49: Aging, Longevity, and Animal Models with Aubrey de Grey

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Hosted by
Will Jarvis

In this episode, we chat with Aubrey de Grey about Aging, Longevity, and Animal Models. Ever wondered why opossums live 1.5x as long on a remote island on the Outer Banks of Virginia? Why do Tortoises live so long? Why is breathing so bad for us? And what the roadmap for treating aging looks like. 



Transcript:

Will Jarvis 0:04
Hey folks, I’m William Jarvis, along with my dad, Dr. David Jarvis. I host the podcast narratives. narratives is a project exploring the ways in which the world is better than it has been the ways it is worse in the past or making a better, more definite future. I hope you enjoy it.

If you enjoyed this episode, please subscribe. You can get on our mailing list, find show notes, transcripts, as well as videos at Nerdist podcast.com. Thanks. Well, Aubrey, how are you doing today?

Aubrey de Grey 0:45
I’m well, thank you. How are you? And thanks for having me on the show.

Will Jarvis 0:48
I’m doing great. And I really appreciate you coming on. Before we get jump into it, could you just give us a brief bio and some of the big problems you’re working on?

Unknown Speaker 0:59
Sure, yeah. So I am a biologist. I’m the Chief Science Officer of a nonprofit based in Silicon Valley, called central Research Foundation. And what we do is we work on the early stage translational research, to develop new medicines that will postpone very greatly, we believe the health problems of late life, we believe that it’s possible to repair the various types of molecular and cellular damage that the body accumulates during life. And thereby to stop that damage from reaching a level that exceeds what the body is set up to tolerate. That’s basically all that we do. But of course, when I say all I mean, it’s a big job, we have lots of different types of damage that accumulate in the body, and any one of them can kill you on its own, more or less on schedule. However, while we’ve explored the others, so this is very much a divide and conquer approach. Over the past few years, some of these technologies have moved along far enough to be you know, within striking distance of clinical application, which has allowed them to be picked up by the private sector, investors who don’t just want to live a long time, they also want to make money, you know, those people are getting interested. And that’s enormously important, because investors, you know, they tend to write bigger checks than donors do. So the projects end up going faster, we could wonderful, but there are still some projects that are not far enough along to be investable, even in the eyes of the more courageous investors that are interested in early stage high risk, high reward stuff. So we as the nonprofit sense Research Foundation, not in any danger of you know, declaring victory anytime I

Will Jarvis 3:04
got it. I really liked that. And did you have like, a specific aha moment when you realized aging was the big problem that you needed to work on? Or was it kind of a more gradual thing over time?

Unknown Speaker 3:17
It was pretty much an aha moment. Essentially, what happened was, I was about 30 or so. And I, for a couple of years to a biologist. Now, for the previous, probably 15 years, I had not I had found that the right thing for me to do was to dedicate my life to the problem of work. In other words, the fact that, you know, people have to spend so much of their time doing stuff that they would not do unless they were being paid for it. That’s a big problem, I believe, you know, it causes a lot of suffering. But I never thought that it was anywhere near as big a problem as the problem of aging Far, far bigger. Surely. The thing was, it was a question of where could I make the difference? When I was 15 or so I started programming and I thought, I’m good at it. So I felt you know that where I should be putting my effort into artificial intelligence, that well develop software that can automate the tasks that most of us don’t want to do. And I was perfectly happy doing that I was doing well. But then I met and married biologists, as I mentioned, and gradually over the few years, after we married, I began to realize that we will ever talking about aging. And I started asking you increasingly, you know, strident questions about this. And say, you know, you know, Aren’t you interested in aging? And she would say, Well, no, I would say why not? And she would say, Well, you know, it’s just decay, isn’t it? We’re not going to understand any fundamental truths about the universe by studying decay and And I would say, well, maybe that’s true. But so what really because you know, it’s bad for you. And she would say, well, that’s not my problem. And I would say, well, hang on it kind of is. But that would be about five we would get. And pretty rapidly, I began to be aware that the other biologists I was meeting through her felt the same way. So you know, it did take a little while longer than that, for me to really come to terms with this, this revelation, this bombshell that most people actually are perfectly happy with aging, or at least they’ve made their peace with it. Because, you know, it was always so obvious to me that this was a problem that was a medical problem, and it could in principle, be solved. So eventually, I found a way to switch fields, and here I am.

