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

Episode Date: January 4, 2021

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 it? 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 - Get in touch. Join the discussion with me and other like minded listeners in the episode comments on the MW YouTube Channel or message me... Instagram: https://www.instagram.com/chriswillx Twitter: https://www.twitter.com/chriswillx YouTube: https://www.youtube.com/ModernWisdomPodcast Email: https://www.chriswillx.com/contact  Learn more about your ad choices. Visit megaphone.fm/adchoices

Hello friends, welcome back. My guest today is Andrew Steele. Scientists, writer and presenter were talking about an absolutely fascinating book that he's just written called Ageless. Aging is a phenomenon that we're all familiar with and is completely taken for granted as a fact of reality. But do we actually have to accept it? So today, expect to learn why curing aging might be easier than curing cancer and all

of the diseases, the unfortunate truth of fasting for longevity, why the next decade will be the most exciting for lifespan research and much more. I love uncovering things that we all take for granted is just a normal part of everyday reality and then looking at them from first principles, Andrews absolutely awesome and he's got his own mic setup so it just sounds so lovely. Props Andrew also don't forget I don't really push this too much but if you enjoy the episode support the authors that I have on the show by buying their stuff it's always linked in the show notes below and if you buy through that link you'll be supporting the podcast at no extra cost

to yourself because Amazon need to pay me a little tiny little bit of commission but not much and it doesn't cost you any more. So yeah go and support them by their stuff if you enjoy the episode you'll enjoy the book. But for now, it's time to work out why we get old and how we can stop it. With Andrew Steel. Ladies and gentlemen, welcome back. My guest today is Andrew Steele. Andrew, welcome to the show. Hello. Thanks for having me. Pleasure to have you on. What is aging? That is an excellent question. There are many, many different ways you could define this. And I think every different scientist

to give you a different answer. But I've got two ways of thinking about it. One of them is statistical, one of them biological. And the statistical way of thinking about it, which I think is the most sort of catch-all 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 time. So the longer you've been alive, how much does your risk of death increase? So take the example of humans. If you're in your 30s, your risk of death is about 1,000 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 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. It's 200. It's 200 times why I'm right. Sorry. It's correct.

It's correct, Andrew. Where the internet, you're here because you're a scientist, not because you're a mathematician. And what you find, actually, is that the better people are at maths in terms of the proper theoretical hard core 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. I remember my...

So that old housemate did a PhD in pure mathematics and he once ordered a 4c to taxi for five of us because apparently in pure maths you count from zero? Yeah, yeah, it's off by one error, classic computer programming as well. Unbelievable, man. You spend all this time doing maths, you can't count to five. I know. Got a PhD, can't even manage it. So what I was saying, yeah, so humans, the sort of way to sum up all that stuff that I just failed to out of him 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 if that's, you know, this is called a 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 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. 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, 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 tend to increase with age, all of these things. 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. 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 statistic when we started with. Yeah.

Is there a cultural blind spot around aging, like hearing the word cure and aging in the same sentence is not very common. Yeah, I think there is and I've used the word cure slightly to the chugrin 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 of her scientist described 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. Are there not things we need to sort out first, like cancer and heart disease, not surely they're easier to fix and quicker to happen than aging? Yeah, the strange thing is, it might actually be easier to sort aging than to sort all of those

diseases individually. So the reason that our risk of death doubles every eight years is it does. You've got a 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 gray hair, they're sort of superficial changes. They drive the 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 international classification of diseases, 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 addition. I might have got that slightly wrong. 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 things that they can't say, there's loads, you know, every single subtype of every cancer in every organ, there's all the different ways that you 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 or we can go after the root cause, the thing that causes 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. Yeah, you said much of modern medicine targets symptoms a few steps removed from the root cause of the illness. I guess it relates to what you're talking about there.

Exactly. Yeah. 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. I know 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're 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, it's 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.

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 hunt, a 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 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. Yeah, so it's hard to get the exact numbers

that 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 modernize. Like imagine if we were running that sort of gauntlet and I kept childhood in teens, it's crazy. 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. Now 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 maximizers, right? And truly this certain end to life is a bit of an error. Like, why is evolution not made us immortal?

