but it really changed the landscape of human aging and longevity and survival. And we're living it now. But the funny thing is that I wrote a paper not long ago with a colleague about communicable diseases and how in our modern world we seem to forget how valuable and effective vaccines are, eliminating these childhood diseases because we don't see them anymore. We don't see smallpox. You know, there's a, you know, even measles, mumps, rebella, we don't actually see people with this anymore. And yet, you know, some people seem to be averse to using some of these major advances in public health that have really saved our lives and allowed us all to live this long.

So it's been a remarkable ride in the last 150 years, but, yeah, this, and we'll be discussing this ride going, forward, but we've done something very unusual. You don't really see it in the wild. Most animals don't live to old age. The normal hazards that exist for most species kill them early. I mean, we were no different. And so the way in which you could see aging is in these indoor cushy environments that we've created, which now you could see our pets live long, and you could see zoo animals live long, because guess what? They've been brought into these controlled environments where the things that normally kill them have been pushed aside. I'm thinking about this idea that so much of why we live longer is because our natural

home environments have become so much safer. And to me, I think a theme underlying that principle is the distinction between invention and implementation that is not enough to invent the mechanics of refrigeration. What allows people to live longer is the fact that refrigeration technology enters 90, 95, 100% of homes in the modern world. And it reminds me of this fact that I was listening to the author Stephen Johnson's book, Extra Life, A Short History of Living Longer, which is a book about precisely this topic, the history of extending human lifespans.

And he talks about the history of pasteurization. And he points out that milk for hundreds, thousands of years was so often contaminated with bacteria and people died of tuberculosis drinking milk all the time. Once again, a communicable disease that in the rich, world people don't have to worry about when they're pouring milk into their cereal these days. But there was a 60-year gap between the invention of pasteurization in the 1860s and the widespread issue of pasteurized milk in the United States in the 1920s. And here again, you get this lesson that it wasn't enough to solve the problem of bacteria in milk with chemistry. You needed to

solve the problem with a social movement, with public health policies to push the science of pasteurization into the law. Do you think, do you also see in your public health work this, this important distinction or interplay between invention on the one hand, making a technology possible, and implementation, on the other hand, making the invention widespread? Yeah, I mean, look, I'm from Chicago. I went to school at the University of Chicago. down on the south side. There's a famous street that runs from Lake Michigan right down the side of the University of Chicago.

So as you're moving away from the lake, universities on the right side, and there's poverty on the left side of the street. The life expectancy on the right side is, you know, somewhere in the 80s. The life expectancy on the left side is somewhere in the 60s or 70s. So you can have these differences that exist. across the street from each other at the same time. And that's, you know, these are called disparities that in, in public health. And they've been around for a long time.

These disparities have always existed, probably always will exist. It's the differences between the rich and the poor. But you're right. I mean, in the modern era, we've gotten much better at disseminating basic public health to everyone. Now, here in the United States, we don't even have universal health care. the people on the left side of the midway layasants are not, you know, going to see a doctor like the folks on the right side. They don't have access to the, you know, to clean indoor living

environments, for example. Their access to food is totally different. You have one side that's extremely obese and another one that isn't quite that obese, but still obese. So, yeah, you're talking about the social determinants of health and those are profoundly influential in influencing survival going forward. And it's in our world today. Yeah, I can talk to you about invention, implementation as history for an hour, but we're here to talk about the future,

and I want to move to the future right now. So radical life expectancy. If you take the historical trend between the 1840s and the late 20th century, life expectancy in rich countries increased at a pace of about 2.5 years per decade. And if you take that trend and you extend it into the future, and if current progress and life expectancy continues, most children born in the 21st century will celebrate their 100th birthday.

