Why We Get Old & How We Can Stop It - Dr Andrew Steele | Modern Wisdom Podcast 265

Andrew Steele is a scientist, writer and presenter. Ageing is a phenomenon we're all familiar with and is completely taken for granted as a fact of reality, but do we have to accept Expect to learn why curing ageing might be easier than curing cancer and all other diseases, the unfortunate truth of fasting for longevity, why the next decade will be the most exciting for lifespan research and much more... Sponsors: Get 35% discount on everything I use from The Protein Works at https://www.theproteinworks.com/modernwisdom/ (use code MODERN35) Get 20% discount on Reebok’s entire range including the amazing Nano X at https://geni.us/modernwisdom (use code MW20) Extra Stuff: Buy Ageless - https://amzn.to/38Ya1aF Follow Andrew on Twitter - https://twitter.com/statto Get my free Ultimate Life Hacks List to 10x your daily productivity → https://chriswillx.com/lifehacks/ To support me on Patreon (thank you): https://www.patreon.com/modernwisdom #ageing #longevity #biohacking - Listen to all episodes online. Search "Modern Wisdom" on any Podcast App or click here: iTunes: https://apple.co/2MNqIgw Spotify: https://spoti.fi/2LSimPn Stitcher: https://www.stitcher.com/podcast/modern-wisdom - Get in touch in the comments below or head to... Instagram: https://www.instagram.com/chriswillx Twitter: https://www.twitter.com/chriswillx Email: [email protected]

Speaker names marked ? are inferred from speaking time and the show’s known hosts — they are not voice-verified.

• 0:00Speaker 00

  Toward the end of the book, I start talking about what a cure for aging is actually going to look like. I think it's going to be much more complicated than anything we've talked about so far. The reason I've got some faith that it's going to happen is because we're undergoing a computational revolution in biology at the moment. You know, even if we don't get to general intelligence, I think we're going to get to a point where AI programs are able to interpret this huge sort of torrent of data that biologists are producing in a way that humans just can't understand.

• 0:25Chris Williamson?

  What is aging?

• 0:28Speaker 00

  That is an excellent question. There are many, many different ways you could define this. And I think every different scientist will give you a different answer. But I've got two ways of thinking about it, one of them statistical, one of them biological. And the statistical way of thinking about it, which I think is the most sort of catchall definition of aging, is it's what happens to your risk of death with time. So the longer you've been alive, how much does your risk of death increase? So to take the example of humans, if you're in your 30s, your risk of death is about one in a thousand per year. If you're lucky enough to make it as far as 80, your risk of death goes up to 5% a year. So it's, you know, hundreds of times more. And what, yes, so what that means, actually, if you look at the stats is, can I start that again? Because I think it's not hundreds of times, is it? The difference between five and a thousand is 200, it's 200 times more, I'm right.

• 1:13Chris Williamson?

  That's fine, it's correct, it's correct, Andrew. The internet, you're here because you're a scientist, not because you're a mathematician.

• 1:21Speaker 00

  And what you find actually is that the better people are at maths, in terms of like the proper theoretical hardcore maths, the worse they are at mental maths. And you find yourself second guessing yourself all the time. If you get a proper hardcore number theorist, they can't add two and five.

• 1:34Chris Williamson?

  I remember my old housemate did a PhD in pure mathematics. And he once ordered a four seater taxi for five of us because apparently in pure maths, you count from zero.

• 1:45Speaker 00

  Yeah, yeah, it's off by one error, classic in computer programming as well.

• 1:48Chris Williamson?

  Unbelievable, man, you spend all this time doing maths, you can't count to five?

• 1:52Speaker 00

  I know, got a PhD, can't even manage it. So what, yeah, yeah, so humans, the sort of way to sum up all that stuff that I just failed to add up in my head is that our risk of death doubles every eight years. So you can say in some sense, our rate of aging is encapsulated in this number. We're saying that, you know, it's called the mortality rate doubling time. So how long does it take your mortality rate to double? And if you look around the animal kingdom, this isn't universal at all. For mice, it's a matter of months. But if you look at something like a giant tortoise, which you'll find on the cover of my book. And the reason is that they're what's called negligibly senescent. They have a risk of death which is constant with time. So effectively, their mortality rate doubling time is infinite. And that doesn't mean they're immortal. It doesn't mean they're going to live forever.

• 2:33Speaker 00

  But what it does mean is it doesn't matter how long ago they were born, their risk of death stays the same. So that's the statistical definition of death. The biological definition, sorry, of aging. The biological definition of aging, I'd say, is to look at the individual components of the aging process. And there was a paper published in 2013 called The Hallmarks of Aging, and it lists these nine different changes in your cells and your molecules. And they they tend to increase with age, all of these things. They tend to, if you accelerate these changes, then the animals will have their aging accelerators, they'll die more quickly. And if you slow these changes down, then the animals get less disease and die more slowly.

• 3:09Speaker 00

  So that's the sort of criteria by which they define these different hallmarks, which are a sort of more nitty gritty molecular, what's actually going on definition of aging, as opposed to that high level statistical one we started with.

• 3:19Chris Williamson?

  Yeah. Is there a cultural blind spot around aging? Like, hearing the word cure and aging in the same sentence is not very common.

• 3:30Speaker 00

  Yeah, I think there is. And I've I've used the word cure slightly to the chagrin of some of the scientists who read the book, actually. Because it is a bit of a controversial way of putting it. But the reason I want to put it that way isn't necessarily because I think a cure is just around the corner. But it's because I want to normalize the idea that aging is something that should be cured. I think there's an interesting discussion as to whether it's, you know, should be classified as a disease or not. But nonetheless, whatever it is, whether you think of it as a disease or whether you just think of it as a sort of a disease syndrome, I've heard scientists describe it as, or if you just think of it as a natural process. The fact is, it means that we get much more likely to get diseases, we get much frailer, we lose our mental faculties. None of those things are good things. And I think to try to cure them, to at least aim for that target, is where we should be going with medicine.

• 4:12Chris Williamson?

  Are there not things we need to sort out first, like cancer and heart disease? Surely they're Easier to fix and quicker to happen than than aging.

• 4:22Speaker 00

  Yeah, the strange, the strange thing is, it might actually be easier to saw aging than to saw all of those diseases individually. So the reason that our risk of death doubles every eight years as it does. You've got to die of something, right? You don't just like drop dead in the street with no underlying cause. And the things that you die of are actually exactly the diseases you just listed, cancer, heart disease, stroke, dementia. All of these terrible diseases which are primarily suffered from by old people, you know, a few people in their 30s do get diagnosed with cancer. But by and large, it's people in their 60s and their 70s and their 80s. And the risk of all of these diseases rises in exactly the same sort of terrifying exponential way with time. And that's because it's all the same biological processes. They drive wrinkles, they drive grey hair, so the sort of superficial changes.

• 5:03Speaker 00

  They drive the, you know, loss of muscle mass that makes it harder to do stuff around the house, the frailty. But they also drive the cancer, the heart disease, the dementia, et cetera. And actually, if you look at the, the international classification of diseases, it's this massive sort of attempt by scientists and doctors to assign a code to everything that can go wrong with your body. And there are about, I think there are 11,000 of these in the latest edition, I might have got that slightly wrong. It's, you know, it's thousands and thousands of different ways that you can go wrong. It's a bit depressing when you think of it like that. But a significant fraction of these are basically aging. You know, they're, they're things that are, they're cancer, there's loads, you know, every single subtype of every cancer in every organ. There's all the different ways that your heart or your circulation can go wrong. There's everything that can happen in your brain, all the different kinds of dementia. So we can either, as scientists and doctors, go after these thousands of individual causes.

• 5:49Speaker 00

  Or we can go after the root cause, the thing that causes almost all of those diseases. And that's aging. And so although, you know, aging's not going to be an easy thing to crack, it's going to be, you know, there's some research still needed. It's quite possibly going to be easier than taking out every single one of those possible ways your body can go wrong all at the same time.

• 6:05Chris Williamson?

  Yeah, you said much of modern medicine targets symptoms a few steps removed from the root cause of the illness. Guess it relates to what you're talking about there.

• 6:14Speaker 00

  Exactly, yeah. And I think that our, it's sort of natural because the way we used to treat infectious diseases, you'd get, you know, you'd get measles. And what you need to do is either vaccinate people so they don't get the, so they can fight off the virus before it becomes an infection. Or you need to treat them in some way. And if it's a bacterial infection, you can give them antibiotics. And once you've got rid of the disease from the body, you've cured it. But with something like cancer, you can, even if we had a cure for cancer, right, we could remove the cancer from the body, perhaps very successfully. But then it would still, in essence, be an old body that you are left with, a body with a huge risk of developing another cancer, a body with a huge risk of heart disease, perhaps already has heart disease, perhaps already has the beginnings of dementia. And so by treating the diseases, these sort of atoms, these individual entities that are separate from the processes going on the rest of the body, it's just an approach that's doomed to failure ultimately.

• 6:59Chris Williamson?

  Yeah. I was interested to look at the average life expectancy work that you'd done. And I think it was 35 years old, about 20,000, 30,000 years ago, classic hunter gatherer. And only 200 years ago, the average life expectancy was 40 in the UK, which that blew me away. But you highlight an interesting quirk, I guess, of statistical science, that that is skewed massively by infant mortality, that you've got ridiculous volumes. I think it was like, you only had a 60% chance of making it to 18, 20,000 years ago, something like that?

• 7:36Speaker 00

  Yeah, so it's hard to get the exact numbers, but that's the sort of ballpark. Yeah, it's basically like tossing a coin to see if you'll make your 21st birthday or something like that. Which is ridiculous to modernise. Like, imagine if we were running that sort of gauntlet in our childhood and teens. It's crazy.

• 7:48Chris Williamson?

  Yeah. Yeah, that was mad. So one question that I became fascinated by, and I've had David Sinclair and Andrew Scott talking about longevity on the show before, and I didn't even think to ask them this question. Is there a purpose to dying? I thought that we were supposed to be adaptive fitness maximisers, right? And surely this certain end to life is a bit of an error. Like, why has evolution not made us immortal?