Yeah, it's an interesting question. And so there are two aspects of this. Firstly, is there an adaptive advantage to dying? And secondly, is there an adaptive advantage to aging, which is sort of, they sound like the same question, but they're not. So to answer the first one of our 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 half of my mum, half of my dad,

and that DNA is what we're stuck with for life, more or less. We can't adapt to be better, faster, stronger, we can obviously train, we can eat well, we can do whatever we like to try and improve our fitness, but ultimately, west up with the genes that we've got. So if you want to evolve, you've got to have kids and those kids are different from you in a few different ways, different from the part you had the children with, 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 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, you know, go in and change its own DNA, which isn't a thing that organisms

can do. The changing in DNA occurred you to birth, not death. Dying doesn't seem to be a part of reproduction. No, it's not, but imagine, imagine that where, you know, cheaters are on the savannah and we're really well adapted for our particular evolutionary niche. We're really good at running fast. And then we're also immortal cheaters. This is a love it already experiment, shall we say. So we're immortal cheaters running around

the savannah, you know, eating gazelles. The problem is, you know, say, for example, there's a massive famine of the particular kind of tree that the gazelles we most like to eat. And so all the gazelles die and we eat the handful that are still left. Suddenly, what we need to do is adapt our environment to dramatically change. We haven't gotten any gazelles to it anymore. But because we have got our fixed DNA, we can't adapt. We've still got sharp teeth, we're still 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 every 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 than eventually, they might become completely vegetarian. This is 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 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 had changed around it, and it would be doomed that way. 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've essentially unchanged for millions and millions and millions of years. They're just landed perfectly on their evolutionary niches, you called it. And I guess that that would be the only way that you'd be able to survive, that the role of the dice would be like 26 is 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. 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 fossil. What's the other half of why we die then in terms of evolution? So in terms of evolution, aging is an accident and so you're absolutely right to sort of couching the 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, otherwise animals would slowly evolve to become huge monsters, and they clearly don't do that, right? They optimize themselves 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 cheaters, not immortal anymore, but we're back to our cheaters 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 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 first slightly better camouflage, 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 strong and weak and all different kinds of animals adapted very differently for different environments.

So aging is exactly the same sort of thing. In that it's an evolutionary compromise because if you build an animal that's effectively immortal, so it doesn't have a risk of death, it doesn't change your time, for example. 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 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 get into, catch up with those gazelles. So there's this sort of, 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 shorter a lift one's going to win,

because it puts less energy into maintaining its body, and it can put more energy into something that's more evolutionarily important in its niche. It's like a mouth-usian trap, a little bit. It's like you're going to be out competed by something else that has a higher chance of not only surviving but also reproducing. And if your survival is at the cost of your reproduction, it's not happening. Yeah, that's exactly right. And I think this phrase, survival of the fittest, is really become like a part of popular culture. But actually, what we should say about evolution

is it's reproduction of the fittest. That's the key point. 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. Exactly. And like at some point, a bus or a cheetah is going to come along and get you and you're gone. You might as well not have existed. I tell you what I found out this year that I thought was fascinating. It's the non-zero existential risk from natural risks that we have, that means we have to have technological progress. So this is from Toby odds the precipice. And there's a lot of concerns at the moment around

are we moving too quickly towards artificial general intelligence or bio weapons or nanotechnology, and we're all going to get turned into grace, ludge, 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 super volcano's 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? That's just like a macro aggregated version. You need to have this cost payoff between the two. Yeah, definitely. I think that's exactly right because there are some problems that we can't evolve our way out of. Like, we just, not, if we hadn't developed computers and spacecraft and all these different things, like what on earth are we gonna 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 gonna get us out of that situation. So fingers crossed that we can sort it ourselves. So why do we age? Fundamentally, that's exactly why it's this trait, this evolutionary trade-off. And 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 if I would 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 gonna mean that they have four kids and they 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 gonna, I mean, they have four kids, and they have eight kids,

whereas my one kid's only gonna have two kids, and it's constantly gonna be a step behind. And that means that in an environment where, you know, eventually I'm gonna get hit by a bus, so I'm gonna get eaten by a sabotee of cat, or, you know, just gonna dive in infection in prehistory, then your weight of numbers is gonna outweigh my slight extra lifespan advantage. And ultimately, evolution makes this trade off. And unfortunately,

it's come down with us aging. What's the process of us aging? What is happening inside? Why does it? Why does it do what it does? It's a variety of different things. It is basically a load of things falling at our balance, a load of things getting broken. And it's quite a complicated thing, right? So I think there's, there's, there's been a lot of theories of ageing that have tried to ascribe it to a single cause. But I think what the hallmarks show us, and I talk about the hallmarks and my book in a slightly modified form, they've got nine, I've got ten, I sort of, I combine a couple and I add an extra couple.