What do you make of that extrapolation that I just implied? What do you make of this prediction that some demographers put stock in that most children born in this century will celebrate their 100th birthday. I think it was a fundamental mistake in thinking when this concept was presented. And the reason why is actually incredibly simple and easy for folks to understand. The radical life extension that occurred in the 20th century, and it did occur, it was about three years in life expectancy added per decade, beginning in 1900, going all the way to 2000, it was quite remarkable, but the vast majority of that increase in life expectancy was the result of the first longevity revolution, which saved children. So that's the first

thing that you mentioned. You can only do that once. Once you've saved the children and you've pushed out survival, you know, well beyond, you know, five, six, even seven decades of life, then the game that you're playing is a different one, which is the game that we're playing today. So the longevity game in the early 20th century, which led to accelerated increases in life expectancy, was amazing. It's what basic public health did for us. We manufactured, you know, decades of life by saving the young. But you can't manufacture the same number of decades of life for older individuals. Something gets in the way.

It would be called aging. the basic biological process of aging, the changes that occur in cells, tissues, organs, and organ systems that lead to what we call aging. Look, I'm 70 years old. There's a difference between you and I, which should be visible if somebody were to look at pictures of us. And that's what aging is. It's these fundamental changes that occur in our body with time.

That's currently immutable. It doesn't mean that it will be in the future, but currently it's immutable. So what's happened is that we've exposed the people that ordinarily would have died at younger ages to a biological process of aging that is currently immutable, which is the reason why we have said you cannot experience a gain in life expectancy today like the one that was observed in the 20th century because the longevity game is a different one. Now we're dealing with older individuals. previously we were dealing with younger individuals. I have some skeptical questions about this thesis that I'm going to touch on in just a second, but I first want you to give the strongest possible proof of this idea

that radical life extension and humans in the 21st century is less plausible than some of the techno-optimists want to make it seem. You just published this paper that's gotten a lot of attention, the New York Times, the Wall Street Journal. Let's go inside this paper. what data did you find that most convinces you of the fact that we right now are near the peak of maximal human life expectancy in the rich developed world? All right. I'm going to take you back in time a little bit because this is a good question

and I can tell you that the light bulb turned on for me in 1989. I mean, I actually know exactly when I discovered in my own head why this has to be. It was based on a set of calculations that my colleague and I did trying to figure out how long humans are capable of living. Now, we actually asked a very straightforward question, but we tried to answer it in a different way. I'm going back to 1989 and an article that we published in science in 1990 entitled In Search of Methuselah, Estimating the upper limits to human longevity. And it was when we were working on that paper that we tried to reverse engineer the answer to this question, how long can humans live? And what we discovered in answering this question, and it was a fairly straightforward analysis, we said,

how low would death rates have to go in order to raise life expectancy up to some higher number relative to where we are today? And what we saw really shook us to our core. I mean, I hadn't really done that calculation before, but what we discovered was that the longer we live, the more difficult it is to raise life expectancy further because the magnitude of the reduction and the death rates required to get there rises extremely rapidly at older ages. Keep in mind, saving the life of a 70 or 80-year-old is not the same as saving the life of an infant. When you save the life of an infant, you add decades to life. When you save the life of a 70, 80, 90, or 100-year-old through whatever technology that you're using or manufacturing, you only add small, incremental amounts of survival time.

So we speculated back in 1990 that life expectancy must slow down. not that it should slow down or that it's likely to slow down, but that it has to slow down. And that the reason why it has to slow down is because enough of the population is now surviving past the age of 80, that they are exposed to this currently immutable force of biological aging, which we can't currently manipulate. And so once, I mean, ultimately, it's what led to this limited lifespan hypothesis that we set forth in 1990. We basically said, we don't think life expectancy for humans can go much above 85 for a national population, about 88 for women, about 82 for men. Now, it was a hypothesis. We really didn't know for sure what that number was, but my goodness, all the evidence was pointing in that direction.

there were a lot of people that came out with articles right after ours saying, no, no, no, advances in medical technology will accelerate and it's going to drag life expectancy with it. By the way, you hear the exact same thing today. And we said, well, the first is going to happen, but the second can't happen unless those advances in medical technology alter aging itself. Now, this concept did not sink in for most people. They held on to this belief that if you continue to exercise, you continue to eat right, we continue to find ways to cure diseases that it will continue to push up survival and make us live to 100. And we're going, no, it can't.