• 8:15Speaker 00

  Yeah, it's an interesting question. And there's, so there are two aspects to this. Firstly, is there an adaptive advantage to dying? And secondly, is there an adaptive advantage to aging? Which is sort of, they, they sound like they're the same question, but they're not. So to answer the first one about death, there could be an argument that the reason that creatures die is because evolution, it can only happen between generations, right? You and I, we've got our DNA, that was, you know, half from my mum, half from my dad. And that DNA is what we're stuck with for life, you know, more or less. We can't, you know, adapt to be better, faster, stronger. We can obviously, we can train, we can eat well, we can do whatever we like to try and improve our fitness. But ultimately, we're stuck with the genes that we've got. So if you want to evolve, you've got to have kids. And those kids will differ from you in a few different ways, you know, different, the partner you had the children with.

• 8:58Speaker 00

  And it's through these tiny differences, maybe that'll give your kid a slight evolutionary advantage over the kids of the people next door. And over generations and generations, whatever, you know, properties your child had that made them fitter in for that environment, will cause them to evolve. So the problem is, if you have an organism that doesn't die, how does it evolve? Because it can't, unless it can, you know, go in and change its own DNA, which isn't a thing that organisms can do.

• 9:20Chris Williamson?

  The changes in DNA occurred due to birth, not death. Dying doesn't seem to be a part of reproduction.

• 9:27Speaker 00

  No, it's not. But imagine, so imagine that we're, you know, cheetahs out on the savannah. And we're really well adapted for our particular evolutionary niche. We're really good at running fast. And then, and we're also immortal cheetahs. So this is a, this is a, you know,

• 9:40Chris Williamson?

  I love it already.

• 9:40Speaker 00

  Experiment, shall we say? So we're immortal cheetahs running around on the savannah, you know, eating gazelles. The problem is, you know, say, for example, there's a, there's a massive famine of the particular kind of tree that the gazelles we most like to eat, eat. And so all the gazelles die and we eat the ones, you know, we eat the handful that are still left. Suddenly, what we need to do is adapt. Our environment's dramatically changed. We haven't got any gazelles to eat anymore. But because we have got our fixed DNA, we can't adapt. We've still got sharp teeth, we're still, you know, adapted to run quickly and catch stuff. We're still adapted to digest meat. And the only way that we could adapt would be to do that over evolutionary time. So perhaps our kids are slightly better at eating leaves than we were. And so they can slowly move away and perhaps get an omnivorous diet. So they can eat meat and leaves and eventually they might become completely vegetarian. Or, you know, this is,

• 10:25Speaker 00

  A slightly ridiculous thought experiment, but the point being, once you're in existence, if you just don't die, you can't adapt to your changing environment. And so it's it's actually a point of contention how important a fact this is. But it's definitely possible that a literally immortal species just couldn't evolve. And so as soon as the world, you know, the world would change around it, and it would be doomed that way.

• 10:45Chris Williamson?

  Yeah, I've been fascinated. I went to Dubai earlier this year, and I went to the marina and saw a huge crocodile, sorry, an alligator that they'd taken from God knows where. And I was reading about how alligators and sharks basically looked out with their adaptive properties, and they're essentially unchanged for millions and millions and millions of years. They just landed perfectly on their evolutionary niche, as you called it. And I guess that that would be the only way that you'd be able to survive. That the roll of the dice would be like, 20 sixes in a row. You're like, yes, I got the teeth I needed, and the hide I needed, and the legs I needed, and everything. And also, this environment better not change.

• 11:30Speaker 00

  Yeah, exactly. And as soon as, you know, we could imagine something like climate change could certainly push certain sharks out of existence, just because they've been adapted for this environment for millions and millions of years. But if we come along and change it too quickly, or an external factor comes along and changes it, they might not be adapted anymore. And so, yeah, that could be the end of those living fossils.

• 11:46Chris Williamson?

  What's the other half of why we die then, in terms of evolution?

• 11:51Speaker 00

  So in terms of evolution, aging is an accident. And so you're absolutely right to sort of couch it in terms of, evolution is designed to maximize fitness. And that isn't always quite in the way that you expect. In that, it doesn't always mean that you're going to be bigger, faster, stronger. Because obviously, you know, otherwise, animals would slowly evolve to become huge monsters, and they clearly don't do that, right? They optimize themselves to for their current environment. And so that might mean occasionally, it makes a change that doesn't seem like it's making the animal fitter. Like, for example, again, if we're back to our cheetahs, not immortal anymore, but we're back to our cheetahs on the savannah, there is probably a point at which there's no point running any faster. Because what that means is that you're going to spend energy building bigger muscles and stronger bones in order to be able to run more quickly. But if you can already run faster

• 12:35Speaker 00

  than all your prey, you're effectively wasting that energy. And you could be using that energy for something else evolutionarily. So you could be using it to, you know, make your fur slightly better camouflaged, or you could be using it to have more kids. And so all of these things are ways to redirect your energy away from sort of the naive conception of what fitness means. Because I think, as you know, we often imagine fitness to be big, hard, strong animals. But that's not always the case. You know, we've got frogs, we've got insects, we've got all things that are tiny and, you know, strong and weak and all different kinds of animals adapted very differently for different environments. So aging is exactly the same sort of thing. And it's, it's an evolutionary compromise because if you build an animal that's effectively immortal, so it doesn't, you know, has a risk of death, doesn't change with time, for example.

• 13:15Speaker 00

  It's got to put energy into being immortal. It's got to put energy into maintaining its body. It's got to put energy into making sure that no cancers start off. And it's got to have an immune system that's constantly patrolling, looking out for those cancers. And all of these different sort of ways to spend that energy, it could be spent in other ways. You could spend it having an extra kid, or you could spend it having slightly stronger muscles to catch up with those gazelles. So there's this sort of, as, as an organism, you're trying to choose between, you're trying to optimize across all these different parts of your body. And that could be longevity, that could be how strong your muscles are, that could be how tall you are, depending on the environment you're in. And longevity isn't always going to be the winner. So even though you might expect the biggest, you know, biggest, fastest, strongest, longest lived animal to always win. Sometimes the short-lived one's going to win because it puts less energy into maintaining its body.

• 14:00Speaker 00

  And it can put more energy into something that's more evolutionarily important in its niche.

• 14:03Chris Williamson?

  It's like a Malthusian trap a little bit. It's like, um, that you're going to be outcompeted by something else that has a more, a, a higher chance of not only surviving, but also reproducing. And if your survival is at the, uh, cost of your reproduction, like it's not happening.

• 14:24Speaker 00

  Yeah, that's exactly right. And I think this, this phrase, survival of the fittest, it's really become like a part of popular culture. But actually, what we should say about evolution is it's reproduction of the fittest. And that's the key point.

• 14:35Chris Williamson?

  Yeah, because it doesn't matter if you survive. You can survive, but if you don't reproduce, any traits you have have been competed out of the gene pool.

• 14:43Speaker 00

  Exactly. And like, at some point, a, a bus or a, you know, or a cheater is going to come along and get you and you're gone. You might as well not have existed.

• 14:50Chris Williamson?

  I'll tell you what I found out this year that I thought was fascinating. It's the, uh, non-zero existential risk from natural risks that we have. That means we have to have technological progress. So this is from, uh, Toby Oates, The Precipice. And there's a lot of concerns at the moment around, are we moving too quickly towards artificial general intelligence or bioweapons or nanotechnology? And we're all going to get turned into gray sludge or paper clips or whatever the next thought experiment is. But. What he did say is there is a non-zero chance that we're going to be killed. Eventually, if you stuck around for long enough, we're going to be hit by an asteroid, or a supervolcano is going to go off, or the sun's going to swallow us, or something. So we need technological progress. And it's kind of the same as we're seeing in evolution, right?

• 15:34Chris Williamson?

  That's just like a macro aggregated version. You need to have this cost payoff between the two.

• 15:40Speaker 00

  Yeah, definitely. And I think that's, that's exactly right because there are some problems that we can't evolve our way out of. Like if we had just not, if we hadn't developed computers and spacecraft and all these different things, like what on earth are we going to do in a billion years when the sun starts getting a bit bigger and hotter? And the earth just gets toasted and all the oceans boil. Like, there's no level of natural living evolution that's going to get us out of that situation. So fingers crossed that we can sort it out ourselves.

• 16:03Chris Williamson?

  So why do we age?

• 16:06Speaker 00

  Fundamentally, that's exactly why. It's this trade, this evolutionary trade off. And what that, what that means is that our bodies in a variety of ways have decided not to put as much energy into maintaining our physique as they could as we get older. And so the idea is that, you know, if I were to put all that energy into maintaining my body, I would have fewer kids. You might have more kids because you put less energy into maintaining your body from an evolutionary perspective. And your two kids are eventually going to mean that they have four kids and they have eight kids. Whereas my one kid's only going to have two kids. It's constantly going to be a step behind. And that means that in an environment where, you know, eventually I'm going to get hit by a bus or I'm going to get eaten by a saber tooth cat or, you know, just going to die of an infection in prehistory. Then your weight of numbers is going to outweigh my slight extra lifespan advantage. And ultimately, evolution makes this trade off.

• 16:51Speaker 00

  And unfortunately, it's come down with us aging.

• 16:54Chris Williamson?

  What's the process of us aging? What, what, what is happening inside? Why does it, why does it do what it does?

• 17:01Speaker 00

  It's a variety of different things. It is basically a load of things falling out of balance, a load of things getting broken. And it's, it's, it's, it's quite a complicated thing, right? So I think there's, there's, there's, there have been a lot of theories of aging that have tried to ascribe it to a single cause. But I think what the hallmarks show us, and I talk about the hallmarks in my book in a slightly modified form. They've got nine, I've got 10, I sort of, I combined a couple and added an extra couple. But it's basically the same kind of thing because obviously the process is, is very similar. But it's everything from the DNA inside our cells getting damaged to the populations of cells falling out of kilter, to certain molecules being damaged and never being repaired, to signals that change that cause cells' behaviour to change. So it's a complicated

• 17:42Speaker 00

  sort of processes upon processes upon processes, which ultimately mean that the environment inside our body is very different by the time we're 60 or 70 or 80 than it is when we're 20 or 30. And that is what causes us to age fundamentally.