Will Jarvis 5:45
That’s excellent. Do you think people have missed aging as a problem, because there’s a certain amount of fatalism to it that, you know, it’s just, it’s gonna happen, there’s nothing we can really do about it. And because you haven’t considered there’s a possibility, we could do something about it. And we’re just like, Oh, it’s natural, it’s gonna happen. It’s nothing to worry about? Well, I mean, let’s,

Unknown Speaker 6:08
I would say that it goes both ways to bi directional thing here to kind of feedback loop. Because, yes, absolutely. People are fatalistic about aging, and they don’t think that it worked. But that’s because they don’t think it’s possible to do anything about it. So, you know, it kind of makes sense that if you’re, if you’re aware of this terrible gossipy thing, it’s gonna happen to you at some point in the relatively distant future. And then absolutely nothing you think you can do about it, then the right thing to do is to trick yourself into pretending that it’s some kind of blessing in disguise, right. Or at least that it’s woven into the fabric of the universe. And so that, you know, because that way, you’ll be able to put it out of your mind and get on with your miserably short life and, you know, make the best of it, rather than being preoccupied by this thing. And, you know, people that make men troublemakers, like myself come along, and they say, you know, we might be able to do something about this, you know, the big risk is getting your hopes up, and just can’t cope with that can’t cope with the idea that they might actually decide maybe they’ll be able to benefit from all of this, and then finding, you know, things more slowly than they were hoping and idea, you know, they’re not going to benefit after all. You know, I mean, I understand that not everybody can be courageous. But still, I feel that that is fundamentally the reason why everything’s been so slow in terms of public opinion, even as the science is moving forward at an accelerating rate.

Will Jarvis 7:41
Definitely, I think that makes a lot of sense. And it does seem like the science is accelerating a lot, especially in the last 10 years. You mentioned some of the, you know, there’s a lot of commercial efforts now, which is really promising, in my opinion, D has it been more difficult or easier than you expected when you first started on the journey, are about the same about like what?

Unknown Speaker 8:03
Well, some parts have been hit harder, and some parts have been easier? Well, I wouldn’t say anything has been easier, something would have been about as difficult as I expected. Essentially, the parts would have been as difficult as I expected, I’ve been the science, the actual development of the technology, that’s gone pretty much as flat as I would have expected, given the resources, the manpower that has been working on it, which is still inadequate, but was far more inadequate, until let’s say that for the past few years. The part that I was over optimistic about that I thought would go faster, was the funding, the persuading the public, especially, you know, a few highly, you know, technologically sophisticated, wealthy people, that this was actually something they should prioritize. I was definitely expecting that to go faster, especially starting in 2006. When I didn’t succeed in persuading one such person, Peter tail, to come in for a respectable amount of funding of philanthropic support for this work. I thought, you know, he’s really high profile guy, he’s got a great reputation, the other billionaires are going to be lining up, it didn’t happen. So that was my big case of over optimism. But if we take that out of the equation, if we say, Well, okay, you know, have we achieved pretty much the same rate of progress that I would have expected us to achieve given the amount of financial support that has eventually ended up being available, then I would say yes, we have, we have not had any new big bad surprises.