As long as aging gets in the way, these cures for major diseases aren't going to have nearly the impact that you think. And we showed that in our 1990 article in science, where we said, look, if you cure cancer, you only gain about three years in life expectancy. If you cure cardiovascular disease, you only get about four to four and a half years in life expectancy. So the question arises, well, if we cure everything, how come we're not immortal? And the answer is because aging gets in the way. The underlying biological process of aging marches on. So guess what? We waited three decades. That was 1990. You know, a couple of years ago, we actually started. this manuscript three years ago, but we've been tracking the data and we knew exactly where

things were going, and we said, all right, it's time to let the world know what actually happened. So we went and did this analysis. We looked back in time over the last three decades, and exactly as we had predicted in 1990, even though there were significant advances in the developments of life-extending technologies, we could show you the one, three, five, ten-year survival rates for people with all these major diseases, associated with all these new technologies that have been developed, the rate of improvement in life expectancy went down, and not by a small amount. And it never reached this three-year per decade anticipated increase that these proponents of radical life extension had proposed. Now, there were a

couple of other things. You know, you were asking for definitive evidence. There were a couple of other things that we show in the manuscript, which I haven't talked a lot about during interviews, but my goodness, it's extraordinarily powerful. One was an answer to a simple question, how much would death rates have to decline to increase life expectancy by one year? Just really simple, right? And so back in 1990, we demonstrated that it takes about a nine and a half percent reduction in death rates from all causes at all ages to go up one year. That's it. But in today's world, it's closer to somewhere, depending on where you are, 10 to 12%. So in other words, it is far more difficult today to add one year of life expectancy than it was 30 years ago.

Thank you for that really comprehensive answer. I want to try to summarize it for myself. and I want you to quickly tell me if my summary is right before we move on to some other really interesting questions that I have for you. Our progress extending human life, on average, is slowing down. And one way to see why it's slowing down is that in the 19th and certainly the 20th century, we sort of picked the low-hanging fruit of extending human lifespans. And that low-hanging fruit, to a certain extent, was we found a way to build a kind of castle around the body to protect us from more communicable diseases, viruses and bacteria.

And we did this by inventing things like vaccines and by distributing and implementing things like vaccines. But now that we've solved those problems, we face a very different kind of problem. We need to build a different kind of defense system to protect us from the processes of aging that originate not from outside the body, but from inside the body, which means that they seem more intrinsic to and inherent to our species. And all species, it seems, have certain average lifespans that they can't naturally exceed. And we seem to have one too. And so someone listening to your answer might think, well, you know, what about GLP1 drugs? They seem quite astounding, and I think they are. Or what about CART cell therapy, which I'm very interested in in terms

of its possible effects on curing cancer? I imagine you might say, well, look, these technologies might make an enormous difference in individual lives. They might save individual lives, but they won't make a large difference in average lifespans because the problem with extending average lifespans now is a problem of fixing aging, which is intrinsic to humanity and not a problem of fixing communicable diseases, which are extrinsic to our species. Yeah. So that's a good summary, and let me amplify that. The latter part of the 20th century has been marked by pretty dramatic advances in medicine that have manufactured survival time for us. In fact, I would argue that the vast majority of all humans alive beyond the age of 60 are living on manufactured time, time that was created for us, not just by public health, but by medical interventions, pharmaceuticals, for example, which work. They are enormously successful. I mean, you know, statins work. They lower the risk