• 17:55Chris Williamson?

  It's bizarre, isn't it? Because I think we're not conscious of the fact that our cells are constantly replacing themselves. I think is it every seven years? You don't have a cell left in your body that was there seven years ago, is that right?

• 18:08Speaker 00

  So it depends on the tissue. It's really interesting because like, so our guts are literally turning over every few days.

• 18:14Chris Williamson?

  Okay.

• 18:14Speaker 00

  And our red blood cells in our blood, they last about three or four months. But then if you look in other parts of the body, bones, I think probably are on about the seven or 10 year mark. But if you look at some neurons in the brain and some heart cells, you are literally born with them and die with them. So they last your entire life. And it's actually really fascinating why these different organs have chosen these different sort of levels of turnover. Because obviously, in an environment like your guts, it's rough and tumbling there. You're getting lots of toxins in your food, you've got bacteria, you've got your microbiome, you've got all sorts of stuff going on. And clearly, evolution has decided the optimal way to deal with that is to constantly replace those cells. Whereas in your brain, it's all protected. There's something called the blood-brain barrier that keeps almost everything out of your brain that isn't needed. And that

• 18:56Speaker 00

  means that a neuron is in a really quite a safe environment. And so apart from a few special cases, like the olfactory neurons, the neurons that are responsible for your sense of smell, they turn over really rapidly because they're exposed to the outside environment, basically. They're exposed to all kinds of dangers. Whereas a neuron that's like deep somewhere inside your skull is so well protected that evolution, for whatever reason, has decided it's better to leave that neuron completely intact and never change it for your whole life.

• 19:20Chris Williamson?

  That's fascinating. I thought I've seen something probably on Instagram that was like, every seven years or so, all of your cells turn over. But now, everybody that's listening has it in the tank to say, actually, there's some neurons are in the blood-brain barrier. And I think you'll find they're exactly the same. So did your research uncover any animals that live for ridiculous periods of time? Obviously, we know our life expectancy at the moment. What about other animals?

• 19:51Speaker 00

  I think the craziest in terms of actual lifespan tend to be a little bit further from humans. So the longest-lived vertebrate, which means animals with a backbone, is actually a kind of shark called the Greenland shark. And it's hard to be exactly sure of their age because it's not as though we've like tagged a shark 400 years ago and then like watched it until it died. But they think from various sort of chemical analysis that the oldest Greenland shark ever found was about 400 years old. So that's crazy. But then as you move a bit further away from us in the in the sort of tree of evolution, and a tree was an appropriate choice of word, actually, because we think the longest-lived single organism on the planet is a tree called a bristlecone pine. It's in the White Mountains in California. It's a top secret location because they don't want vandals to go and chop down this like incredible piece of Earth history.

• 20:31Chris Williamson?

  It's a secret tree. Shit the bed.

• 20:34Speaker 00

  Yeah, a secret tree. And it's they think it's about 4,850 years old. They took a core out of it and they counted the rings, just as you know, tree rings, just as you'd expect. And it was, I think it was about 4,800 in the 1950s. And so sort of moving that forward, that tree was a sapling before the pyramids. Like, that's just absolutely mind blowing to me. That that tree has basically seen the whole arc of human civilization from atop this sort of windy, arid mountaintop in California.

• 21:03Chris Williamson?

  That's unreal. What about this hydra thing?

• 21:07Speaker 00

  Hydra, fascinating. That's another example I was going to suggest, actually. And that's another one where we don't actually know how long they live. But we can extrapolate from how long how long we've watched like loads of them live to how how many would still be alive after a really long time. So Hydra, they're these tiny freshwater creatures. They're incredibly simple. So they've basically got a mouth at one end and a bum at the other and not a great deal else going on. And the thing that really captured scientists' attention about them initially was that you can chop any bit off a hydra and it will turn into a new hydra. So you can chop it in half, you'll get two hydra. You can chop it into four, you'll get four hydra. And so it has this incredible, you know, if you if you think salamanders are good at regenerating, it's got nothing on a hydra. You know, you can't chop a salamander's leg off. They'll get a new leg, but the leg won't go into

• 21:47Speaker 00

  a new salamander. So they've got this incredible power of regeneration. And as scientists started watching them more in the lab, they realized they're actually living a surprisingly long time as well. And that it's been extrapolated. Again, we obviously haven't done the actual full length experiment, but 10% of Hydra would still be living after 1,000 years if the death rates we've observed so far are accurate.

• 22:10Speaker 00

  Which is just bonkers because we sort of imagine the bigger and more complicated and more human like an organism is, the longer it's going to live, like in general, as a rule of thumb. But these are literally like microscopic organisms and they can live a thousand years.

• 22:23Chris Williamson?

  Is this like tardy grades as well? They're pretty hardcore, aren't they?

• 22:27Speaker 00

  They are pretty hardcore. I actually don't know if we've got any good longevity data on tardy grades. I've not seen it. They're certainly hardcore in the sense that they can like survive ridiculous environment hazards, insane levels of radiation, vacuum, horrible chemicals. And they just basically, I think they just dehydrate themselves and turn themselves into this like super hardcore remnant tardy grade. As soon as you just add water, you get the tardy grade back again.

• 22:50Chris Williamson?

  Yeah, it is like those sea monkeys that you used to get as a kid.

• 22:53Speaker 00

  Yeah.

• 22:54Chris Williamson?

  You said that the effect of fasting is one of the most universal in all of biology. What's that mean?

• 23:02Speaker 00

  So we've observed, the first proof that we had that aging could be changed in animals was some experiments that were, they were sort of kicking off a bit around the early 20th century. But the first proper formal experiment on this was done in the 1930s by a guy called Clive Mackay. He was looking at rat development and he was really fascinated by if you feed rats different amounts of food, but you give them, make sure they get the right amount of nutrients, but you feed them different numbers of calories, what does that do primarily actually to their development? Because back in those days, people weren't living quite so long. I think there was more of a focus on the beginning of life, optimal nutrition when you're growing up, sort of stuff. But what they noticed was in these experiments, that the rats that were given substantially less food, and we're not talking like a diet here, we're talking like half the amount of food that the other

• 23:43Speaker 00

  rats were being given. They just kept living. So they were, they lived about 40, no, hang on, they lived about 80% longer, the rats. And not only did they live longer, they lived longer in good health. So these rats that were dying almost twice as late as the rats that were eating a normal diet. When they did an autopsy after those rats were dead, they basically looked the same. They looked indistinguishable from the rats that had died, you know, 600 days previously, a couple of years previously. And what that suggests is that this process was slowing the aging process down. By eating less, you slow down aging. And we've since discovered this works in all kinds of different organisms, ranging from yeast, so the stuff that used to make beer, all the way up through flies and mice

• 24:24Speaker 00

  and dogs and bizarre creatures that live in pond water. And the only question mark really is to what extent it works in humans. And we've got some experiments in monkeys that show that it certainly makes them live healthier, but it doesn't seem to make them live longer. So it's this really fascinating universal effect. But one of the things I found most infuriating reading about this, because I was thinking, can I do this? And on the one hand, I almost certainly can't because I just like food too much, to be really honest. I've tried doing a bit of fasting. I just get very, very hungry. I get very grumpy. It's not a good look. But the second thing is that it's hard to motivate yourself to do something so difficult when the evidence is so mixed for humans. And we just don't know whether you're going to be putting yourself that. So there's this sort of joke in the

• 25:09Speaker 00

  biogerontology community. Fasting doesn't actually make you live longer, but it certainly feels like longer. And so you don't want to, you don't want to get yourself in a position where you're putting yourself through absolute hell, feeling hungry literally all the time. And then, you know, you get to the age of 80, drop dead exactly on cue. And the scientists announce, oh, you know, we've done the study now. We've worked out the dietary restriction works in every other organism apart from us.

• 25:32Chris Williamson?

  Where's your money on this? If you had to put a bet on?

• 25:38Speaker 00

  I think it's probably going to turn out that it improves health, but doesn't do that much on lifespan. I'm not going to say it wouldn't give you a year or two, but it's not going to. Because I think the best evidence for this, quite aside from any like complicated studies, because there have been attempts to do this properly, proper medical research type randomized trials where you give some people, you know, reduce some people's diets and leave other people eating normally and see what the difference is. But quite apart from these sort of, you know, proper high octane studies. The fact is, you look around the world, there are people in different religions, people in different cultures. We've got such a variety of diets globally. And the fact is, there's nobody living to 150. So what that probably suggests is that there's nothing we can really do to our diets or our lifestyles within reason that's going to have a dramatic effect on our lifespan.

• 26:24Chris Williamson?

  It would be, I mean, for the longevity, R slash longevity on Reddit. If, if it's true that fasting doesn't do anything, there are a lot of people, I mean, they've spent half the amount of money on food that they would have done, but they've

• 26:37Speaker 00

  It's that bonus, yeah.

• 26:38Chris Williamson?

  Potentially been twice as hungry. So yeah, it is a, it is a big trade off.

• 26:44Chris Williamson?

  Just going back to that rat rat study, there was calorie restriction and fasting are two different things. You can eat half the amount of food just as frequently, or you can eat less food or a similar amount of food less frequently or more frequently. How, what are the effects that were seen from that?

• 27:05Speaker 00

  So, this is, this is so naughty. And I think there's a real problem, actually, with the animal experiments. So mice is the one that they've, they've done a bit more experimentation in now. They're the more common lab animal. And there's, there've been, you know, scientists trying to distinguish the effects between dietary restriction, so eating less all the time, and intermittent fasting. And that, again, this can come in a huge load of forms. Like, do you eat every other day? Do you do the five-two diet and eat five days a week and take two non-consecutive days off? Do you go for a week without food every few months? Like, there's just a huge spectrum. There's even this 16/8 time-restricted feeding idea, where you only eat during an eight-hour window during the day. So there's just this huge range of different things to test. And I think there's a worry in the, in the science community that actually the mouse experiments haven't tested any of these things very reliably.