Will Jarvis 9:50
And that’s that’s really encouraging to me on one level and also discouraging, right because it’s like it The problem is, is almost the sales angle to convince people that you know, this is an important problem. So I think we should put resources behind

Unknown Speaker 10:01
it that way, actually well, because the thing is that the more progress you make, the easier that problem gets. So I already in the past few years have been a night and day chained from the previous decade or two that I’ve been working in this field, in the sense that there is now an investment community, a coterie of wealthy who are willing, who you know, they’d like not to get sick when they get old, but they’d also really like to make money in the making money part dominates their thinking. But they now think they can make money. The money is unevenly distributed at this point, but it’s a hell of a lot better than when there was no money at all. So in a sense, we’re kind of that we’re most of the way there, the the more people get on board with this get on the train, the better for sure. This certainly applies not only at the level of investors, but also at the level of policymakers and decision makers in government and so on. And that’s very much a work in progress. But the progress of the rate of progress is far better than it was even a couple of years ago.

Will Jarvis 11:15
Excellent. Excellent. And, and on the progress front, do you envision that there’s gonna be one big therapy we find that makes up most of the gains in reversing aging? Or is it going to be a basket of therapies that work on all kinds of different pathways,

Unknown Speaker 11:32
and absolutely certain, it’s going to be a basket of therapies, the the whole paradigm of trance that I’ve been pursuing for the past 20 years, and we could remains unequivocal in the most promising approach is intrinsically a divide and conquer approach. It’s way in which we enumerate a large number of different types of damage. And then we, you know, we we, we kind of cluster those many, many types of damage into a manageable number of categories. The way I do it involves seven categories, different people have come up with different numbers, but it’s really just the classification process. The purpose of the classification is simplify the process of developing Damage Repair therapies, rejuvenation therapies that eliminate these various types of damage from the body. The reason why the classification is possible is because you can do it that like for example, if you’ve got cells dying, and not being automatically replaced by cell division, you can use stem cell therapy to fix that to put new cells in that will replace the cells that the body is not replacing on its own. And, of course, you need slightly different stem cell therapies for different organs and tissues that may be may be suffering from this problem. But all stem cell therapies have an awful lot in common. So you want a couple of them working, getting the next one working on the one after that is very much more routine, easier and cheaper and faster. So that’s why the classification makes sense. That’s why the whole the whole divide and conquer approach is reasonable and plausible and feasible.

Will Jarvis 13:12
That makes a lot of sense. And I think it’s a it’s a really well thought out and get approach to the problem. Are there any animal models that are particularly interesting to you related to aging when I was a kid, there’s two animals that really got my thinking started on aging, so possums, you know, they live their only marsupial in North America, really common in North Carolina where I grew up. And they only live to be about a year old. You know, maximum lifespan is about two years old. And then the eastern box turtle, which was a really common turtle, we found on the road all the time, they demonstrate Negligible Senescence, and like this, this kind of dichotomy always saw, it was really interesting to me. Are there any other animals that you think okay, this is, this is a really good model we should look at more closely than we currently are to understand aging.

Unknown Speaker 14:01
Yeah, so right. So let me give a fairly elaborate answer to this question, because it’s a really great, interesting question. I don’t get asked it very often. So first of all talk about opossums. So they turn out to have a rather important place in the, in the history of the field of the biology of aging. Because, way back in the early 1990s, there was this guy, his name is Steve or stad. He’s now a professor in Birmingham, Alabama. He was a young guy, and he done a few other things with his life, including being a lion tamer. Yeah. Basically, he knew a lot about a lot of different animals. He was fundamentally a zoologist, and he decided to go into aging. And the thing you decided to do first was to test a theory of the evolution of aging. That explains not how particular species live longer than other species. Rather than why they live longer, where the evolution the selective pressure comes from that actually causes it to happen. So the theory in question was basically that extrinsic mortality drives it. So actually, mortality simply means all of the causes of death that a species may experience that do not have to do with how old they are, how long ago they were born. Alright. So, of course, a big one. In fact, the big one is predation. Right? Right. And so they’ve had this brilliant idea. He said, All right. So we don’t necessarily look at different species, because that’s difficult because you know, different species have been separated from each other. Now, phylogenetically for a long time, it will be marvelous if we could look at populations that are the same species. In other words, I’ve actually been interbreeding until recently. But you want to have them having not been interbreeding really recently. And so what he did was this extraordinarily clever thing. He looked at a passage, not actually in North Carolina, in Virginia, but close enough, right. And he realized that this was an opportunity because of the outer backs, the islands that exist off the coast of Virginia. Now, these islands have not been island for very long, they have been cut off from the mainland by tidal forces, okay. And some of them are quite big. He focused on one particular Island, which is just the right size to be able to support a population of opossums, but not to be able to support a population of the carnival that normally eat apothem later now, the higher up the food chain, you are the the larger an area you basically need in order to sustain a stable population. So this world it’s called SAP, SAP.

