Steven Austad
Description: Steven Austad is a Distinguished Professor and the Protective Life Endowed Chair in Healthy Aging Research at the University of Alabama at Birmingham and Scientific Director of the American Federation for Aging Research. His work uses a comparative approach, studying a wide variety of animal species to understand the fundamental mechanisms that control the speed of aging. In this episode, we hear about his incredible journey from Hollywood lion trainer to leading aging researcher. We discuss why island opossums age slower, the paradox of why women live longer but are often less healthy in old age, and what the exceptional longevity of birds can teach us about our own healthspan. Steve also offers a powerful critique of how current aging research is conducted in sterile lab environments and explains his famous bet that someone alive today will reach 150 years old.
Websites:
Publications:
Genetic Analysis of Aging: Role of Oxidative Damage and Environmental Stresses
Articles:
Ditch Dubious Anti-Aging Hacks
Mentions:
Other Podcasts:
Peter Attia’s The Drive - #333: Longevity Roundtable (2025)
Peter Attia’s The Drive - #171: Landscape of Longevity Science (2021)
Steven Austad back as a big cat trainer.
Show Notes:
[00:00] Introduction to Professor Steve Austad
[03:28] Adventures in Lion Training
[06:23] Transitioning from Animal Training to Academia
[09:35] Understanding Aging: The Basics
[12:32] The Metrics of Aging
[15:20] Environmental Influences on Aging
[19:36] Gender Differences in Aging
[24:25] Tissue Aging and Longevity
[28:39] Size and Aging Dynamics
[34:17] Hormesis and Stress in Longevity
[34:20] The Science of Hormesis and Longevity
[41:31] Cognitive Stress and Its Impact on Aging
[44:21] Challenges in Aging Research
[54:16] Exploring New Animal Models for Longevity
[58:29] The Future of Aging: Predictions and Possibilities
Unedited AI Generated Transcript:
Brent Valentine (00:00)
Welcome back to Discovering Academia. We are two college students who travel the world talking with academics about their research, passions, and current events. Today we talk with Steven Austad a distinguished professor of biology at the University of Alabama at Birmingham.
Keller Kramer (00:14)
Professor Austad's work explores the comparative biology and evolutionary mechanics of aging. In this episode, we discuss how we went from training lions for Hollywood movies to researching the evolutionary reasons for aging. We dive into why women consistently outlive men, the critical flaws in how we currently study longevity in labs, and why he bet over 100 million that someone alive today will live to be 150. We hope you enjoy.
Brent Valentine (00:37)
Welcome Professor Steve Austad. Thank you for coming out today.
Steven Austad (00:40)
I pleasure to be here.
Keller Kramer (00:42)
We'd love to start off by hearing, what is it like to ride a lion?
Steven Austad (00:46)
it's a very unusual experience. Lions, if you've ever seen them walk, ⁓ they actually roll their shoulders quite a bit. So I didn't have any trouble riding a lion. could just grab basically the fur in the back of their neck and ride it. But I had a girlfriend when I was training lions who was an expert horse rider, and I had her try it. And she immediately fell off.
because she wasn't used to the way the shoulders were rolling, so she went right up. So yeah, it's fun, but I wouldn't advise trying it with any lion. It has to be the right lion.
Brent Valentine (01:28)
We'd love to hear a little bit more about your background working with lions and just like animal keeping as a whole and kind of how that led you into academia.
Steven Austad (01:36)
Yeah, so ⁓ I just stumbled into this job. A friend of mine had a couple of African lions for pets because he was crazy and he got an offer to use them in a movie and he needed somebody to help him transport them. I was living in Portland, Oregon at the time and I assumed he had a horse trailer or something like that that was modified for lions. I said, sure, I'll take a long weekend. We'll drive down to LA.
When I got out to his place, he said, ⁓ Steve, could you help me take the back seat out of the car here? And we put a lion in the back seat of the car and took off for Los Angeles. Nothing between the front seat and the back seat. So that was my introduction to lions. Later on, know, months later, when I knew more about lions, I thought to myself, he had to be out of his mind to even think about doing that. I mean,
Keller Kramer (02:32)
You
Steven Austad (02:34)
You know, we were fortunate that that would nothing really bad happened on that. The worst thing that happened was, ⁓ it scared the heck out of me. So when he was driving, the way he controlled the line, had an electronic cattle prod. And if you've ever seen one of these, you push the button and it buzzes, you know, it'll shock the cattle. And so what he said is if sure. So gets up and starts walking around in the back there, which made the car tip back and forth. He says just.
put the prod in front of his nose and push the button. He's afraid of it. So I tried that and it worked a couple of times and then we ran out of battery in the prod. So I said, what do we do now? And he said, well, just put it, stick it up front as those would go bzzzz with your mouth like that.
And I thought, lions really that stupid? And it turns out they're not, you know, that didn't work at all. And by this time, I suddenly noticed that he was scared and I didn't know enough to be afraid, but I thought, well, if he's afraid, then I should probably be afraid too. So I actually had to make an emergency and pull off on a logging road. It's middle of the night by now, get the lion out of the car.
and walk it. And he walked it on a leash. And I drove the car behind him to provide some light. then every time, but every time, this was a logging road, the middle of the forest in Northern California, every time the road would bend and he'd lose sight of the car, when I came around the corner, the lion would attack the car, would jump on it and hit the windshield and all. Eventually we tired the lion out and got back in the car and...
Brent Valentine (04:18)
You
Steven Austad (04:24)
The rest of the trip was relatively ⁓ uneventful except when the police pulled us over at about 3 a.m. But when we got to LA, the movie producer who wanted to use his lion offered me this job, my shock and surprise. And I said, now you don't understand. This is the first time I've actually ever been around a lion. And it was pretty scary. And so I don't really think so. guess, don't worry about it.