• 27:51Speaker 00

  The reason being, mice are nocturnal, and PhD students are not nocturnal. So, the way that the PhD students tend to feed the mice, is they'll go in at the end of their, you know, at the end of the workday, give them their ration, so half their food if they're on dietary restriction, or their, you know, whatever they want if they're eating what they like. And then they'll come back the next morning and the food will be gone. And if you actually watch the mice that are doing that, the mice that are on dietary restriction, they're starving. So they run in, they eat all their food in one go, and then they don't eat for 23 hours. So effectively, they're doing sort of this weird combination of dietary restriction and intermittent fasting. And it astonished me, I was chatting to a scientist about this, and they were saying, actually, you know, so this is obviously, we've, we've recognised this problem. And just now, like, literally in the last few years, they've

• 28:34Speaker 00

  started doing some experiments, I don't think any have yet been published, with automated feeders, like you get for your, your dog or your cat if you're away from home. And it, it just, I just, it's head slapping, like, how have they only thought? It's not as though this is 2010 technology. You know, we've had automated pet feeders for decades, haven't we? And yet, for the first time, you know, there's been enough interest in sort of distinguishing the differences between DR and IF to actually do the experiment properly and find out.

• 28:57Chris Williamson?

  We only put wheels on luggage about 30 years ago. So if that's, if that's a stat to remind us just how shit we are at innovation sometimes, then that's all we need. So how can we treat aging? We've said it's a big problem. We've said that downstream risks from it are essentially endless. It is the, how would you say? It is the axis of so much suffering in life, right? Like, if you live for long enough, all of the people that you care about, all of the people who care about you are going to die and it's going to be incredibly traumatic. So obviously, holding that off or stopping it entirely would be a universal good. How can we treat it? Where do we start?

• 29:36Speaker 00

  I think the way to start is to look at the hallmarks of aging and to look at ways to slow and reverse those. And my favourite example, because it's the one that's furthest forward and it's quite an intuitive one, is looking at senescent cells, which you might have heard of before. So these cells, they were first discovered in the 60s and they were discovered by a guy called Leonard Hayflick. And he was doing, these are very sort of cells in a dish experiments. They're very far removed from actual, you know, organisms and humans. He was just growing these cells in a dish. What he noticed was they'd divide and divide and divide, what cells do. And then after about 50 divisions, they'd just stop. And not only did they stop dividing, they looked weird under the microscope. They started out as these quite sort of ordered looking things. But if you look at a senescent cell, even, you know, a non-expert can see it, it's this sort of weird, blurry, splayed out, you know, it looks radically different from a non-senescent cell.

• 30:22Speaker 00

  And as a result, because these cells seem to be old in the sense they divided a lot of times, and because they looked weird, and because they stopped dividing, they were christened senescent. And senescent is just a scientific term for aging, basically. So it's aged cells. And these were of interest and people wondered, you know, that set the train of thought in motion. Could it be that the aging of our bodies is driven by the aging of the cells inside them? Could it be that cells inside us have divided too many times when we get to the age of 60 or 70 or 80? And that's one of the drivers of the aging process. And so this was sort of observed for the next few decades. But I think the real excitement about this started in 2011. When for the first time, some scientists got, at the Mayo Clinic in the US, got some mice that have been genetically modified, and they've been genetically modified such that

• 31:05Speaker 00

  they had an extra gene. And what that gene did was, it meant if they were given a drug, which is otherwise pretty, you know, it's innocuous, it's something that if you and me took, nothing would happen because we haven't got this special gene. But if you do have this special gene in your cells, then the gene basically goes, am I in a senescent cell? If I am, I'm going to kill it. So it's sort of a suicide switch, but just for senescent cells. And so the mice took this drug, activated the gene, and the senescent cells in their bodies committed suicide. And what they found was that this made the mice healthier. Actually, it didn't make them live longer, because this first experiment was done in a special, they had another genetic modification that made them age really quickly, and so they all die after six months, basically. So that, that wasn't the big result. The big result was that it made them healthier. And so then subsequent

• 31:48Speaker 00

  experiments started doing this in normal mice that didn't have this premature aging condition. And what they found was, they can make them live longer, they can make them live healthier, they get cancer later, they get cataracts later, they, they have better fur, which is obviously crucially important to all of us. They are, you know, they're more cognitively, they, they age cognitively more slowly. So if you get one of these mice and put it into a maze, a young mouse will be very curious and go exploring, whereas an old mouse will be a bit more nervous and probably not going, you know, run around, never look to see what's going on. But an old mouse that's been given these senolytic drugs, drugs that kill senescent cells, is much more like a young mouse. It's more curious, it's looking around. And so it seems, from what we know so far, that removing these cells globally reverses the aging process. And the idea would be then,

• 32:31Speaker 00

  that this is one hallmark of aging. If we can go after the rest of them, then we can start to slow and reverse aging in a multitude of different ways. And altogether, that should slow our aging down, basically, overall.

• 32:41Chris Williamson?

  I'm going to guess that just getting the old out isn't sufficient. There must be something new that needs to be put in to replace that. How does that, how does that sort of fit in?

• 32:50Speaker 00

  So in the case of the senescent cells, it'll be interesting to see if this pans out, like in every part of your body, because there might be some places where, exactly as you say, getting rid of the old thing doesn't, isn't sufficient. So for example, you're just saying that neurons, you have your neurons your whole life. If you were to kill your senescent neurons, then that's really bad news, right? You're going to start losing brain very rapidly and there's nothing to replenish it. However, if you kill the senescent cells in your skin or your guts or your blood, none of these are really a problem because they're constantly refreshing. Then other cells are just going to divide, take their place. And so, you know, they're going to very, very rapidly replenish those senescent cells that have been killed. So it really depends on the part of the body. And yes, we probably will have to replace cells in some of those places.

• 33:32Speaker 00

  But what's surprising is it's almost how lucky we've got with these first round of senolytic treatments in that they're imperfect, they don't kill all the senescent cells. And we are just naively killing cells. And yet it seems to make the mice live longer, live younger. I don't think this is going to, this is going to be the end of senolytics. I think we're going to have to refine them. But we have struck surprisingly lucky, at least in mice, with these first treatments.

• 33:55Chris Williamson?

  What about stem cells?

• 33:58Speaker 00

  Yeah, we're definitely going to need more of those. I think, um, yeah, so that they're a particular example where if you were to, you know, say a large number of your stem cells became senescent and you killed them, then you might end up with a problem because you'd end up with what's called stem cell exhaustion. And, um, so what we're going to have to do there is stem cell therapy effectively. We're going to have to go into the body and replace those stem cells with new fresh versions that are able to keep your tissues, you know, turning over at the rate they should be turning over.

• 34:25Chris Williamson?

  It's going to be a increasingly complex system to continue to move. What about like ongoing repair running? Is there anything we can do there?

• 34:36Speaker 00

  Yeah, and I mean, the thing is, this, this applies just across all the hallmarks of aging. And it depends how you choose to tackle each one of them. So with the senescent cells, I think probably that getting rid of them is the most promising approach. But it might be that repairing them is another option. And there are various ways that you can go about repairing them as well. So, um, one thing that you can do, for example, you've probably heard of the epigenetic clock. I think you've chatted with David Sinclair about that. And, um, the sorts of, uh, treatment that he works on. Where you insert these genes and it reverses the epigenetic clock can reverse cellular senescence as well. And it'll be interesting to see whether or not that's a wise move because often senescent cells have gone senescent for a reason. The reason they've stopped dividing is because they are at risk of turning cancerous or because they're badly damaged or broken in some other way. But

• 35:19Speaker 00

  it might be that rather than killing every single senescent cell, there are some that we want to rescue, or there are some that we want to replenish. And I think it's really going to vary on a case by case basis. Exactly like you say, it's complicated. It's not going to be as simple as taking a single pill that slows or reverses your aging. It's going to be a question of managing all these different effects, perhaps in different ways and different parts of the body, in order to make sure that we can maintain young bodies overall.

• 35:41Chris Williamson?

  Rather than adding a gene on, is there a way to upgrade genes wholesale?

• 35:47Speaker 00

  Yeah, so gene therapy is coming on. It's not quite at the point where we can, you know, inject a new gene into every cell of your body yet. That's a real challenge. But certainly, the dream is that you can, you'll be able to turn genes off, turn genes on, put new genes in, put new copies of genes in. And all of these things are certainly possible in the lab, and they're becoming more possible in humans. So I was really excited last week as we record this, I saw a story about the first gene therapy for something called sickle cell anemia, which is a condition that's particularly common in people of African descent. And the reason for that is that it's, it creates a sort of distorted form of hemoglobin, which is the protein that carries the oxygen in your blood. And what that form of hemoglobin does is it creates sickle shaped, so sort of shaped

• 36:29Speaker 00

  like a sickle as in a hammer and sickle, so letter C shaped cells. And they're very, they're not very good at catching oxygen, carrying oxygen because they've got a much smaller volume than a normal round blood cell. And they also tend to get jammed up in really small blood vessels, so the tiny capillaries, they can jam it up and stop the blood flow entirely, which can cause incredible amounts of pain for people who have two copies of this gene. Because if all their cells are sickle cells, they're not getting the proper amount of oxygen to their tissues. Sometimes it gets jammed up entirely. It's a really, really terrible disease. The reason it's endemic in Africa is because having one copy of this gene is actually quite good news if you're in a population that is historically affected by malaria, because these sickle cells can effectively jam up the mosquitoes. Bite, probostis, I think is the word, I'm not entirely sure, I'm not an insect biologist.

• 37:14Speaker 00

  But you know, so it jams up the mosquitoes and they're unable to take a drink of blood from you and they're unable to infect you with the malaria parasite. So that's why this evolved. But now in the modern world, it's becoming less and less important. And in fact, as I say, if you have two of these genes, it's very bad for you. Anyway, long story short, the scientists have come up with a way of extracting the stem cells from your bone marrow, which is the place that your blood cells are regenerated. They then reactivate a gene for something called fetal hemoglobin. So we have a different kind of hemoglobin that works when we're inside our mother's wombs. And they reactivate that gene, which is normally deactivated in adults. And then reinsert those blood cells. And not only that, like in the intervening time, they get rid of all the other blood cells, all the other blood stem cells with chemotherapy. So at the moment, it's not a hugely pleasant procedure. But then they inject these new cells back in with this gene reactivated.