But it's basically the same kind of thing because obviously the process is very similar. But it's everything from the DNA inside our cell is 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 behavior to change. So it's a complicated 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.

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? So it depends on the tissue. It's really interesting because like, so our guts are literally turning over every few days. Okay. 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 ten 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, 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 protected, there's something called the blood brain barrier that keeps almost everything

out of your brain that isn't needed. And that means that a neuron is in a really quite a safe environment. And so apart from a few special cases, like you're factoring neurons, the neurons that are responsible for your sense of smell, they turn over really rapidly because they're exposed to outside environment, they're exposed to your sense of smell. They turn over really rapidly, because they're exposed to the outside environment, 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. That's fascinating. I thought I've seen something probably on Instagram that was like every seven years or so, all of yourselves turn over. But now everybody that's listening has it in the tank to say, actually, there's some

neurons in the blood-beam brain barrier, and I think you'll find they're exactly the same. 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? I think the craziest, in terms of actual lifespan, tend to be a little bit further from humans. So the longest-lived vertebrate between animals with a backbone is actually 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 chemical analysis that the oldest green land 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 sort of tree of evolution, tree was an appropriate choice of wood actually because we think the longest lived single organism on the planet is a tree called a bristle cone pine. It's in the White Mountains in California. It's a top secret location because they want vandals to gun chuck down this like incredible piece of earth history. It's a secret tree. Shit the bird. Yeah, a secret tree. And 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 assaspling before the pyramids. That's just absolutely mind-blind to me. That tree has basically seen the whole arc of human civilization from a top of this sort of windy, arid mountain top in California. That's unreal. What about this hydra thing? 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 we've watched

like loads of them live, to how many would still be alive after a really long time. So hydra, they're these tiny fresh water creatures. They're incredibly simple. So they basically got a mouth at one end and a bum at the other and not great to allow us 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 and get too high. You can chop it into four, you will get four hydra. So it has this incredible, you know, 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 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. They're again, we obviously haven't done the actual full-empics experiment that 10% of hydra would still be living after a thousand years if the death rates you've observed so far are accurate. Which is just bonkers, because that's that 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. Is this, like, tardy grades as well? They're pretty hardcore, aren't they? They are pretty hardcore. I actually don't know if we've got any good longevity date

on tardy grades, I've not seen it. They're certainly hardcore in the sense that they can survive ridiculous environment and hard to say. Same levels of radiation, vacuum, terrible chemicals, and they just basically, I think they just dehydrate themselves and turn themselves into this super hardcore, remnant tardy grade that as soon as you just you just add water you get the target back again

Yeah, it is like those sea monkeys that used to get as a kid. Yeah You said that the effect of fasting is one of the most universal in all of biology. What's that mean? So we've observed the first proof that we had the aging could be changed in animals The first proof that we had, the ageing, could be changed in animals, was some experiments that were, that they were sort of kicking off a bit around the early 20th century, with the first proper formal experiment on this was done in the 1930s by a guy called Clyde McCuy. 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 rats were being given. They just kept living. So they lived about 40, no, hang on, they lived about 80% longer the rats. And not only did they live longer, they live 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 nautopsy after those rats were dead, they basically looked the same, they looked indistinguishable from the rats that had died, you know, 600 days previously to cut in 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 and dogs know bizarre creatures that live in pond water. And the only question mark really is how to what extent it works in humans. And we've got to make 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 early on. I try 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, 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 bio-gyroontology community. Fasting doesn't actually make you live longer but it certainly feels like longer and so 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 scientist and and outs, oh, you know, we've done the study now, we've worked without the dietary restriction, it works and every other organism I've fought for us. Where's your money on this if you had to put a bet on?