I've hired a number of professional trainers and you can just learn from them. So ⁓ it sounded exciting. It also turned out that he was ⁓ married to an actress that I had a crush on since I was about 10 years old. And ⁓ when I found that out, ⁓ I thought, my goodness, I get to meet her. It turns out I lived at the house with him, his wife and their daughter, who's also
an actress named Melanie Griffith now. And so ⁓ that's how I got into it. And then I did it for about three, three and a half years. I got out of it not long. I got pretty badly injured one time with, ⁓ you know, I made a mistake and you find out your mistakes quickly when you make a mistake with the lion. So I had a few weeks in the hospital to kind of contemplate my future.
And I developed a real interest in what makes animals tick. And so I thought, well, my future probably isn't in lion training. Otherwise I can be a very lengthy future. ⁓ So what could I do? I thought, well, what about going to graduate school and studying animals in a more rigorous fashion? ⁓ I started, while I still doing this, I started going back to school. had a degree in English literature at the time.
and just taking science classes to see if I really liked it. And I did. By the time I went to graduate school, I wanted to study lion behavior in the wild. That was my goal. And I went over to East Africa to try to get involved in this famous Serengeti lion project. ⁓ But that didn't work out for one reason or another. But I went on and did my PhD in something unrelated.
still not related at all to aging or longevity. That interest came about when I was a postdoc and I was working in the field in ⁓ South America. And I discovered quite by accident that opossums, very similar to the opossums that you have there in California, lived only about as long as a mouse. They lived only a year and a half, maybe two years at the outside. And I was shocked.
Keller Kramer (07:01)
yeah.
Steven Austad (07:20)
At that, you know, we all have kind of have an idea, I think about how long things live. And I thought, was about the size of a house cat probably lives, you know, 10, 15 years like a house cat, but no, you know, they get old. mean, they don't just. They don't just die when they're young. They get old when they're young. about 15 months of age, they look fine. Of 18 months of age, they'll have maybe have cataracts. I may have lost a lot of muscle mass, been parasitized.
all kinds of things that they really undergo this accelerated aging. And I was so interested in discovering that, that it sort of took over my life. Why does this thing age so much quicker than a house cat? And are there things that are about the same size that don't age as fast as a house cat? And why is that? those were basically the questions that drove me into aging research. had nothing to do with the...
biomedical aspects of it. That came much later.
Keller Kramer (08:26)
And how do you think your unconventional, I guess, introduction to academia has informed the way that you approach creating research problems and conducting those research?
Steven Austad (08:36)
Yeah, that's a really good question because I do think it's had an enormous impact. And I think the main thing is that I've spent a lot of time around animals, both captive animals, because I didn't just do lions when I was training animals. I did some other animals, elephant, know, bears. But also I spent, you know, 20 years as a field biologist. So I was around animals in the field all the time then. And I think what it did is it gave me
an appreciation for the impact of the environment on animals that I don't think most biomedical researchers have. You know, I think they think of animals while they must have evolved in these little cages and, and, you know, they don't have very much respect, I would say, for the animals sensing of the environment. And I do. And I guess the thing that that's done is it's led me to ask sort of different questions.
I guess than most of my colleagues would. And to also question their own research in ways that they would never do. I don't do it to try to embarrass them. try to figure out something. And so it's served me well, I think.
Brent Valentine (09:56)
Yeah. Before we get into those questions, I to dive a little bit more into like, what is aging and why do we age?
Steven Austad (10:05)
Yeah, so the evolutionary answer to that, which is really what my original question was all about, is that basically ⁓ we age because we eat and breathe. Basically, I mean, the basic processes of life are destructive. Metabolism is destructive. And evolution has created lots of ways to try to mitigate the destructive aspects of living. ⁓
but it hasn't perfected those. And ⁓ what really causes us to age is the fact that ultimately we cannot combat the destructive processes of life with total efficiency. And some animals are good at, very good at it. We're very good. You we're the longest live terrestrial mammal. So.
We're very good at combating those things, but there are things that are better. And I'm really interested in those things that are better and what we can learn from them. If you think about it, the fundamental way we go about studying aging and laboratory animals is we take animals that are demonstrably unsuccessful at aging. They age quickly, they fall apart in a hurry.
And we assume if we can discover ways to make them age a little bit less rapidly, that that will translate into something that will make humans who are already quite successful at resisting aging, ⁓ age less rapidly as well. And we may do so, but I think an alternative approach ⁓ is to look at animals that already do things better than we do and try to figure out how they do it. know, the underlying messages
Evolution is smarter than we are, and it's had billions of years, billions of species to experiment, and it will have come up with some solutions that we probably wouldn't think of.
Keller Kramer (12:12)
And when we say aging, what are some of the metrics that are, guess, commonly agreed on to define, you know, when a animal or a person is aging? Before the podcast, we talked a little bit about oxidative stress and dealing with shortening. Are those the main ones? Are there other ones that are commonplace?
Steven Austad (12:32)
Well, I think those are those are what underneath what's underneath the hood. But I mean, what we observe, I think, is a decline in function, a loss of ⁓ muscle strength, the loss of speed of cognitive processing, a decline in the effectiveness of our immune system. All of those things underline all of those things that are complicated. I like to say.
Because some people think that aging and disease are the same thing. That aging is just the accumulation of diseases. And I think that's absolutely wrong. And the reason I say that is that you can take the healthiest 50 or 60 year old in the world and that person cannot run as fast as they could when they were 20. And I don't care how much they train. That's just something has gone on. They can be healthy. They can be highly trained.
but there's this gradual decline in function that we don't know how to do anything about it. That to me is aging. Now what underlies it, what makes that happen, I think is complicated. If it were simple, we would have sorted it all out by now. But we do have some quite, I would guess, robust successes.
at least making our short-live, rapidly aging animals do better. What we don't know is whether those things are going to translate to people or not.
Brent Valentine (14:06)
Yeah. And then when you're talking about humans being like very good agers, is that modern day humans or even more like remote tribes or someone who's like in a more like naturalistic environment, they also classify as good agers.
Steven Austad (14:21)
Yeah
Yeah, so the rate at which we age and the way we age has really been produced over really thousands of years of evolution. And so we haven't had that much modern life yet. So I think it's largely was the speedometer was or the odometer was set thousands and thousands of years ago. because it takes evolution that a long time to work.