of cardiovascular disease. Stents work. They produce survival time for individuals who ordinarily would die from cardiovascular disease. Chemotherapy and radiation work in treating the consequences of cancer. All you have to do is look at the survival rates, and the survival rates tell you a very compelling story that we have been extraordinarily effective in manufacturing survival time. But what this does is it reveals something foundational, which I think perhaps maybe also it provides an additional explanation for why there's a limit to human longevity. We have argued that if you pull away all medicine entirely, you can sort of keep public health going, right? But you pull away all medical technology, everything. We actually think that the

natural limit for human longevity would be closer to age 60, maybe lower. And, you know, we refer to that as sort of the natural, the natural limit to longevity. So we're actually suggesting that the, the true limit to human longevity is behind us, not ahead of us. There's a conventional view among many that we can just continue to manufacture time through medical technology, and all we're doing is revealing the opportunity for this body to live this long. No, I mean, we can do that. Of course, I think we can continue to manufacture time. It's just that we're going to get less and less of it as long as these interventions only influence diseases. And you summarized it very well. There's no question that some of these new advances in technology are going to allow us to

deal with cancer much more effectively than we do today. Cancer, you know, people, I can't remember the exact percentage, but it's somewhere just over 20% of the population actually dies from cancer. So remember, if you cure cancer at the population level, it doesn't have nearly the effect that you might think on the metric of life expectancy. Death is a zero-sum game. So if you cure cancer, you reduce it down to zero, all those people will eventually die, which means something else has to go up. So the question is, what are you trading for? It's a game of whackamol. That's the way I've described this recently. And the game of, you know, the whackamol game that we've entered into now is such that we're living long enough that if each mole represents a disease, there's a lot more of them. It's

called competing risks in epidemiology. And there's a lot more of them. And they're coming up a lot faster the older we get. So when you push out the envelope of survival, the game of whackamol gets increasingly more difficult to win. And in the end, it's not a winnable game. You're just trying to keep up with the diseases that are accumulating in these bodies. But I, you know, I like the way in which you describe this, but you have to realize that once the light bulb turns on and you actually see that the slowdown is not a product of failure, it's a product of success. It's a thought product of all of these major advances that have occurred not just in public health, but in medicine, which have manufactured survival time for us very effectively.

But we've argued they're running out of steam, in part because we are butting up against something that is very difficult at this moment anyway to get around. So that's the reason why we use the phrase, life expectancy must slow down. Not that it is likely to, but it has to slow down. Right. Yeah, which is why I somewhat like the optimistic frame that the fact that this fruit is hard to pick is proof of the fact that we've picked the low-hanging fruit.

It's a little bit like if I was having a conversation, not with a longevity expert, but with a physics expert. And I said, why is it so hard to unify quantum mechanics and Newtonian physics? It's like, well, it's actually very difficult to come up with a theory of, of every phenomenon in the universe that works, that's much harder than explaining

how celestial bodies move in space or how electrons move inside of a cell or inside of an atom. It's just much harder. And so this goes to a theme, I think, that exists throughout technology and throughout science, that progress can become harder in a field, not because we're getting dumber,

but rather because we have been so smart as to solve a bunch of very, very difficult problems, which by definition leaves the hardest problems unsolved. But that leads me right into my next question for you, sir. I think you'd agree that the modern world has somewhat evolved from people largely dying young due to communicable diseases, diseases outside of the body, to more people dying old of degenerative diseases that originate inside the body. Why are degenerative diseases harder to cure than communicable diseases? Why is it, why would it naturally be the case that the diseases of, say, aging would be more mysterious

than, say, smallpox, which we sort of fixed up in the 1790s? So I published an article on this topic several years ago in an Israeli medical journal where I tried to tackle this very question. And I used Darwin and Michelangelo as a... sort of images of how to address this question. Now, Darwin, of course, argued that evolution occurs because of flaws that exist in the way in which these bodies operate, basically. Michelangelo painted humanity as this sort of perfect being. trying to approach perfection.