Unknown Speaker 17:00
with just the right side, we’ve got a bunch of opossums, and they’ve got no predators. Whereas on the mainland, where you come from, they’ve got masses of creditors, and then very, not very intelligent, so they really don’t live very long. So he said, Well, okay, evolutionary theory predicts that the apostles on this island are gonna live longer. It’s only been an island for something like 5000 years. So it’s 1000 generations of opossums, right? That’s a blink of an eye and evolution, okay. But he said, Well, maybe this is fast enough, maybe we’ll see something. And he shows how old it is the persons live more than one and a half times longer than the apartment on the mainland. So this showed that even in a natural environment, if you just remove the major source of extrinsic mortality, namely predation, then the response, in terms of the ability to age more slowly, is insanely fast. The only prior work that had been done in this area was in fruit flies. It had been done about 10 years earlier by professor who’s now I’m in California, Irvine, when he was doing his PhD in the UK, and he said the same thing. But he showed it with artificial selection, very artificial, he basically said, okay, you’re not allowed to reproduce until you’re already old. So he kind of imposed a very different kind of pressure. So it’s a bit more stable, a lot more artificial. So this is really important. The reason I tell the story in such detail, it’s not just a good a good story, only both land timing, and so on, but also because because it shows you that you can learn a lot about aging, by studying short lived species, not just long lived ones. But coming back to the question, you were really asking the long lived species? Yes, we can learn things, but exactly how much we can learn that actually really tricky. Because almost always, when a species is long lived, its long lived for a reason that does not extrapolate to humans. So in the case of tortoises, for example, yes, they live a long time, the reef, the evolutionary reason is exactly the one I just described that, you know, it’s hard to eat a tortoise because it’s got a shell. Right, right on time. But how do you know what’s going on in their cells in their organs that allows them to accumulate damage more slowly? That’s tricky to work out. And when you look, unfortunately, what you find out is that the main reason is that they are cold blooded. In other words, they just like they don’t have to breathe them, like if you and I do so. And breathing is really bad for you. This is a really, I mean, I’m not saying breathe, breathing, polluted, right? I’m saying You know, it’s really bad for you because the process of using oxygen in cells, which is used to extract energy from nutrients, that’s a really hairy process evolved exactly once a few, a few billion years ago. And it creates toxic toxic side products called free radicals, with damaged DNA and proteins and everything. So yeah, I mean, you know, breathing, it’s definitely very bad food. It’s the single worst thing you’re doing for your longevity right now. But unfortunately, it’s a bit non negotiable. And furthermore, you know, the amount of work that you do is very non negotiable, because we’re warm blooded, and we have to do more of it than what. So that’s the main reason why towards this live longer, why sharks live longer. It’s even the main reason why whales live longer, even though they are warm blooded, because the surface to volume ratio thing, the amount of heat you need to make depends on how rapidly losing heat through your surface through your skin. And the bigger you are, the less that’s going to happen. Right. So, so that so again, same deal, same deal for a very famous small mammal called the naked mole rat, which is also heavily studied by people who want to understand aging. They live naturally underground in the Kalahari Desert, in, in southern Africa. And, you know, back down there, it is warm all the time, the the temperature change between night and day is only about one degree Celsius. Right. So then after too much want my burning energy, to actually to keep warm.