I think that it was, we have to think of things as how they were. Now, one of the first studies I did in aging was a field study to test this idea. And what I did then, I was still working on opossums, but I was working now on North American opossums. I compared the aging rate of animals on an island compared to the same species on the adjacent mainland.
And the reason I did that is that the island didn't have any predators and it had been around for 5,000 years and no predators. And I thought, well, that ought to be, and, and opossums get killed, you know, even before there were cars around, opossums got killed by predators, about 80 % of opossums get killed by predators. So I thought, well, if there are no predators and there's a history, thought, you know, 5,000 year history of no predators, then evolution.
should have slowed aging in those animals. Because if they weren't likely to get killed by a predator, then it became advantageous to, let's say, build a longer lasting immune system or eyes that don't get cataract so fast and all the advantages to longer life. And so I spent a few years doing that project and I found it was true. The animals on the island ⁓ aged more slowly. They didn't just live longer because you did
expect they would live longer if there's no predators, right? But they age more slowly. If you looked at the way that they aged in terms of reproduction, I also had a way of looking at their aging and their tendons, and their tendons age more slowly. ⁓ So they clearly, you know, that clearly fit with the whole idea. But the next question, because science is always about the next question, you know, you get a
an answer to one thing and it raises a dozen different questions. Next thing I wanted to know was how do they do it? What's gone on in such a relatively short time to make them age more slowly? But at that time, that was in the early 1990s, we didn't really have the genetic tools to examine that. ⁓ And so I was kind of stuck.
I wanted to transfer some opossums from the island to the mainland to see if it was just an environmental effect or all. I didn't get funding for that. Years later, actually when I was doing a television show, BBC show, it actually flew me back to the island to do some shooting. And I thought, well, maybe by now the genetics had really developed, molecular genetics had really developed. Now I thought we could really do something with this.
Keller Kramer (17:37)
Thank
Steven Austad (17:42)
Unfortunately, in the interim, had happened, one of the reasons I chose the island was that there were no bridges between the island and the mainland. And opossums aren't very good swimmers. So I thought, this is really an isolated population. When I got back to the island, though, a bunch of animals that hadn't been on the island before, like raccoons, armadillos, now were on the island. So I thought, there's been some sort of introduction here.
probably my nice little isolated gene pool there is no longer there. So I went on it. So I tried a different tack. thought, you know, we have really well-developed ⁓ genomics, molecular genetics of mice from having used them in the lab. And in last 500 years since European mariners went all over the world, they introduced mice to all the islands of the world.
So just thought I could replicate this maybe, and at the same time get the NIH to pay for me to go to some tropical islands and spend some quality time scuba diving. So I did that. I collected mice from a bunch of islands. We brought them back. We ⁓ basically looked at how long they lived in the lab, a whole bunch of things. Unfortunately, that
project didn't pan out the way we wanted. One of the islands, actually, the mice from it did have ⁓ a reproductive lifetime that was longer than any mice that have ever been studied before. ⁓ But I think the problem I had is I took the easy way to do this study, which is that I studied them. I collected all the mice in the capital city of the islands, which tends to be the port.
which tends to be where new animals get introduced all the time. So even though the island had only had mice for a few hundred years, the mice I was looking at, their ancestors could have been, you know, 10 years old or 20 years ago that they were introduced. So I went about it all wrong. If I had to do it again, I would go to the farthest part of the island from the port.
Keller Kramer (20:00)
Thank
Steven Austad (20:03)
hoping that those are the animals whose ancestries had really been affected by the last few centuries on the island.
Brent Valentine (20:14)
Yeah, no, that may sense.
Keller Kramer (20:17)
Looking at, I guess, not so much environmental factors, but between genders, are there differences in the rate of aging or the way that aging occurs between genders?
Steven Austad (20:28)
Yeah, well, that's a really interesting question. So women live longer than men and they live longer than men pretty much everywhere and at all time. Anytime we have decent birth and death records and we examine them, women live longer than men, whether they're hunter-gatherers or whether they're modern Europeans. We don't really understand the
basis of it though, surprisingly. the thing that's so interesting is that it's not due to one thing. It's not due to the fact that men get heart disease. You know, they grab their chests and fall. It's not due to cancer. It's every disease, every top cause of death that we know about with one exception in humans, men die at a higher rate than women. And they also die at a higher rate when they're young, when they're old, even prenatally.
for prematurely born babies, if you're a male baby, you have a higher chance of dying than a female baby. I mean, we don't understand this at all. The one exception, and it's quite a glaring exception, is Alzheimer's disease. Again, for reasons that we don't understand at all, women are more prone to Alzheimer's disease. And it's not just because they live longer. If you compare men and women of the same age.
women are about 70 % more likely to get Alzheimer's disease than men. Now it seems to me that there ought to be clues into what's causing this sex difference by focusing on this big exception. So I wish there had been more focus on this, let's say the people studying Alzheimer's disease, but they haven't really appreciated, like we didn't really appreciate it. Even those of us in the biomedical field didn't appreciate
these sex differences because for the longest time we only studied men. We only studied males. You know, I was actually writing a book chapter once and I decided to, well, let's look at the difference in how long male and female rats and mice live. And I couldn't find hardly anything on it at the time because there were only male studies on males. You know, it took me the longest time to track down these obscure studies that had looked at both sexes.
the, so, so there's women have a survival advantage. That's, that's pretty universal, you know, all times, all places when times are good, when times are bad, ⁓ when they're young, when they're old. But the interesting thing is, particularly later in life, women are as healthy as men. They, ⁓ they're more likely to be disabled. They go to the doctor more often. They take more medications and more likely to miss work.
to go to nursing homes, you know, there's like six women, you know, ⁓ per man. And that seems a bit paradoxical. If they're so good at surviving, why aren't they better at staying fit? Some of it I think may be ⁓ basically a survivor's advantage. So the men, the less robust men have died, you know, and it's only the more robust men that are still alive.