And I would say that both elements of that story are correct in their own way. So we have these nearly perfect, absolutely amazing maintenance and repair mechanisms for dealing with the accumulated damage to the DNA that occurs in our cells on a daily basis. You know, when we breathe, when we eat, when we metabolize, we're producing toxins. within our own body. You know, when you think about it, you sort of wonder how we actually live as long as we do. But the fact is that humans evolved this amazing set of maintenance and repair mechanisms that, you know, address, I think the estimate has been something like 10,000 hits per day per cell,

which could do damage and do damage. And these are repaired on a daily basis with a high degree of efficiency. but it's not perfect. And it's that lack of perfection that leads to the accumulated damage to cells, tissues, organs, and organ systems that ultimately leads to the changes in our body with the passage of time that we could see between you and I, you know, visually, but inside our bodies as well. So organs operate with less efficiency. Even on people that live these perfect lifestyles, you know, they exercise, they eat, right, they're still going to get a stiffening of their cardiovascular system.

We will lose muscle mass. We will lose neurons with the passage of time. These are non-replicating parts of the body. And once they're lost, they're gone forever. These knees and hips, these hinges that we have in our bodies, weren't meant for long-term use. So we use them a whole lot longer than what I would refer to as their biological warranty period.

Years ago, I tried to explain this in an article in scientific, American entitled if humans were built to last, where we basically showed you what the body might look like if it was designed for long-term use. I had to say, I saw this in my research for this episode, and we'll put this in the show notes. There are pictures of what the optimal human body would look like if we were designed not to reproduce and then basically evolution stops caring about us once we leave our reproduction age, but rather what if evolution most cared about us living from, say, 65 to 95? And essentially, the human being kind of looks like a forward-slumping kangaroo. It's like our knees bend in the opposite way. Our backs are angled forward, I suppose,

to relieve the pressure on our necks. Our eyes are designs that our retinas are less likely detach, our prostrates live outside the urethra. There's a bunch of very, sometimes funny, sometimes somewhat gruesome edits. Before we go to, I really want to ask you about the future of biological aging, but maybe just tell me, if you recall, your favorite design tweak to the human body if evolution designed us optimally to survive

from starting at age 65. Well, so the funny thing is, is that none of those tweets would work in the real world. And a lot of people took us literally when we wrote that article. And, you know, when my colleague, Bruce Carnes and I started working on it, he actually wanted to take on God in the article basically saying, well, God's a bad designer because these bodies don't work nearly as well as they should. I said, yeah, we're not taking on God in Scientific American. That's just not going to happen. And so actually, as it turns out, virtually all of those tweaks that put in there were fanciful. None of them would actually work in the real world. Actually, if you

reverse the knee joint, which was my idea, by the way, and you tilt the upper torso forward about 15 or 20 degrees, which is what we showed in the real world, that animal would just fall over. It wouldn't actually work. So the message there was not that we can design any better, but that we have to live with the design that we have. And the design that we have is flawed. It wasn't really meant for long-term use. That's why we, you know, when we get older, we get new knees and hips and shoulders and elbows and, you know, why we have to do all these things to try to protect our brain. It's just a recognition that these bodies weren't designed for long-term use. We were looking for an alternative way of communicating the same message that we discovered in 1990, which is there

has to be a limit. We know what it is. It's influenced by body design for sure, but it's also the things that go on inside the body. And we don't have time to discuss it now, but we actually just wrote another article on the same topic on how to manipulate the things that go wrong inside the body to solve these problems as well. So it was really, we were always looking for ways, effective ways of communicating these complicated concepts. And it all culminated in this latest nature aging paper, which I think provided pretty

powerful evidence that the very thing that we speculated on in 1990 actually has happened. Well, Professor, I'd actually like to take you up on that offer and travel inside the body because there are several points in this recent paper where you say that while we should be humble about further increases and life expectancy, that humility is contingent on the processes of biological aging, which might be in some distant technological future slowed down. What did you mean by this? What did you mean that we should be humble about further increases in life expectancy unless the processes of biological aging can be markedly slowed? So this is a good question. So first of all, humble probably wouldn't be the word I would use.