Unknown Speaker 21:38
Now, thing, all of that, all of that, there are some things we can learn. So naked mole rats are actually a great example, because they have this insanely good defense against cancer that we only verify we understand at this point. And that’s a really important thing to understand. We might be, we might just be able to emulate it. Similarly, birds or birds tend to actually breathe out of the way do they’ve got a lot of energy involved in, you know, flapping, really. And that, you know, that is quite remarkable, because birds are small, you know, small birds, birds and rodents that are the same size typically have a factor of 10 difference in how long they lead. So they’re doing something really right and sure enough, it turns out to be that they have evolved away to make fewer of these byproduct I mentioned these things called free radicals, when they breathe per unit oxygen consumption, how they do it is still very much unclear. What how we could exploit and piggyback on what they do is even more unclear. So yeah, long stories. There are definitely things we would love to understand better about how certain species level on time. We shouldn’t get our hopes up too much with regard to how to use that information to live longer ourselves. The might be a few isolated examples where we do find out information that is medically relevant but in learned if you

Will Jarvis 23:07
got it and I love that anecdote about the the possums on island to the Outer Banks. It’s a really good reminder that there are pathways and mammals that could be switched on and, and extend lifespan, like it is very possible in some sense, which is, which is really cool to hear. And that natural environment as well. All right, are there any therapies currently available, you know, caloric restriction Metformin, anything that you’ve found that would be a good idea to start thinking about now.

Unknown Speaker 23:39
So these are, first of all, these are definitely not things that I would have. Because they are being studied by other people. But also the reason why they’re not being studied by me and by my by my people, by my team and by this community, is because they are up, only to give us a very small amount of additional healthy life. Now, God, I’m certainly not saying that they’re useless, not at all. I first of all, I believe that even a very small amount of additional healthy life is well worth having. And of course, the thing about calorie restriction ad these drugs that trick the body into thinking it’s in a calorie restricted state when it isn’t like rapamycin, or Metformin or resveratrol, you know, these things they already exist. Other things that we’re working on that don’t already exist. So that’s great. But yeah, I don’t work on those things. Because I’m in the real McCoy, I’m interested in actually getting to stuff that can truly eliminate damage from the body, essentially carrier restriction and, and likewise, all these drugs, what they do is they slow down somewhat, the rate at which the body generates more damage, they don’t get rid of pre existing damage. So inevitably, that obviously means that they have a Reflect, especially on people who only start the procedure or the medicine when they’re older. But more than that, it’s really important thing to understand is that long lived species like humans get far, far less benefit from calorie restriction than shortly speaking like mice or rats. And this is actually, again, something that is not surprising. It’s an immediate prediction of evolutionary theory. I don’t need to go through the details, really. But it’s essentially revolved around the fact that long famines don’t happen very often, short famines happen often enough for evolution to pay attention to them. Long famines don’t. So you ended up getting a much lesser effect in long lived species, but not a zero effect, or at least we we presume, if not there. So um, yeah, absolutely. But I don’t work on it myself. Gotcha.

Will Jarvis 25:55
That makes sense. If someone wants to help, you know, and I did this is very personal to each person. But But what what are some of the some good things you would suggest some reading materials, you suggest? If someone’s wants to get involved with aging? You know, is it donating? Is it you know, working on research directly? And again, this is all like, dependent on each person’s skill set? Well, what are some good ways to help? Right?