Keller Kramer (23:30)
you
Steven Austad (23:56)
at those ages, that's one possibility. But I think there's likely more to it than that. But again, we don't understand that. mean, we even, it's only been the last 10 years we've appreciated that men and women experience pain differently. There are actually pain mechanisms that differ between men and women. you know, and there are ⁓ drugs that work very well, certain kind of pain for men that don't work at all for women.
And I could just see the male doctors going, now, now, now, now, little lady, we know this really is helping you, even though now we know it really wasn't necessarily helping her.
Brent Valentine (24:41)
Yeah, even the same with heart attack symptoms. They look different between the two.
Steven Austad (24:45)
Yeah, yeah, yeah, exactly.
⁓ yeah, it's, it's amazing that that that it took that long for people to appreciate that there are really robust differences in the way we age. And in fact, one of the most startling things to come out of the last 10 years of research on mice, where they've discovered now about a dozen drugs that make mice live longer.
Brent Valentine (25:00)
Yeah.
Steven Austad (25:15)
in the laboratory. About three quarters of those only work in one sex. They don't work in both sexes at all. They only work in one sex. Usually it's the males. ⁓ And that was a complete shock to everybody. Nobody expected that because in mice at least, there's no clear, mice don't have the same kind of female survival advantage that humans do.
Sometimes males live longer, sometimes females live longer. It's hard to predict. But yet, there are these drugs that by golly, they only work in one sex. And that's one of the things that my lab is interested in now, and we're trying to do some work on.
Brent Valentine (26:01)
Yeah. And then on this note of differences still, you mentioned like looking at the cartilage tissue in one of studies and what exactly are you looking at? Like, is it deteriorating? Is it breaking down? And like, how does the different different tissue types age if you're looking at like those like more hard metrics?
Steven Austad (26:18)
Yeah, that's a good question.
Do all the tissues age at about the same rate or do we have some tissues that age fast and some tissues that age slowly? Usually the tissues that are most vulnerable to aging are the tissues where there's the lowest amount of cell turnover. So if you look at your muscles, your skeletal muscles or your brain, most of the cells in your brain cells, the actual neurons there,
are the same ones you were born with, which means that ⁓ they've undergone a lot of wear and tear, you know, over the years. So there are some things that the cells really are breaking down from the inside because they've had, you know, they've accumulated damage for decades. Other cells like skin cells, you you're shedding those all the time. They're turning over all the time.
You know, if we could see this, we'd have this little cloud of sheds, skin cells around us all the time. how, you know, it's how things like dogs can track people. You know, they, they actually are smelling these, these cells that have been shed. that means that you have those cells are new all the time. And so those are cells that are typically in really a good condition. But what happens for cells like that, there's that much turnover. They're very vulnerable to cancer.
Because every time a cell divides, it increases the chances that there's going to be a mutation that gets fixed during the division. And over time, those things accumulate. So there's a fairly good relationship with the rate at which cells are turned over in the tissue and how susceptible that tissue is to cancer. So it's another one of the things that just some species are very resistant to cancer. Some species are quite cancer prone.
And that's kind of intimately linked with aging. Usually species that are cancer prone get lots of diseases early on. And it may be because the cancer suggests that they're not going to live very long no matter what. So nature doesn't invest in a long-lived heart or a long-lived eye lens or a long-lived immune system.
Brent Valentine (28:39)
Yeah, that's super interesting.
Keller Kramer (28:42)
Is there a relationship between the size of an organism and the rate at which it ages? Obviously with the example of the possum, maybe that's an exception to the rule. ⁓ But generally, do we know that dynamic?
Steven Austad (28:54)
yeah. Yeah. I mean, there's a very robust relationship between size and longevity between species. OK, so if you look at a mouse versus a dog versus an elephant, for instance, there's a huge difference in how long they live. Having said that, there's also a lot of variability. So for instance, opossums. ⁓
are much, shorter live than an average mammal of that size would be. We're considerably longer live than an animal that our size would be. And that's an interesting way to sort of identify things that are resistant to aging is to look at how different they are from what you might expect from their body size. And it's not just mammals this size.
Longevity relationship is true of birds, true of reptiles, it's even true of clams ⁓ and salamanders, pretty much everything.
We have some pretty good ideas about what that might be about. Going back to our thing about the hazardous, the hazardousness of an environment, you could imagine that a larger animal, just by virtue of its size, lives in a safer environment because there are fewer things that, if you're predator, certainly that can get it.
They typically are more resistant to extremes of temperature because of the lower metabolic rate. That's probably part of it. But the really interesting things are probably things that are exceptions. The small things that are really long-lived and even the large things that are really short-lived. Although it's not so easy to find those.
Brent Valentine (30:50)
Yeah, would those be more examples within a species like dog, larger dogs typically living shorter or like larger humans typically living shorter?
Steven Austad (31:00)
Yeah, well, it's really interesting that contrast between species pattern, which larger animals live longer and the within species pattern. And we don't have this for a ton of species, but for the handful of ones that we understand well, like dogs, like mice, like horses, it's the opposite, that smaller individuals tend to live longer.
We're not exactly sure of that. We know it's not due to metabolic rate because the smaller ones, if anything, have a higher metabolic rate. ⁓ That's a really, really interesting question. One of the things that is true in mice, and we're not sure if this is how widespread this is, is that the best way to make a mouse live longer is to disable growth hormone. ⁓
You know, can disable it in a variety of ways, but no matter how you do it, they seem to live longer. And of course, if you disable growth hormone, they're going to be a lot smaller. Now, whether that's true across species, we're not sure. Certainly, you know, women live longer than men and women on average are smaller than men. Is that an important contributor or not? ⁓ You'd think we'd have good solid answers to that since we have
millions and millions of birth and death records and ⁓ sizes of people. But I've never read anything about that except unusual papers that did compare Hall of Fame baseball players to women, Olympic athletes, some very specialized situation like that. But I keep thinking this is something that I should put some students into.
into looking into because like I say, the data have got to be out there. One thing we do know looking within a sex is that in humans, there's a very slight advantage in terms of cancer being smaller. And that's probably because you have less cells in your body that are at risk. know, any cell potentially could become
a cancerous self and has enough mutations in it. So if you have fewer cells, you know, that's less likely to happen. For some reason, taller people tend to be less likely to have heart attacks. These things almost balance balance out. So there's not a real clear relationship between size and longevity in people. If you ignore the sex difference, you know,
One study will find a slight advantage of one sex or of height and the other will find an advantage of smaller height. So anytime I see lots and lots of studies coming out to conflicting results like that, it makes me the effect if it's there is very small. Otherwise, we'd have a clear answer.