• 37:59Speaker 00

  They're able to produce blood cells that are normal again. So they lose these symptoms of the sickle cell anemia. And it works, it's just been, I think it's the first successful trial. I'm not sure it's been approved yet, but it's just, that's just so exciting. It's an example of a lot of the kinds of technologies that I talk about in my book. Like, you know, removing cells, modifying them outside the body, doing gene therapy, putting them back in. It's not at the stage where we can, you know, enact all of the ideas that I talk about in the book. But it's certainly a serious step along the way to having actual gene therapy, actual cell therapy in the clinic.

• 38:30Chris Williamson?

  Will the cure for aging arrive in time for me and you?

• 38:36Speaker 00

  I think it could do. I don't want to make any guarantees, but I think what I, what I find most remarkable about this, and I, toward the end of the book, I start talking about what a cure for aging is actually going to look like. And I think it's going to be much more complicated than anything we've talked about so far. It's going to be more complicated than addressing those 10 hallmarks of aging. The reason I've got some faith that it's going to happen is because we're undergoing a computational revolution in biology at the moment. You talked about AI earlier. You know, even if we don't get to general intelligence, I think we're going to get to a point where AI programs are able to interpret this huge sort of torrent of data that biologists are producing. In a way that humans just can't understand. And to give another exciting thing that's happened in the last couple of weeks, DeepMind, this company that are part of Google, announced that

• 39:18Speaker 00

  they've managed to get AI to fold proteins, to work out how biological molecules fold up in our bodies, which has been a problem that we've been struggling with for decades. And suddenly they've come in and they haven't solved it, I wouldn't quite say, but they've made significant strides. And the fact they've done it in just a few years suggests there are significant more strides to come if they can keep on squeezing those performance gains out of the AI. And we're just going to get to a point where you've got so much data, we can sequence genomes, we can sequence, you know, we can look at proteins, and we can combine all that together in a computer. And as I was writing this, I was thinking, wow, this just sounds like total sci fi. We're going to need a, you know, a huge model, a computer model that understands the whole of the workings of the human body, all of our DNA, all of our proteins. We've got, you know, like 40 trillion cells in our body all working together. You're going to have to model every single one of those. And, you

• 40:03Speaker 00

  know, I just thought this is crazy. We're not going to, the cure for aging is never going to arrive in time. But actually, you know, if you think that that kind of idea is a bit pie in the sky, it's 50 years away. Imagine I'm in my 30s now. I'm, you know, fully expecting, even if nothing happens in medicine, I should still be alive in my 80s. And that means that even if you think that technology is 50 years away, it could be in time for a lot of people who are alive today. And actually, the way that you can get more optimistic about this is because by the time we're 80, we're going to have senolytic drugs that are able to kill us in essence cells. In fact, we're not just going to have the first generation we have now, we're going to have much improved versions of those things. We'll probably have a few of the other hallmarks sort of ticked off the list at the same time. And that's going to mean that we live longer and healthier lives. And I don't want to put a figure on it, but let's imagine that you live an extra

• 40:47Speaker 00

  five years as a result of all that stuff, and five years in good health. That means, you know, when we get to the age of 80, we might be biologically 75 or 70. So we're a bit more able to take whatever these new treatments are. And, you know, we might be alive in time to take them, basically. So I don't think, you know, I don't want to guarantee at all. We've just got no idea. It could be that this stuff's completely impossible. And although it seems like we've got an idea now, we might get 10 years down the line, think, oh, Jesus, you know, we just, we completely underestimated hallmark number four, we're screwed. But even if you think that some of these developments are 50 years away, they could be in time to matter for a hell of a lot of people who are alive today.

• 41:22Chris Williamson?

  It's like biology or longevity's got a hard problem and that how or how would you say, you know, the great filter hypothesis about why the Fermi paradox exists, why there's no aliens out there. There could be that and we may have got past it or we may be able to get to it, or it may not exist. Yeah, it'll be a fascinating area of research, presumably as well.

• 41:42Speaker 00

  It's a really weird time to be alive because we're at a point in history where I don't, you know, we're not a thousand years away from curing aging. I don't think, you know, if I wanted to be really conservative, I think in the year 2000, people's risk of death is not going to depend on how long ago they were born.

• 41:58Chris Williamson?

  Year 3000.

• 41:59Speaker 00

  So the in the year 3000, like that definitely there's, and I'm saying that to be like so thoroughly uncontroversial, but the question is, is it going to be 50 years? Is it going to be 100 years? Is it going to be 200 years? I think that's an open question. And because, you know, say, say we reach the age of 200 through whatever breakthroughs happen. It just seems remarkably unlikely to me that we won't have made such huge strides in biology and computation that we can effectively expect to live longer still. So I'm not saying we will make it to 200, but if we do, the possibility of us living much, much longer is just wide open, I think.

• 42:31Chris Williamson?

  Presumably for everyone who's listening to this, the longer that we all live, the better our chance at being alive longer if a cure is found.

• 42:42Speaker 00

  Exactly. And even if, even if we don't get as far as a cure, like every year you live in good health additionally, there are going to be new breakthroughs in medicine. It might not even be breakthroughs in aging. It might be a new cancer treatment or a new heart disease treatment. And I think as some, a lot of people, like there's, there's a real risk of starting to talk about immortality and that kind of thing. And certainly a lot of journalists, a lot of podcast hosts are very keen to talk about like really, really long lifespans and stuff that's sort of on the edge of our ability to predict at this point in time, quite frankly. However, if you look back in history, this is, this is really uncontroversial because people who were born in the 1930s, a lot of those people survived because vaccinations are starting to come online. You know, if they, if they got an infectious disease when they were 20, there would have been just

• 43:25Speaker 00

  the first few inklings of antibiotics. And that meant that when they were 70 in the year 2000, there are a load of heart treatments that were completely unimaginable in the 1930s. Like talking of, you know, we didn't put wheels on suitcases until the seventies. We didn't invent chest compressions until the 1950s or 1960s. And they certainly weren't like widespread use until the late 60s. I was stunned when I found that out researching the book. Because you just think it's the most obvious thing in the world. If your heart, which beats, stops beating, why don't you physically beat it for it effectively? And yet, it took us thousands of years as a species to come to that realisation. And so if you were, and what that means, I've got quite sidetracked, but what that means is that if you were alive in the year 2000, because of medical developments that happened in the 1930s, 40s and 50s,

• 44:10Speaker 00

  you were then able to benefit from a whole load of new medical technology that simply didn't exist at the time of your birth. And I think, you know, whether or not we're going to live to 1000 or 10,000 or 102, the fact is, every year you stay alive longer is another opportunity for some medical breakthrough to happen that could benefit you.

• 44:26Chris Williamson?

  Let's say I want to live as long as I can. What do I do? I want the full Monty.

• 44:33Speaker 00

  I think at the moment, a lot of it is just follow the basic health advice. You know, make sure you don't get too fat, make sure you get a bit of exercise. Because what you find when you drill down, you know, don't smoke, you get down, you drill down into what all these different bits of health advice mean. And this is something that actually really fascinated me. There's a chapter in the book about health advice. And what's really fascinating to me is that it's all of the things that are best for your health, all of the things that you've been told that you should do by your doctor or your dentist or whatever, effectively slow down the aging process. So smoking, effectively, obviously it hits your lungs the worst. It puts you at massively increased risk of lung cancer. It puts you at massively increased risk of other lung diseases as well. But it also accelerates the aging process globally.

• 45:16Speaker 00

  It increases this process called inflammation, which we know drives the aging process. It makes non-lung cancers more likely as well. It increases your risk of heart disease. So effectively what a smoker does, if you, you know, smoke 20 a day, you're basically 10 years older. Your biological age is 10 years higher than your chronological ages. And so you suffer from all those diseases of aging that much sooner. And it's the same with all of this health advice, like making sure you eat well, making sure you exercise, is effectively slowing down the aging process. And, you know, there's five or 10 years to be gained by doing this stuff. But what I think is the most important thing, and it's easy to overlook because I think, you know, all of us are really. I'm fascinated by diet, reading, we're talking about dietary restriction earlier. I was, I got obsessed when I was writing that bit of the book, being like, what is the optimum diet?

• 45:57Speaker 00

  You know, if I just read enough papers, it must be out there, it must be in the literature somewhere, you know? And what I came away thinking actually was, we're going to have cured aging before we know exactly what the optimal diet is. Because there are just so many variables, there's protein, there's carbs, there's fats, there's all the different vitamins and nutrients. There's when you eat them, there's how much of it you eat when, there's what you eat on which days. The number of variables is just astronomical. And so what I think is the single best bit of health advice, which doesn't sound like health advice, it sounds a bit weird. But it's to campaign for more research into aging. So wherever we are in the world, write to your representative, write to your MP, talk to your friends and family. I know this sounds like I'm promoting my book, but get them to read my book.

• 46:37Speaker 00

  The reason being, the more people who understand that treating aging is a thing that we can do and that we should be aiming to do. We're going to get a critical mass, we need voters to know this, we need politicians to know this. And that means they can give money to the scientists who are working on this stuff. And then you get to a point where what's determining the length of your life isn't exactly whether you eat the right combination of fruits and veg on the right day of the week. It is the progress in biology, it's the process in aging biology, sorry, the progress in aging biology effectively. And I ultimately think that's going to make a far bigger difference than any of the lifestyle interventions that we could talk about.

• 47:10Chris Williamson?

  What about exercise? What's the most optimal form of exercise that you found?

• 47:16Speaker 00

  And again, that's so tricky. I think something that I, I certainly personally neglected was strength training. So as you get older, your muscle mass and your muscle strength decreases. And it starts off relatively benign, but from your mid 30s onwards, it starts to decrease. And when you get into your 60s and 70s, it really starts to fall off a cliff. But what's surprising is that actually, that is to a significant extent optional. Which means that if you engage in strength training, you can ward off frailty in your muscles for a substantial amount of time. I even found one study where they gave some non-agenarians, so people in their 90s, strength training. And they were able to walk faster, they were able to lift heavier weights. You know, it's not like they were going down to the gym and powerlifting or anything like that.