I would say grateful. We need to be grateful of the fact that medicine and public health gave us these long lives, we wouldn't be here without it. Most of us wouldn't be here. And so we need to be grateful for what's been given to us by medicine and public health. But as we indicated in the paper, all of that has to slow down and it has to come to an end unless we do something different. Now, therein lies the interesting element to the end of the manuscript, which is a very optimistic message, basically saying, look, while these band-aids that we've created, these medical band-aids are yielding smaller and smaller incremental amounts of survival time, there's, the doors wide open for us to alter that immutable force that I told you. It's always been lurking

in the background. There's no, you know, a set of genes that we have that force us to age. There's no time bomb that goes off that says you can't live beyond X number of years. So aging is inherently modifiable, and scientists in the field have now demonstrated that it can be manipulated. And in fact, it has already been manipulated in other species in the first clinical trials, testing some potential therapeutic interventions to slow aging, have already started. So there's an exciting new public health movement in front of us that is at least as exciting as the one that we were talking about, you know, the first draft pick for extending healthy life. Well, this would be the first draft pick today, which would be Gerald, which is this effort to slow aging. I think this is really an exciting time because scientists are on the verge, I think, of a breakthrough that has the potential to influence.

the health and quality of life of most people alive today. Now, can I tell you in advance that it's going to make us live longer? No, I can't. Nor can anyone else. Is it likely to make us live longer? Well, if you live healthier, younger and middle ages, chances are you're going to live healthier and longer in older ages, the problem is quantifying it. When somebody comes along and says, oh yeah, you know, drink this elixir, take this pill, it's going to add 50 years to your life, that is an untestable scientific hypothesis. We actually use that language in the manuscript for a very specific reason, because people are making those exact claims today, that interventions, A, B, and C, whatever it is that they're

working on are going to make us all live to 100, 120, 150. You can't make those claims. Those are unverifiable claims that are being made. But what you can... Correct me if I'm wrong. You can make those claims. You just have to wait 50 years to know. if they're true, right?

That's true. If I start taking a pill right now that says, you know, you take this pill that allow you to live to 130, that bill doesn't come due for another math is a little short here, you know, 82 years. So I can take it for 81 years and think that it's doing a good job. Anyway, you are, you are... Well, wait. The people that are selling those are hoping exactly that, that they think that it might

work in the future so they're taking it today. I mean, that's the basis for some of this work that's going on on freezing people's bodies and heads. You know, there's no evidence that it actually works. No one has ever been revived from having been frozen. And so, you know, what are they banking on? They're banking on something in the future that will allow people that have these frozen heads or bodies to be revived. So it's all based on something that doesn't exist and has never been proven. Yeah, right. Either we're doing something. They're banking on the operative. And they're banking on the opportunity cost of freezing their bodies or their skulls being zero. Because, you know, heads, I live forever, tails, I'm dead anyway.

So what exactly is the cost? I would love to close in the exact same way that we opened. And you introduce the possibility of being able to close this way, and I like it. The same way that I asked you for a number one draft pick for the most important intervention that has extended human life in the past. I love you to name your number one draft pick for the most likely technology within this field of biological aging to most likely to succeed in the next generation. So people listening might have heard of, you know, some pills that are being taken or medicines that's been given to slightly extend the life of rats like metformin or rapamycin. In Silicon Valley, they're working on what they call cellular programming to take some of the principles. of engineering and to apply it to cellular senescence, to stop the process of aging at the

level of the cell. We talked a few weeks ago on this show with folks from DeepMind that are trying to use AI to master the science of proteins and proteomics so that we can both allow ourselves to make optimal proteins and introduce external proteins to our bodies that might allow us to live longer. That's just a very partial menu. The field is wide open and the choice is yours. Number one draft pick for most likely technology to extend human lifespans in the field of biological aging.