Brent Valentine (34:17)
So have you?
Thought about the idea of hormesis or some proper stressors that might actually be aiding longevity or allowing people to have the optimal amount of stress. One idea I think about with this is with working out and having more muscle mass, allowing a longer lifespan because maybe you don't fall and break your hip or get exposed to those things or you have better cognition. How do you think through that idea?
the optimal amount of stress.
Steven Austad (34:53)
Yeah, that's I, I actually am a big fan of the hormesis concept. ⁓ I think it's probably too, not just, ⁓ things like working out, but I think something like dietary restriction may be something very similar. Fasting may be something very similar. mean, ⁓ so it, wouldn't surprise me at all if it turned out that the, that there's a, well, for sure.
we all have an optimal level of exercise, let's say that would be good for us. The thing is, it's probably different for each of us. But the fact that it might be giving us just that right amount of stress and that that might be beneficial. I mean, we know certain kinds of stress, they wake up protective mechanisms, you know, or they perk up your immune system, they perk up your DNA repair you know, processes, they do.
a lot of stuff. So I think that that's likely behind a lot of these things. It's one of the reasons that I think, you know, it used to be all we knew about making things live longer was making them eat less. In recent years, it's, I think it's pretty well accepted now that a lot of that effect had to do with just fasting. I know I've done a lot of these studies in mice.
And I'm sort of kicking myself now for never thinking about it. But when I have a mouse that's on, that I'm restricting its diet, when I feed it, it eats all its food in, you know, 30 minutes, 45 minutes. So I don't feed it again until the same time the next day it's fasting for 23 hours. And I never thought about that. I was just thinking about it, the total amount eaten, but now it looks like it may be the fasting period that is the important thing.
because we know after about eight hours, fasting turns on all kinds of protective mechanisms. There's a real fasting physiology. And my guess is, one of the things that I did at one point in my career is I worked in very remote area of Papua New Guinea. Among people who are still hunting with spears and arrows and things. And they pretty much eat once a day. And they might go several days without eating if they don't happen to be lucky.
honey things. So I think for most of our history, you know, when we got the next meal might've been a little bit uncertain. And it may be that this fasting is just returning us to something that our bodies, you know, evolve to cope with. ⁓ because it is, it is really interesting now that we have all these faddish fasting diets, you know, some people, you know, only eat
during a certain time interval and some people fast once or twice a week or maybe twice a month or something. And ⁓ at least in mice, it looks like those things confer a lot of benefits, that kind of thing. And wouldn't surprise me if that's true in people as well.
Brent Valentine (38:11)
Yeah. Do you have like an idea of like optimal amounts of fasting? Because obviously I think too much you would limit like muscle growth or other different like adaptations. I'm sure there's an element of if you fast too frequently, you have like other adverse effects. Like kind of where's that balance?
Steven Austad (38:33)
Yeah, well, that's really good question. And the short answer is we really don't know where that balance is. you can, particularly with time restricted feeding, you know, if you say, okay, you can eat all you want, but you have to confine it to between 10 in the morning and let's say six at night, then you're probably going to be able to maintain a fair amount of muscle mass. ⁓ But you're still waking up
all that fat, fasting physiology. So I don't think that it's, it's necessary to, ⁓ to basically become frail, which, know, there are these people that saw the dietary restriction literature and mice and think, aha, we need to do that ourselves. And they put themselves on these incredibly low calorie diets. And, know, I've been to meetings where there are bunch of these people around and they're very frail. They have no muscle mass.
whatsoever. They're cold all the time because their thyroid is not producing enough ⁓ thyroid hormones. ⁓ And that's one of the times that I think translating things from mice to humans is really a bad idea because ⁓ they're always in fact, they're always urging one another, let's, we got to exercise more. We got to try to go back to muscles, but they can't because that makes them hungry and they don't want to eat.
You know, and so you end up with people that are very thin. have poor bone quality because they're eating so little and particularly that they consume quite a little protein. And then the other thing is that they don't get any exercise. So I end up with weak muscle, poor bone quality. That probably doesn't matter so much if you're a mouse living in a cage, but if you're human living in the real world, it's not good.
It's not good. know, you're more likely, particularly as get older, you're more likely to fall if you don't have the muscle to prevent it. And if you do fall, you're more likely to break something. So, ⁓ so yeah. Now, interestingly, if you're talking about real extreme exercisers and you look among the most successful aging people, the people who live to be
100 and are still healthy at 100. You don't find really extreme exercisers in those groups. so, I mean, I think that makes your point, Brent, that there's probably an optimal amount of exercise and you can overdo it. It's just that we don't know what that is. And it probably differs depending on, you know, your particular genetic background.
Keller Kramer (41:31)
And does the idea of hormesis extend to, I guess, more abstract ideas, like especially in humans of more cognitive stress or setting goals and doing hard things that might not be measurable in, I guess, more scientific measure?
Steven Austad (41:49)
Well, that's an interesting idea. I hadn't thought about that. But ⁓ I think anybody that's been a college student is hoping that stress is good for them because there's finals that comes around very regularly. And certainly for those of us who've lived on in academics, we hope the same thing. But I think cognitive stress is, it's always been assumed to be bad for us.