• 47:58Speaker 00

  But they, you know, their quality of life was substantially improved by this strength training intervention. And so it's never too late to start. And also, yeah, just, just make sure that you look after your muscles, because they are one of the things that's going to really impact on your quality of life.

• 48:10Chris Williamson?

  Going back to the diet thing, and especially the intermittent fasting point that we came up with earlier. Do you think there's a bit of a Pascal's wager going on here? It's like, I don't know if if it's going to work, but it's probably not not going to work. So I might as well do it.

• 48:28Speaker 00

  Yeah, and that's the that's the really frustrating thing about it, isn't it? It's like infuriating. Because I would I would go with that if it was easy to stick to. But the problem is, in addition to the fact it might work and you might as well give it a go. It is exhaustingly, you know, being that hungry is just so tiring all of the time. And it's not like there are no disadvantages at all. So in the, um. I think the best studies actually are of dietary restriction rather than intermittent fasting, which is just because intermittent fasting stuff is that little bit newer. And so the human trials aren't quite there. You know, if you ask me again in two years, I suspect we'll have a bit more to go on.

• 49:04Speaker 00

  But what they found in dietary restriction trials is that people sometimes lose a bit of bone mass. So they had a few people have to like drop out of the trial because they were losing bone mass. They had someone drop out of the trial because they were getting anaemic, which means they didn't have enough red blood cells. And the other thing it can do is reduce immunity. So, you know, there's no point living effectively indefinitely if you're then just going to get the flu and die anyway. Or coronavirus these days, of course. So that it's not, unfortunately, it doesn't come quite come down to Pascal's wager. Because firstly, it's just tiring and really dull. And secondly, there are these sort of these nasty disadvantages that mean it's just not a no brainer to try it.

• 49:42Chris Williamson?

  Hmm. It seems to me that those are exceptions rather than common issues. Certainly after speaking to David Sinclair a couple of years ago in Harvard. I was like, I was so eating the drinking the Kool-Aid, the calorie free Kool-Aid of intermittent fasting. And you're right, I know some buddies who find it really easy. Michaela Peterson, who's a good friend of mine, she consistently does like four day fasts or seven day fasts and stuff. Which is just, yeah, that's another another level. But

• 50:19Speaker 00

  It really is.

• 50:20Chris Williamson?

  I don't know, man. I don't know. I was, you've thrown a spanner in the works. I was I was all team team calorie restriction now and I the story's not as simple as

• 50:30Speaker 00

  Something that happened to me in exactly this way. So calorie restriction is really hard. Intermittent fasting is still quite hard. And trying to not eat for a full day is really difficult. But the sixteen eight thing, I thought that sounds quite doable. So actually, my wife and I decided to try that at the beginning of, I think it was, I can't remember if it was last month or the month before. And literally, the week we started doing it, and it's quite doable, by the way, you know, just not having, you just skip breakfast, start eating at twelve, then make sure you get your food in before eight PM. It's, I was a bit hungry in the mornings, but I often used to skip breakfast, you know, as a, as a young, young adult, back when I was irresponsible. So that's, it's just not that hard to do. But then, literally that week, a study comes out saying, we've done a proper randomized trial of this. Admittedly, it's not necessarily applicable

• 51:13Speaker 00

  to everybody, because they looked at only white people, they looked at people who are slightly overweight to see if it would reduce their weight. And what they found was basically it didn't do anything. The people who are in the control group and the people who are in the experimental group doing the sixteen eight, they both had about the same trajectory of their weight, their inflammatory markers in their blood were about the same, their cholesterol was all about the same. And, you know, that's not nails in the coffin, but the scientists who, who did the experiments, he said, I was taken in by sixteen eight fasting, I was completely convinced by it. But now we've done this experiment, I'm stopping today.

• 51:41Chris Williamson?

  You are pissing on everyone's party today, Andrew.

• 51:45Speaker 00

  It's really, it's really annoying. It's not like, and I don't want to. I mean, it's, it's really frustrating. I feel like, I don't know what we can do about it, because I don't think we're going to have the evidence that tells us one way or the other. And that means, I think there are, there are some really compelling arguments made by people who are like, D R advocates. That, you know, so, so for example, this study in rhesus monkeys, there were two studies done. One of them was done at a university of Wisconsin, and one of them was done at the National Institutes for Aging. And one of them found that the monkeys lived longer, and one of them found that they didn't. They both found the monkeys lived healthier, by the way. So let's, you know, park that. We can, we can still potentially look forward to healthier lives, but let's talk about longevity now.

• 52:29Speaker 00

  There are, there's enough in, there's enough differences between those studies to like have DR advocates and skeptics arguing until the end of time.

• 52:36Chris Williamson?

  What's DR?

• 52:37Speaker 00

  Because, oh dietary restriction, sorry. The reason I'm pedantically calling it dietary restriction rather than calorie restriction is that recent work has suggested it might be proteins or amino acids, which is the important thing to restrict. So it just shows you, there's just, this is so complicated, right? It's, it's, it sounds like alluringly simple when you hear rats ate half as much, they lived almost twice as long, boom. But actually, like, what is it about their diet that changed and what exact way that conferred those particular benefits? And that's how you end up in this mess. And these, this monkey experiment is, or these pair of monkey experiments is a really great example of that. Because, so the NIA monkeys, they were fed a relatively, uncontrolled is unfair, but they're, they're fed a natural diet of like fish and grain and various bits and bobs,

• 53:21Speaker 00

  which by its nature is uncontrolled. Because obviously you can't like create a fish that has a particular combination of nutrients inside it every single time. And the monkeys in the University of Wisconsin version were eating these sort of sciency purified pellets. So they had, you know, fat and protein and sugar in exactly predetermined amounts. And the University of Wisconsin monkeys, the ones who are on the control group, who are allowed to eat what they like, were literally allowed to gorge on as many of these fatty sugary pellets as they wanted. And you can sort of see where I'm going here. These monkeys were on like their fast food McDonald's, soft drinks diet. They had fatty sugary pellets, all you can eat, stuffing them in. And that meant that the dietary restriction group, who are on a restricted number of these pellets, was healthier and lived longer.

• 54:02Speaker 00

  However, in the NIA study, where they were given this slightly more diverse but slightly less scientifically precise diet, what it turned out was the dietary restricted monkeys were healthier for longer, but they didn't live any longer. And so the simplest explanation of this, perhaps, is, simplest and perhaps simplistic explanation, I should say, is that there's a sort of sliding scale. So if you're eating hamburgers and fries and soft drinks all the time, like the Wisconsin monkeys gorging on these, these little pellets, then you can benefit from restricting your diet a bit. If you're already eating not too much of an unhealthy diet, or a reasonable amount of a basically healthy diet, there's not much benefit to going further. That is one interpretation. However, if you're a dietary restriction proponent,

• 54:45Speaker 00

  for whom I've got a lot of time, then you go, okay, well, actually, there are other problems with the NIA study too. One of them is their monkeys were from a much more diverse background and they are a much wider range of ages. So they started some of these monkeys on their dietary restriction when they were in, you know, late adulthood. And they also had monkeys from all different parts of the world. And this, if there is an effect, this could potentially obscure it because they found that dietary restriction works differently in different, in different strains of mouse, for example. And so you can imagine that an Indian macaque and an African macaque might have a slightly different response to it. And so all of this just muddies the waters. And it means you can make quite a convincing argument that actually, if we were to go back and do these experiments properly, we would find an effect. But what it makes me think is that there might be an effect. I don't want to like completely rain on everyone's parade.

• 55:30Speaker 00

  But if there is an effect, it's clearly not a doubling of lifespan like we see in rats. Because these are two groups of scientists who did these experiments. They were trying in good faith to replicate these ideas. And they had slightly different approaches granted and there are various things you can quibble about. But if this doubled lifespan, we'd know about it, right? One of them might be a bit less than the other one, but we'd see it, we'd see the results in the experiments. But given that the results are a bit equivocal, you know, maybe at the absolute most optimistic end, you might get five or 10 more years. But if you're already eating a basically healthy diet, I think it's hard to expect that you're going to like dramatically alter your lifespan through DR.

• 56:04Chris Williamson?

  What's unique about us? Every animal, the most comprehensive, reliable effect in biology is calorie restriction or dietary restriction to extend lifespan. And then at some point in our, like, couple of recent histories worth of evolutionary change, someone just put a bit of computer code bug in.

• 56:25Speaker 00

  Turn that off.

• 56:26Chris Williamson?

  Yeah, now we're wrecked. What's different?

• 56:28Speaker 00

  Yeah, it's rubbish, isn't it? The, the, the way to sort of reassure yourself a little bit is part of the reason is probably that we are, we're incredibly long-lived for our size.

• 56:37Chris Williamson?

  We're pushing the limits of that already.

• 56:40Speaker 00

  Exactly. And there was even a theory that I think has now been debunked. But that maybe humans have already turned on a lot of the mechanisms that underlie DR in order to reach our extended lifespans that we have. They've actually gone back and had a look at that and it isn't true. It's the right sort of way of thinking about it. Because, um. So firstly, I think these results are much more variable than are sometimes suggested. And I noticed this when I was doing some research for the book, because there's, I'll tell you the simple story, then I'll tell you why it doesn't quite work. The simple story is that the reason that animals have this response to reduced food intake is imagine you're a mouse, you've got a maximum lifespan of a couple of years. You might only have a lifespan of one year because you've got predators and you've got disease and that sort of stuff. So you've got a very, very short lifespan.

• 57:22Speaker 00

  Imagine there's a famine, so there's a season where for some reason there's not enough food. There are two things you can do in that season. You can either have a last ditch attempt at having some kids before you starve to death, or you can hunker down, you can engage your dietary restriction response, and you can slow your aging in order that you'll live that little bit longer, so you can survive until the next season when food's hopefully plentiful again and have some kids. And there's a serious advantage to that second approach. And that is that your kids will then be born into an environment where there isn't a famine going on. So rather than just having them immediately in an act of desperation. So the theory goes, and it's not entirely supported, and there are D R proponents who will fight back against this, but the idea is that if you're a short-lived animal, it's really important to have a very flexible lifespan with respect to how much food you're eating.