It is? Well, is it okay if I give you a longer answer than just a word? Oh, no. It can be as long as you want. Yeah. I would just like the answer to be relatively singular, even if the answer is longer. I will give you an answer, recognizing that there's a decent chance that's going to be wrong. But this would be one of those circumstances where I would love, I don't care if I'm right or wrong.

Right or wrong doesn't matter here. The fact is, is that the bench to choose from is huge. You've got a stadium full of options to choose from. And that's what's so exciting about the field of geroscience is that there's so many pathways. And this is where science is extraordinarily exciting. You have so many scientists zeroing in on this in one way or another, and there's a lot of money flowing into this. This is all healthy, in my view, that we should be pursuing more than one means of going after aging. And I, you know, while I don't have an answer and whatever answer I would give you, you know, chances are given the number of opportunities, the number of draft choices that are available for number one is extraordinarily large. I actually do have one thing that I do look at the most. You know, there's lots of things that researchers are looking at in shorter lived animals. You know, that's where some of the clinical trials are.

or the trials are going on, what I look at are the studies that are done currently on exceptionally long-lived people today, not other animals, but humans. And you have to realize this concept of slower aging is not only not new, it's right here in our face, right in front of us today. There are people today that are out past 100, 110, many of whom can be held. healthy. You know, their brains may be operating at an exceptionally high level. So slower aging, where biological time ticks at a slower rate, is here already in front of us right now. Studying the genetics of these exceptionally long-lived individuals who are probably experiencing slower biological time to me is some of the most exciting work. And right now, my gaze is

on those research projects, recognizing that, you know, that may not pan out. Some of these others might pan out. And they all, in my view, should be pursued. So I like them all. They all bring something unique to the equation. And I'm very excited about them also. I guess my first draft pick would be something associated with the genetics of exceptionally long-lived individuals where we can already see the consequences of success. Yeah. That's something that would love to learn about because it seems so reasonable. It seems like a bit of a lighter lift. I mean, I am incredibly hopeful that folks in Palo Alto find a way to engineer cells like their computer code. That sounds lovely. It also seems really, really hard because biology is so unbelievably complex.

On the other hand, if you have a G-WA study of a bunch of centarians or super centarians or almost centarians, folks who are living until their 90s or even a group of people that you identify as living relatively long, I think I'm Jewish related to German Jews. I think maybe there's some evidence that some Ashkenazi Jews seem to live relatively long lives. If you can find some way to sequence a lot of genomes there and isolate some areas that might be related to long life, that seems maybe like a lower lift in terms of teaching us, you know, what is this recipe for living into one's 90s and who seems to have that recipe inscribed in their DNA?

Yeah, here's the analogy, right? You have all of these options to pick. The difference between what I'm suggesting and what else is available today is that the one that I chose, I can actually watch them dunk the basketball right now. one else is on the bench. And so here I can already see success because it's already in front of me. The potential for all these others to dunk the basketball is there, perhaps even a lot easier than the ones that are dunking it today.

But this is the one I can see right now. Yeah, you know, is that going to be the one I don't know? And I'm hoping actually that there's more than one way to tackle this process of aging. I do like this question because it really, I think hones in on how we should be thinking about how to deal with these issues going forward. And I can tell you, part of the problem that we face is that the folks on the bench are some of them are basically saying, oh, yeah, yeah, I watch that guy dunking. Hey, I can dunk a basketball from right here going, yeah, prove it.

That's the problem is proving it. You actually have to prove that you can do what you say you can do. When somebody says you're going to live another 100 years longer, yeah, well, you better. You may want to rethink that particular line of reasoning because it's an untestable hypothesis. Let's go after what we can go after and measure what we can, which is why I've argued for a long time now that health span should be the primary metric of success, not lifespan. I love it. S.J. L. Shansky, thank you very much. I appreciate it.

Yep. Thanks for having me. Thank you for listening. Today's episode was produced by Devin Beraldi, our summer schedule for plain English for the next few weeks. We'll be one episode a week on Fridays. We'll see you next week.