I don't think it is, you know, there's the kind of type A personality, you know, stereotype that people that are stressed all the time are going to, you know, die of heart attacks. I don't think that's really been born out by a great deal of data. And if you look at it, high achieving people tend to live a long time relative to the normal population. And we don't typically associate it to the fact that
They've had to do whatever they had to do to be high achieving, but it's a pretty dramatic thing. know, there's, you know, one of the things that I hear from people who are worried that these people that are trying to keep us healthy longer are doing something that they shouldn't do, something that's unethical. say, well, what if this, these, these interventions you're developing are expensive and only the rich can afford them. And then we're going to have two classes of people. We're going to have the rich.
long life people and the poor short life people. And my response is, we already have that. That's here right now. Having a better education or more money, you stay healthy longer. ⁓ And some of that's differences in lifestyle, but a lot of it is stuff that we don't know about. There's a big effect of education. People with higher levels of education live longer.
We don't really understand why that is, you might be on to something there, Keller.
Brent Valentine (43:53)
Yeah. And I think kind of transitioning a bit to some of the issues you've brought up with how aging research is conducted. think some of that, Keller's last question was about the enrichment in cages and this mental stimulation and that, but before we fully transition to that, just like what are some of the major issues in aging research and some of your qualms with it?
Steven Austad (44:21)
some of the major issues about what?
Brent Valentine (44:25)
⁓ aging research and the way the research is conducted.
Steven Austad (44:28)
What
are the major advances, the most promising areas or the issues that might be problematic in the way that
Brent Valentine (44:40)
Yeah, the problematic issues.
Steven Austad (44:42)
Yeah, well, I do think there are some real problems. again, I think this comes from my background in field biology that I've started thinking about this. But we put these animals in basically cages the size of a shoebox, we give them no stimulation at all, because we assume that they're that they're non sentient, you know, just like little machines. And we feed them the same food we give.
same light cycle every day, absolutely nothing. We might put a wheel in their cage and they might run for hours on this wheel and we think, well, that's great. Well, why are they doing that? Where do you think they're going? Animals are sensible and we know from a lot of research that if you give animals just a little bit of variety, a little bit of enrichment in their cages,
It changes everything. It changes the structure of their brains. It affects their immune system. It affects their proneness to disease. One of my ⁓ studies I like to mention is a study of mouse versions of Huntington's disease. Huntington's disease is about as pure a genetic disease as we know about.
But, and we know how to replicate it in a mouse because we know the gene that's involved and we said take that gene and we manipulate it in the mouse and they get something very similar to Huntington's disease. But if we give them a little bit of enrichment, that doesn't come on. That disease doesn't come on for much longer time than in animals that are just in the normal cage. So I think, and then we also do things like, we might start off with five.
mice in a cage, let's say, ⁓ because that's the way we save money. Most universities charge by cage number. But as the animals die, there's fewer and fewer. And by the time there's one animal left, we don't think about, well, what's the effect on that animal of having had all these cage mates for its whole life, and now it's by itself? ⁓ So that's one of the problems. The other problem, and this, think, is
really a significant problem, is that for a long time, until about the 1960s, it was so difficult to get studies to replicate in one part of the country and the other for longevity. And it turned out that a lot of that had to do with the fact that they had different pathogens. They had different microbiomes in those parts of the country. And to combat that, we started
trying to control the microbial access that they had. We created these, what's called specific pathogen-free animals ⁓ to protect them. And that was successful in making studies more easily replicable. But what we didn't really realize at the time is that in order to control the access by these things we didn't want them to have, we were also keeping them from having a normal microbial experience.
We weren't exposing them to normal things. And over time, this has had a tremendous impact on them. Mice in cages have immune systems like newborn babies do, which is to say they don't have much of an immune system. And you can tell this if you just take a laboratory mouse, particularly an older one, and you put it in a cage that had perfectly healthy pet store mouse in it, and you wait.
And within a few weeks, they die. And that's because it's just like when Europeans introduced all these novel diseases into the new world and we killed off a huge fraction of the indigenous people here. And so because the immune system is so critical to the way that we age, I think this is a huge gap in the way that we do studies.
Putting our study animals in more realistic environments, more like the environments in which they evolved, will teach us a lot. And it might make us absolutely dismiss some avenues of research that we think are really promising now, because they're promising in animals that have this highly artificial environment. But in a more realistic environment, ⁓ the animals don't
do so well. One of them might be dietary restriction. know, ⁓ like I say, that's very robust in mice and rats and flies and everything else. But the results in people are not really very impressive. And in fact, ⁓ I haven't seen any of my friends in the caloric restriction society, which was really a society of people who did this since COVID. But I'm wondering how they did.
in COVID, you know, particularly the older ones, because we do know that, you know, starvation is an immunosuppressive. And ⁓ so ⁓ I'm very curious about that. By the way, I do have one anecdote about this dietary restrictions stuff, because I think it's funny, I was involved in a TV show a number of years ago. And one of the people that was on this show was a guy that was diet.
dieting the way that mice was. He was eating like 30 % less than he wanted to eat. He's one of these frail people. He was a computer nerd. He did war games. And so he had a program. He recorded everything in the world that he ate. So he really, really did this. And they wanted to have him doing something active to show how healthy he was. And they said, well, how about if we just, can we film you swimming across a swimming pool? And goes, sure.
And he almost drowned. mean, you know, he had, he had no body fat whatsoever. Also no muscle and he sunk pretty much like a rock. mean, he really labored to swim one lap of this thing. And then they sent him out to get a complete medical exam. And the doctor said, you have really good cardiovascular health. Your, your, your veins and your arteries are really clean, you have great blood pressure.
you have undetectable testosterone. And this was a guy who was probably 45. He should not have had undetectable testosterone. ⁓ That's another ⁓ side effect of that level of caloric restriction, which probably doesn't translate too well for most of us. And by the way, he didn't want them to mention that on the show as well. So they didn't. ⁓
Brent Valentine (51:50)
Yeah, that's eye-opening.
Keller Kramer (51:51)
Well.
Steven Austad (51:55)
Yeah.