• 58:06Speaker 00

  Because if you're going through a famine, you need to survive much longer, a significant fraction of your lifespan in order to get to a point where you can have kids and it be useful. However, if you're a human, and even in prehistory, as you rightly said, you know, because of a lot of infant mortality, our life expectancy was 35, but actually if you made it out of childhood, or you made it past 15, then you could expect to probably live into your 40s or 50s. And that means if you have a famine for one year, like, it's not ideal, but it's not a significant fraction of your reproductive lifespan. And so you'd expect that as organisms get longer-lived, they might get less of a response to dietary restriction as well. And what you also find when you look at the data, which makes it more confusing, is that

• 58:48Speaker 00

  this, this sort of tight correlation between lifespan and size and the tight correlation between lifespan and dietary restriction response doesn't really hold very clearly. So dogs, for example, which we've also tried dietary restriction in, has, it has a surprisingly small effect, and I don't think anyone really knows why. And actually, there are lots of animals that have a really big response and a really small response, and it's not quite as neat as it seems at first glance. Even though it is incredibly universal, the size of the response can vary very significantly.

• 59:15Chris Williamson?

  I love that theory. It makes complete sense and I'm a big advocate for evolutionary biology and evolutionary psychology. So I'm seduced by that. It's plausible, but everything today's come with a caveat. There's not a single thing that's been definitive, except for a couple of studies. And even the studies, well, this could have been different and that could have been different.

• 59:36Speaker 00

  Yeah, yeah, yeah.

• 59:37Chris Williamson?

  So, yeah, it's strange that something that's, like I say, the prime vector of so much suffering and a universal, a ubiquity across all of our lives is also something that we're incredibly ignorant and all of the waters are still very muddy about. Oh, that's something, actually. What about supplements and drugs? NMN, NAD, resveratrol, metformin, baby aspirin, the David Sinclair stack?

• 1:00:01Speaker 00

  I think we haven't got enough evidence to go for those. I personally don't take any of them. I think that the evidence could get there in the next few years, but we need to see human trials. There have been a few experiments in mice that David's done that have shown some effect. I don't think they've shown longevity on any of those things.

• 1:00:17Chris Williamson?

  It's like regrowing optic nerves and mad shit like that, isn't it?

• 1:00:21Speaker 00

  But yeah, crucially, that was with gene therapy rather than with a drug. I'm actually, I'm much, much more excited by the epigenetic reprogramming stuff than I am by things like NMN. Because I feel like the epigenetic reprogramming seems to be going in and fixing something about our biology. And it's not to say that NMN has no effect. It's something that declines with age and it is clearly, you know, something that is potentially going to improve health and lifespan. But I just don't think we have the evidence yet. That's not, again to say, it doesn't work. This is me being extremely pedantic scientist. But we just need to wait until we see human trials in order to be absolutely sure. My feeling with all of these things is that if you're a young person today, especially, you can afford to hold off. Because we're going to know the answer to a lot of these questions in the next five or 10 years. And your aging at the moment is relatively under

• 1:01:06Speaker 00

  control, right? You know, you're, you're young, everything's basically fine health-wise. The fascinating question to me is like, what would I do if I was 65 or 70? And then I'd really be scratching my head.

• 1:01:17Chris Williamson?

  Take everything. Take, take absolutely everything. Don't eat. Take all the drugs.

• 1:01:24Speaker 00

  It does turn into much more of a Pascal's wager at that point. Because, so the, I think the one that I'm

• 1:01:31Speaker 00

  Most excited is the wrong word, but like the thing that we're going to know about in the in the nearest term that might be beneficial is metformin, which is this diabetes drug that looks as though it might slow down aging. And there's a massive trial that's going to start in the US shortly. I think it's been delayed because of COVID, but it's going to be looking at whether if you give healthy sixty somethings this metformin drug, will it slow down the rate at which they get cancer and heart disease and various other things? Because there's been some suggestive evidence that it's normally, as I said, given to diabetics. And there's been some suggestive evidence that shows that these diabetics who are taking the drug can actually live longer than non diabetics. And the thing about non diabetics is they tend to be, you know, they tend to be less overweight, they tend to be a bit fitter, they tend to be healthier, they tend to have less other diseases.

• 1:02:13Speaker 00

  And yet, even still, the diabetics on metformin in a couple of studies have marginally outlived them, which suggests that maybe if you gave the metformin to a healthy person, they'd live even longer still. But that's again, something we're just going to know the answer to in five years' time. This trial should be done by then. And so if you're a young person, there's not really any incentive to start knocking back the metformin. But if I was 65, I mean, there definitely are people out there on the internet who go to their doctor and ask for them to prescribe the metformin, even though they're not a diabetic. And I wouldn't want to advocate that, but I can certainly see why it's, you know, why it's a temptation at that point.

• 1:02:45Chris Williamson?

  One of the things that fascinated me, especially after my episodes with David Sinclair, is how passionate the longevity community is on the internet. There's very few episodes that I've ever put out that have evoked such a visceral emotional response. And I became really interested in it. And as we released more clips through 2018 and into 2019, I became increasingly interested because each time a clip went up, there were people who were, even about things that weren't to do with the episodes, the camera angle, or whether or not I touched the microphone, there were people who were really, really, obviously just on edge and agitated generally about this topic, really, really annoyed about

• 1:03:28Chris Williamson?

  the fact that I hadn't digged into the precise microgrammage of this particular drug that David was taking, or whatever it might be. Do you think that longevity is another, or the longevity movement is kind of another denial of death? Is it a replacement for religion in people fearing what happens next? Are they pinning their hopes onto science now as the new god?

• 1:03:52Speaker 00

  It's a good question. I think it's, there's, there's obviously a huge spectrum from, I, I mean, as you, as you can see, as you said earlier, like I caveat everything. I'm, I'm a hundred percent like extremely cautious scientist, or at least I try as hard as I can to be. But there are definitely people who take these early results and run with them. And it's a, it is a fascinating bit of psychology because I'm not motivated by death per se. I think I got interested in this stuff because I, I realised that there, there is this underlying biology that gives rise to all these different diseases. And fundamentally, you might have heard the statistic that aging is responsible for about two thirds of deaths globally. And that fraction is only increasing as the global population ages. And it's, it's that sort of thing that

• 1:04:36Speaker 00

  fundamentally got me into it. So I, I find it hard to like peer into the psychology of someone who, I mean, death, death can be scary. It's, it's a bizarre thing to think about ceasing to exist. And I think this philosophical idea that, you know, you won't know, it doesn't matter because you won't be there. I still, you know, don't like, don't particularly enjoy peering into the abyss. And it's not something I'm looking forward to. And I find it very strange, like the converse attitude. I've got a lot of sympathy for people who don't want to die. But there are quite a lot of people who like push back and say, why are you working on aging? You know, isn't death what gives life meaning and that sort of thing? And I just find that side of things completely baffling. Because I think there's, there's almost nothing where if you were pursuing some goal that was going to reduce the amount of death in the world, that

• 1:05:20Speaker 00

  anyone would criticise it. Like, I, I think a world in which is exactly the same as today in every respect, but there's a bit less death, is probably a better world. Like, I don't think that's me being a zany mad, like immortalist scientist saying that. And yet, there are some people who really push back in the other direction as well. So I think there's a, it's a complicated relationship we've got with this thing that's been a fact of life, like for as long as there has been life. It's not even like humanity this is spanning over. It's literally the whole of the existence of biology, there has been death. And so I just think, yeah, it's, it's really fascinating that we're now at a point in history where, you know, we're not sowing monkey testicles to people to try and make them live longer. We're not like giving them weird combinations of herbs and that, yeah, in the 1920s, there was a big movement around trying to work out whether-

• 1:06:05Chris Williamson?

  Sowing monkey testicles?

• 1:06:06Speaker 00

  Oh, yeah.

• 1:06:06Chris Williamson?

  Where?

• 1:06:09Speaker 00

  I'm actually not a hundred percent. It was quite hard to get the details.

• 1:06:11Chris Williamson?

  It wasn't a straight swap, was it?

• 1:06:14Speaker 00

  I don't, I don't think so. No, because I mean, the thing is, you probably want to keep your own, wouldn't you? Because they're useful.

• 1:06:19Chris Williamson?

  A monkey's, a monkey, a monkey testicles, the ones that are huge. They are, aren't they?

• 1:06:24Speaker 00

  Do you know what? I'm actually not sure what the logic was at all behind this idea.

• 1:06:28Chris Williamson?

  Anyone who knows anything about monkey testicles, please leave it in the comments below.

• 1:06:32Speaker 00

  Yeah, please, please, please write in. I'd love to get lots of correspondence.

• 1:06:35Chris Williamson?

  Have you considered philosophically what would happen to the way that we view our lives and the meaning that's associated with them? If we were to make a significant leap in terms of lifespan, if we're talking, we go from an average of 80 to 160 or to 200. What do you think that that would sort of mean for us?

• 1:06:56Speaker 00

  Do you know what? I don't think it would make much difference. And that sounds like a strange answer, but I think, because, and this, this sort of goes back to the death gives life meaning idea. Like when you go for a job interview, or when you ask someone on a date, or when you, you know, do basically anything in your life. It's very rare for you to be doing that because you know that you're going to die in 50 years' time. I don't think that acts as a motivator. And I live my life like, not, not wanting to sound like some kind of hedonist. I just live it day to day. Like mostly, I get up in the morning, I look at my calendar, I see what I've got to do. I've got a bit of an idea of what's coming up in the next month. You might plan a holiday three months in advance. You might plan a house move a bit further in advance than that. I'm saving for my pension. But like, ultimately, I'm not giving my day to day life at the age of 60, a very great deal of thought.

• 1:07:42Speaker 00

  And so I think if I was going to live to 160 or 560, I just, I, I think I'd probably continue living day to day and week to week. Like it would change some things about the way that I, the way that we function in society. But I think ultimately I'd still, you know, go on holiday, try and have new experiences. I can't think it would make that massive an amount of difference to how we live.

• 1:08:02Chris Williamson?

  One thing.

• 1:08:03Speaker 00

  I don't think people plan for the long term that much now.

• 1:08:05Chris Williamson?