Unknown Speaker 26:19
Well, so yes, I mean, of course, you’ve really kind of answered the question yourself, you just, it depends on you, it depends on your skill set depends on your circumstances. So absolutely, you know, the wealthier you are, the more difference you can make. I do, however, want to emphasize very strongly that every dollar counts. So you know, the more we can build up our grassroots funding, the better plenty of sensible proportion of Americans from small donations, they do not think you can’t make a difference, just because you’re not wealthy. Second thing is, of course, advocacy. And this is something I always like to point out when I’m only slightly tongue in cheek here. But the poorer you are, the more people you know, who are wealthier than you. grassroots advocacy going out and actually talking to your friends and your family and your colleagues, and saying, Listen, this is the world’s most important Crusade, get with the, you know, get with it, understand that this is coming, and the sooner it comes to the bathroom, and the more support they have, the better. Or for that matter, even the less opposition they have, the better because a lot of this is just getting into people’s heads that this is not a thin, you know, that yeah, that they should not be opposing this, we have, I will tell you, this is a fact we have at least three people who are close friends, and who have never given us a penny, even though they really, really are interested and supportive of all this verbally. Why? Because their spouses won’t let them. So yeah, I mean, so getting going opponents to be less vigorous opponent is just as important as getting support to be more vigorous supporters. And then, of course, there’s the wider advocacy that’s doing the kind of thing that you’re doing right now, you know, getting the word AI podcast or any kind of other kind of media, right? It doesn’t have to be made that your interviewer used to have to be me because I was the only person out there. Because it’s not that way anymore. We are one of the other enormous piece of the progress that has happened over the past few years, is that other people have come along who are, you know, sophisticated enough and knowledgeable enough to be giving the right answers to all the questions, but they don’t parrot me, they say in their own words, and they say in their own style. You know, I think I’m pretty damn good at what I do. I’d love you want to be by now cuz I’ve been doing it long enough, but I only do what I do. And there are certain audiences with whom my message resonates. And there are other audiences with whom it doesn’t, because I’m not speaking in the kind of language that they like to hear. So, you know, I still remember the first time I saw this parish up on stage, she got into this field starting in 2013, when she came to win a conference on the conference, well organized, and she learned the field pretty fast. And she started getting out there on stage and on camera. And, you know, she’s the kind of person who can, who can pull heartstrings in a way that I will not be able to do if I live to 1000 She is unbelievable. I was in tears. And you know, it’s not the she’s not the only one by any means, but actually actually springs to mind away because it was so it was a movie for me. But yeah, I mean people like so Keith cometo in a great person. He runs something called leaf, the life extension advocacy foundation based in New York. And he’s fantastic on stage and on camera. And so now, you know, we’ve got this thing that I would always praying for this diversity of methods. And the more we have, the better.

Will Jarvis 30:10
That’s excellent. That’s really excellent. Well, all right, I really want to thank you just, you know, you could have done a lot of things with your life, you could have gone into investment banking and made, I’m sure a lot more money than you do. Working on aging, you know, all kinds of everything’s we chose to work on a problem that, you know, no one else thought was really important. And I think that’s a at the time, and I think that’s a really valuable thing. And I’m really excited to see where the field goes in the next 10 2030 years.

Unknown Speaker 30:37
Well, I will very much hope that you won’t have to think that long. 15 years, the drug will be more or less done. That’s the plan. That’s excellent.

Will Jarvis 30:48
All right. Well, Aubrey, where can people find you? Where should we send people? If they want to, you know, find your work?

Unknown Speaker 30:53
Really? Yes. The best place to go sense.org our website? I might be in the show notes. But yeah, so September 8, and November. So it’s September dot o RG. It is written for everybody, you know, we have material, they have absolute experts all the way through to complete novices. And of course, lots of news about what we’re doing what other people are doing, you know, the usual kind of stuff where I’m speaking. And you know, the contact form questions you have, then please, you know, just write to us that we are very well behaved about answering those. And of course, there’s a nice, big friendly Donate button. Awesome.

Will Jarvis 31:31
Well, thank you so much for coming on today. I really appreciate it. It’s my pleasure. Well, thank you for having me. Well, that’s our show for today. I’m Jarvis and I’m will join us next week for more narratives.

Transcribed by https://otter.ai

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