Keller Kramer (51:56)
It seems like
with a lot of, I guess, your argument for changing experimental design, like it seems very logical. I guess I'm more curious, like what is some of the pushback against it? Is it largely just the fact that it has been more difficult to replicate? Because I would imagine striving towards more, I guess, a higher conversion between preclinical and clinical trials would be kind of the ideal.
But yeah, what are some of those arguments against it?
Steven Austad (52:28)
Yeah, ⁓ I the main argument that I hear against it is, well, we've been doing it this way. And so that's the way we should continue to do it. the more serious thing is, I mean, there is this issue. OK, so if this colony has these particular microbes and this colony has that, how are you going to replicate your experiments? And my answer to that is, we're not trying to, you the goal of this research is not to make
laboratory mice live longer in a laboratory. It's to make humans stay healthy longer. And if you look at the range of environments that we live in, the things we're exposed to, some of us eat healthily, some of us don't, some of us exercise, some of us don't. We have different genetics, we're exposed, we live in this sort of microbial soup all the time. I think what we should be effecting, we should be concentrating on is things that work under any conditions.
If something only works in this person's laboratory, but if you take it out and you do it in a field and the effect goes away, that's not a very interesting result to me. It might be interesting for ⁓ isolating some specific mechanism that's going on. But in terms of identifying something that might be keeping people healthy longer, I think we want something that just works under pretty much all conditions.
Brent Valentine (53:54)
Yeah. And then also looking kind of into the future of like where you hope to see the research going. What are some of the different animal models that you are trying to advocate for? Cause I know the latest book you're looking both at like land animals, aerial, aquatic. What are some of like the most promising new models that you hope get popularized?
Steven Austad (54:16)
So
I think the one that's got the most promise, that's the least exploited at this point, because we are starting to look at some of the longer live, healthier models like the naked mole rat, the blind mole rat and all. The one glaring thing that nobody seems to be paying attention to are the birds. birds are a lot longer lives than mammals of the same size.
And they're longer live despite the fact they have a higher metabolic rate. have a higher body temperature. have ⁓ diabetic levels of blood glucose, all of these things. If we saw them in an animal, we would think that's going to be the sickest, shortest-lived animal in the world. Yet they live three times longer than mammals, and they're common. And why nobody's really taken it seriously to figure out why a little mouse-sized bird
can live 20 years in the wild when a mouse itself can live two or three years in the best conditions we can provide. I'm just shocked at that. And I keep thinking somebody is going to do a Manhattan project to try to understand bird longevity. The other thing about birds is ⁓ because of the physical demands of flight, they are healthy pretty much to the end.
You know, even veterinarians who treat birds will say it's difficult to treat birds because you don't know they're healthy. They're fine. They're fine. They're fine. They're dead. You know, and but that's pretty much what we'd like for people to be right. You're good. You're good. You're good. And boom, you know, it's like a light bulb. You know, you're fine. And then it's gone. So to me, this is the end. You know, there's 10,000 species of birds. There are some really common ones.
Some of the really common ones live a long time. It's just a study that's begging to be done, but it's kind of, it's hard to get funding for these wild ideas, which, you know, to me, they're not that wild, but the people that think that every mammal is either a human or a mouse, then they're pretty wild.
Keller Kramer (56:37)
And does the interest in birds that isolate to just birds of flight or does that kind of all types of birds? Cause I imagine birds of flight have the advantage of they can kind of escape a lot of predation.
Steven Austad (56:44)
BOOM!
Yeah, very good point, Keller. So yeah, if you look at the birds, like I say, on average, birds in the wild are three times as long as mammals in zoos in captivity. But if you sort of break it down into groups of birds, there's a real advantage of the ones that fly, probably for that evolutionary reason that by virtue of flight, they live in a safer environment. They're protected from lot of dangers on the ground.
If conditions deteriorate locally, they can move a long ways fairly quickly. And it turns out the birds that are weak flyers are not particularly long live. So things like turkeys and chickens and quails that, you know, they could fly if they really have to, but they don't do it very often. They're among the shortest lives of all the birds. So what we really want are the ones that are ⁓
that live a long time and are robust flyers. There are these birds that fly from sea level over the Himalayas in a day. And if you just think about that, we think about somebody trying to climb Mount Everest, they have to prepare for months and have all this equipment and all these birds in a day. They do it. They climb up to 30,000 feet, fly over the Himalayas, land.
and then have enough energy left to make. It's incredible.
Brent Valentine (58:29)
And then kind of extrapolating further, we saw you have a bet with another professor that there's already a person alive today who will live to 150 years old. Do you think that, is that bet predicated on further advancements in technology, understanding certain insights from some of these different animal models? Or do you think like this is just the nature of...
like current medical capabilities, will take us there.
Steven Austad (59:03)
Yeah, that's a good question. No, I think it depends on us finding out some way to actually slow aging. don't think we sort of chose 150 years and only one person has to live that long. So it's one woman really. ⁓ We chose that because we thought getting better at what we already do pretty well, which is diagnosing and treating diseases is not going to get us there.
it's going to require some dramatic change in the way we understand aging and the way that we can medically target aging. And one of the things that we discovered in the last 15 years when we're finding more and more and more ways to keep mice alive longer is that a lot of these things can be started relatively much later in life than we originally thought. Used to think that in
dietary restriction, for instance, the earlier you start it, the bigger the effect you get. Well, in some of the drugs that we've discovered, it seems like you could start it relatively late and have a pretty big effect. yeah, so our bet comes due in 2150. So someone had to be alive in 2001 that's going to 150 years. Well, I mean, for people that were born at the beginning of the 21st century, they're only 25 years old now, you know, so they have
a lot of time for us to come through with breakthroughs. And if you think about it, it wasn't 150 years ago ⁓ when we started flying. We've only been flying for 120 years. And yet, we went from barely getting off the ground over an open field ⁓ to going to the moon. We did that actually in 70 years.
By the year 2150, actually by the year 2050, given the way that progress is being made in the field now, I think we're going to have some real treatments.
Brent Valentine (1:01:13)
And you think it's treatment dependent and not really good preventative care and delaying aging.