  That's a, that's a very, very correct observation. And I suppose that's adaptive as well. If you don't know how long you've got left to live, it's pointless having this unbelievable long-term planning module slotted into the back of your brain. Yeah, one, one thing that I'd considered was, um.

• 1:08:23Chris Williamson?

  How we might fear accidents much more because the cost of an accident, I'm 32. Let's say I get hit by a bus tomorrow. If I'm unlucky with my normal lifespan, I've got about 50%, sort of 40 or 50% of the way there.

• 1:08:39Speaker 00

  Yeah, not bad.

• 1:08:40Chris Williamson?

  Yeah, you know, that's all right. Like, I've got a bit, but if your lifespan is 200 or 500 years, the prospect of an accident, I wonder whether downstream from that culturally, societally, we would be so much more protective over exposing ourselves to pathogens and viruses, over doing scary things, because the weight of how much you have to lose is so much greater.

• 1:09:09Speaker 00

  Yeah, definitely. And that makes me quite optimistic, actually. That is one way in which I think things would change for the positive socially. Because another example is war. Like, the reason that we consider war an acceptable thing, to the extent that we do, is because, like you say, if you were to go into war, even as a 20-year-old, you haven't lost, you know, 200, 300 years of future life. Whereas if we start having casualties in wars, and that's the sort of scale of the tragedy, not to take anything away from the tragedy of dying in battle now, but I really think it would surely cause us at that point to sit down and think, what on earth are we doing?

• 1:09:43Chris Williamson?

  Transhumanism and artificial intelligence uploading our minds to the Skynet and getting Arnold Schwarzenegger down versus beating aging to get us to live over 200 years. Which one do you think comes first?

• 1:10:00Speaker 00

  I hope we do it biologically. And the reason is actually quite philosophical. I say I hope we do it biologically unless the philosophy can be sorted out to my satisfaction. Because my concern is... With mind uploading, firstly, it's just weird. Like, I quite like being a squishy biological body. I think, you know, maybe this is the evolutionary psychology speaking, and I've got used to like living in this weird floppy, whatever the hell it is that we live in. But I'm quite comfortable with that. I don't particularly want to be uploaded in a computer. The second sort of deeper philosophical issue with it is, imagine you did copy my every neuron into some computer program. And then that computer program, you know, you could have done that interview with the computer program. Instead, it would have given you all the same damn answers, or at least ones that were indistinguishable in terms of cognition.

• 1:10:44Speaker 00

  But is that computer program actually me? And I think when, if you're scared of dying, and I think, so what I think is morally significant about death is that I think we should avoid terminating consciousnesses. Because conscious beings, they've got plans, they've got dreams. You don't want to, you know, cut that off and mean that they can no longer have any freedom, any plans, any dreams, et cetera. So that's something you want to avoid doing. And if you were to upload someone into a computer and then maybe discard their biological brain, because you don't need it anymore. You've got absolutely no guarantee that consciousness has continued. And philosophers have got some ideas of how to get around this, which is, for example, you know, it might be that we have brain-computer interfaces at some point in the next hundred years. And maybe I could plug in a brain-computer interface and it would give me, you know, access to the internet,

• 1:11:26Speaker 00

  or it would give me some additional memory capacity, or I could play the piano, which I can't currently do, or whatever. And slowly, I'd replace my neurons, one at a time, with an electronic equivalent. And you end up with the situation where if you, if you do it gradually, perhaps you do get a continuity of consciousness. But if you were to do it all at once, the question is, you know, would you just disappear? The philosophical question, which I've never seen answered to my satisfaction, is even if you do do this sort of gradual, not death, but sort of life by a thousand cuts, as you slowly insert the computer into your head. Like, is it definitely the case that I will still be alive at the end of that? Or will there be some weird cyborg Andrew Steele, who's like philosophically indistinguishable? As I said, you know, we could literally have this conversation, but somehow isn't me.

• 1:12:10Speaker 00

  And therefore, I am dead in the sense that we currently understand it. And I'm, until someone can convince you that that's the case, I'm happy in my squishy biological brain. Thank you very much.

• 1:12:19Chris Williamson?

  The maddest thing about consciousness is that if we weren't experiencing it firsthand phenomenologically, everyone that is listening understands what it is like to think and know that you are thinking, to be a bundle of matter that is aware of its own existence. If it wasn't for the fact that we feel that as an experience, we would be completely ignorant of the fact that it exists. That terrifies me.

• 1:12:43Speaker 00

  It's remarkable.

• 1:12:44Chris Williamson?

  Another thing, you just said there about the fact that terminating consciousness is something that is very meaningful when it comes to death. Does that mean it is a moral duty for all of us to live as long as we can and to maximize our life?

• 1:13:00Speaker 00

  That's an interesting question. It depends on your school of ethics, basically. And there's a really fascinating and knotty school of ethics called population ethics, which looks at these sort of questions population wide. And there's a huge amount of controversy. I'm not an expert in it. And there's a, you know, we could, if you get a philosopher on and you could talk about it for a couple of hours with them. But to give you two examples, one school of population ethics says that you should maximize utility. And what they mean by utility is basically happiness. You can, again, talk to a philosopher for 35 minutes about what they mean by utility. It's basically happiness. They want to maximize happiness. And what that means is you want to have the largest possible number of happy beings. And sometimes that means they're quite relaxed about death, actually, because they're not

• 1:13:43Speaker 00

  bothered about terminating consciousnesses as long as you replace them with other happy consciousnesses, because there's no sort of requirement for continuity. Another school of population ethics is called average utility maximization, which is that rather than saying we want to have the maximum possible utility, we just want the average to be the highest. And both of these lead to quite counterintuitive conclusions sometimes, because you could end up, if you want to maximize utility, I could imagine some world where we have 25 trillion people and they're all just above being utterly horribly depressed. But because they are just above that, when you combine them all together, the overall happiness is greater than a world of 7 billion people, who are all much, much happier than any of those 25 trillion are.

• 1:14:25Speaker 00

  So that's the sort of bizarre conclusion you get with maximizing utility. If you want to average utility instead, you can get another bizarre conclusion, which is that, imagine that I'm euphorically happy all the time. That's my disposition. Then if we murdered everyone else on planet Earth and I was the only one who has left, because I'm euphorically happy all the time.

• 1:14:43Chris Williamson?

  You brought the average up.

• 1:14:44Speaker 00

  Exactly. The average is like as high as it can possibly be. So clearly, both of these things lead to like these incredibly unpalatable moral conclusions, right? So. And basically, the jury's out. The philosophers are still arguing about it. And they may be arguing for some time because that's what philosophers do. But I think it's, yeah, it's really, really difficult to work out like what our moral duty is in this regard. And so that's, that's actually one of the reasons that I really care about aging. Because one of, like I said earlier, I think we can all agree that less death would probably be a good thing. And I think we can all agree even more than that, you know, even if you're chill about death, which, you know, some people are because they won't exist. Or they think they won't exist, then we all know that suffering is bad. And aging is the single largest cause of suffering in the world.

• 1:15:27Speaker 00

  So you don't need to, you know, break out the population ethics philosophers in order to get behind the idea that that's something that's worth doing something about.

• 1:15:33Chris Williamson?

  Yeah, that's the second order effect of somebody passing away is the people around them, the people that care, their dependents. All of those people are left traumatised and upset. And that is what led me to ask about, is it our moral duty to, to live as healthy and long of a life as possible?

• 1:15:52Speaker 00

  Yeah, no, I think that's right. And I think that's, that's something that it's almost a bit selfish to be like, oh, I'm not worried about dying because I won't be around. You're like, yeah, but everyone you love and care about will be around and they probably won't be that, you know, best pleased.

• 1:16:04Chris Williamson?

  You're totally right, man. Andrew, today has been really, really fun. Ageless, the new science of getting older without getting old.

• 1:16:11Speaker 00

  Oh, do you know what? You've got, you've got a pre-release copy.

• 1:16:14Chris Williamson?

  Oh, let's have a look at the, let's have a look.

• 1:16:15Speaker 00

  This is what it actually looks like.

• 1:16:17Chris Williamson?

  With a tortoise on it.

• 1:16:17Speaker 00

  You see that?

• 1:16:18Chris Williamson?

  Yeah, yeah, yeah.

• 1:16:18Speaker 00

  It's got a tortoise on it. Yeah. So that's our negligibly senescent tortoise. Oh, hang on, I'm pointing on the wrong side. That's my negligibly senescent tortoise. Yeah, there you go.

• 1:16:25Chris Williamson?

  Very cool.

• 1:16:25Speaker 00

  There's actually a quote from Andrew Scott on the front of the book as well.

• 1:16:27Chris Williamson?

  What's it say?

• 1:16:28Speaker 00

  It says, "Read it and prepare to think differently about your future."

• 1:16:32Chris Williamson?

  It's such a incestuous little community, this longevity thing, isn't it? Seeing Andrew Scott and you and David Sinclair, I can't get away from you.

• 1:16:43Chris Williamson?

  People want to check out your stuff, where should they go? The book will be linked in the show notes below. Of course, go and get it on Amazon. If you buy it through that link, you will be supporting this show at no extra cost to yourself. What else do you want to plug?

• 1:16:54Speaker 00

  You can find me on Twitter. I'm at Stato, S T A T T O. And I've also got a YouTube channel, which is youtube.com slash Dr. Andrew Steele, all one word. So yeah, check it all out.

• 1:17:03Chris Williamson?

  Amazing. Thank you, mate.

• 1:17:05Speaker 00

  Thank you very much. Have a good one.

• 1:17:22Speaker 02

  Mr. President, my company foreme of the explosion on our rig. On October 2nd. Causing massive water displacement and triggering a tsunami. They all heap the blame on me. Tom Cruise is. Digger got us into this, that's. And Digger's gonna dig us out. From the director of Birdman and The Revenant.

• 1:17:38Speaker 03

  What would happen if I stopped drilling? You stop, you freeze to death, that's what.

• 1:17:43Speaker 02

  With great power comes great deniability.

• 1:17:46Speaker 03

  I'm not the first man.

• 1:17:47Speaker 02

  Digger. See the trailer online. Only in theaters October 2nd. Rated R. Under 17. Not a minute without parent.