Steven Austad (1:01:20)
Well, what?
Yeah, that's a good point. What I'm calling a treatment really means that intervention, because it's we're really talking about preventative approaches here, not the way we do medicine now, which is wait until you something's wrong and then try to fix it. But what I'm talking about is something that prevents things from going wrong in the first place, something that the way people think about vitamins today.
You know, people take vitamins to prevent them getting something, even though vitamins for the most part don't have any impact on that. Still, people take them in the hopes that they'll prevent them from getting X or Y or Z. And that's really what we're talking about. We're talking about really changing the way that medicine works, that you take your medicine before you get sick so that you don't get sick rather than waiting to get sick and then seeing if you can fix it.
Brent Valentine (1:01:51)
Mm-hmm.
Yeah, this is like a true pharmacological solution, unless like really like proper diet, nutrition, all the cold plunges you could possibly do. Like none of those things would max out to 150 years.
Steven Austad (1:02:31)
I don't think those would get us there, but
I think those things plus pharmaceuticals could do it. And that's something we can't do in our laboratory mice. can't basically, we don't give them enough exercise. You we think of, we give them a little wheel that they run around, you know, we're getting exercise, but we have no clue as to if you do everything else right, you have the best diet, the best exercise regime for all that stuff. Plus then you get as well.
something that addresses the aging problem, that could have really much more dramatic effects than we see even in laboratory mice.
Keller Kramer (1:03:11)
Yeah. And kind of as we wrap up here, are there any common misconceptions in the longevity or aging space that you've seen become more popular in recent years that you'd like to either add nuance to or maybe dispel?
Steven Austad (1:03:27)
Yeah, well, mean, yeah, there's a huge amount of hype out there. I mean, it's overwhelming. There's always been hype in longevity research, right? 2,000 years ago, people were saying, you take my potion or my ointment, you're going to stay young forever. Well, now there are dozens and dozens of people saying that on things with absolutely zero evidence about it.
I should start keeping a list of these things because they pop up on my social media feed all the time. And it's so tempting for me to spend all of my time making comments on those, but I don't have time. But yeah, mean, wear this thing around your head, you know, and plug it into a socket. mean, you know, take this pill. It's just crazy stuff. ⁓ Yeah, it kind of drives me.
Keller Kramer (1:04:16)
You
Steven Austad (1:04:24)
crazy now because some of it is like possible but unprove it. But some of it we already know it's completely bogus, it doesn't shame people into not trying to make a buck out of it. Even my own family, my wife. So I studied these clams that lived 500 years in time. She wanted me to market some product with that, the clam juice from that of cosmetic or something.
And I say, you know, if you're a scientist, all you have is your reputation. If you lose your reputation, that's it. So, you know, I've resisted ⁓ doing anything like that, but I don't spend my full time debunking stuff, but I probably should. You you could, you could spend a life just debunking nonsense is out there in the aging space.
Keller Kramer (1:05:15)
You
Brent Valentine (1:05:22)
Yeah, so there's no supplement, nothing we can take for now that will extend our life.
Steven Austad (1:05:26)
Nothing that we could say
we know works. There's lots of stuff that you could take. There's lots of people taking rapamycin. There's lots of people taking metformin that don't have diabetes. It might be doing something good for them. Those things are at least possible. Some of the other things, wearing a strap, electrical strap around your head, where you know that those are not going to do anything.
Keller Kramer (1:05:55)
You
Brent Valentine (1:05:57)
Yeah. Do you think GLP-1 agonists will help extend lifespan potentially?
Steven Austad (1:06:06)
GLP Agonists, the GLP One Agonists are really interesting. I made a joke when the first, I don't know if you guys have heard of the X Prize HealthSpan, but that's a, you know, that's an $80 million prize for, you haven't heard of that. Oh, you gotta have the person that's in charge of that on. So it's it's a $101 million project to try to get.
people to get the restoration of function of their immune system, their muscles, and their brain to the equivalent of 20 years younger than they currently are. And if you're successful at that, the grand prize is $81 million. So that's a huge motivator. But
Now I actually lost track of the original thing that the question that you asked.
Brent Valentine (1:07:04)
just the GLP-1 agonist.
Steven Austad (1:07:06)
Yeah. So I made a joke when that was, so I'm on the scientific advisory board for that prize. And when we first did it, we're trying to get publicity for the prize. I made a joke on, on, on X. said, well, I'm going to win the prize. Now it's going to be GLP one plus growth hormone because GLP one's kind of inhibit muscle building. I said, growth hormone. was just a joke, but I got this incredible response to it. But now I'm thinking, well, maybe it wasn't such a joke.
Cause we keep finding out more and more and more benefits that these GLP-1 agonists have. And it's quite embarrassing that the aging field didn't come up with this. You know, was the diabetes people that came up with this drug, but it's incredible. But I have to say, the design of those drugs was inspired by a Gila monster venom and Gila monster live a long time.
So it just sort of makes my point that by studying these animals live a long time, we might come up with answers that we wouldn't come up with just by ourselves.
Brent Valentine (1:08:18)
Yeah, definitely.
Keller Kramer (1:08:20)
And as we wrap up here, do you have any advice to the listeners about how to live a healthier life, career, or just anything in general?
Steven Austad (1:08:30)
Well, I would say your health is important when you're young as well as when you're old. So if you want to live a long, healthy, successful life, you want to start when you're young. You want to be in good shape. When we get the drugs, when you eat the drugs that are really going to help you, you want to be in good shape as you can at that point because they'll be able to help you the most. So I just say, pay attention to all of the things that we already know.
are beneficial to our health, including our mental health. ⁓ And just wait, because something's gonna come down the pike now that's gonna change everything and it's gonna change everything overnight.
Brent Valentine (1:09:15)
Looking forward to seeing that. Perfect. Well, thank you for coming out today.
Steven Austad (1:09:20)
Okay, was great talking with you guys. Good questions. I enjoyed your questions a lot.
Keller Kramer (1:09:21)
Thank you.
Brent Valentine (1:09:27)
Thank you.