I think it's probably gonna turn out that it improves health but doesn't do that much on lifespan. I'm not gonna say it wouldn't give you a year or two, but it's not gonna, because I think the best evidence for this, quite a size for many complicated studies, because in that there have been attempts to do this properly, proper medical research type, randomised trials where you give some people, reduce some people's diets and leave other people eating normally and see what the difference is. But quite apart from these 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 our 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. It would be, I mean, for the long-gevity, our slash longevity on Reddit, 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- Is that bonus, yeah? Potentially been twice as hungry. So, yeah, it is a big trade off. And just going back to that rat study, there was calorie restriction and fasting, a 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? So this is so naughty, and I think there's a real problem actually with the animal experiment. So mice is the one that they've done a bit more experimentation in now, they're the more common lab animal. And there's been, you know, scientists try to distinguish the effects between dietary restrictions, so eating less all the time and intermittent fasting. And again, this can come in a huge load of forms, like do you eat every other day? Do you do the five two diet? Any 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, eight 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. 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 the work day, give them their rations to half their food if they're on dietary restriction or 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 astonished me, I was chatting to a scientist about this and they were saying, actually, we recognize this problem. And just now, literally, in the last few years, they've started doing some experiments. I don't think any of you have yet been published with automated feeders like you dogg or you can't, if you're away from home. And it just, it's head slapping. Like, how have they only thought? It's not as though this is

2010 technology. We've had automated pet feeders for decades, haven't we? And yet for the first time, there's been enough interest in sort of distinguishing the differences between DR and IF to actually do the experiment properly and find out. We only put wheels on luggage about 30 years ago. So 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 to 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? 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 favorite 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 Haiflick and he was doing these very sort of cells in a dish of experiments, they're very far removed from actual organisms and humans. He was just growing these cells in a dish. What he noticed was they're dividing, dividing, divide what cells do and then after about 50 divisions they just stop. And not only did they stop dividing, they looked weird under the microscope, they 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 a non-expert can see, is this sort of weird, blurgy, splaid out. It looks radically different from a non-senescent cell. And as a result, because these cells seem to be old in the sense they've 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 was aged cells. And these were of interest, and people wondered, you know, that's the train I 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, the Mayo Clinic in the US got some mice that have been genetically modified and they've been genetically modified such that they had an extra gene. And what that gene did was it meant that 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 an SNES and cell?

If I am, I'm going to kill it. So it's sort of a suicide switch, but just for SNES and 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, didn't make them live longer because this first experiment was done in a special, and they had another genetic modification that made the 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 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 healthier, they get cancer later, they get cataracts later, they have better fur, which is obviously crucially important to all of us. They are, you know, they're more cognitively, 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 and never look to see what's going on. But an old mouse has been given these senilellitic 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 that this is one hallmark of aging. We can go after the rest of them, then we can start to slow and reverse aging in a multitude of different ways. And all together that should slow our aging down basically overall. 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 sort of fit in? 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. Say 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 gut, so 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 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, but what's surprising is almost how lucky we've got with these first round of seniletic 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 them might live longer, live younger. I don't think this is going to, this is going to be the end of semantics. I think we're going to have to refine them. But we have struck surprisingly lucky, at least in mice, with these first treatments. What about stem cells?

Yeah, we're definitely going to need more of those. I think, yeah, so there are a particular example. If you were to 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 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 turning over at the rate they should be turning over.

It's going to be an increasingly complex system to continue to move. What about like ongoing repair running? Is there anything we can do there? Yeah, and I mean, the thing is, 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 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 one thing that you can do, for example, you've probably heard of the apigenetic clock, I think you chatted with Davidson Claire about that, and the sorts of treatment that he works on where you insert these genes and it reverses the apigenetic clock can reverse cellular senescence as well, and it'll be interesting to see whether or not that's a wise move because often senescence 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 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. Rather than adding a gene on, is there a way to upgrade gene's wholesale? Yeah, so gene therapy is coming on. It's not quite at the point where we can inject a new gene into every cell of your body yet. That's a real challenge. But certainly the dream is that 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 June 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 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 shapes, so sort of shaped like a sickle, I think I said in a hammer and sickle, so let the sea 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 to 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. Forbustus I, is the word, I'm not entirely sure, I'm not an insect biologist, 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 womb. 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 of 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, and 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 removing cells, modifying them outside the body, doing gene therapy, putting them back in. It's not at the stage where you 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, and actual cell therapy in the clinic. Will the cure for aging arrive in time for me and you? I think it could do. I don't want to make any guarantees,

but I think 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 who are active 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, deep mind this company that are part of Google. And now it's that 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 we'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 huge model, a computer model that understands the whole of the work into the human body, all of our DNA, all of our proteins. We've got 40 trillion cells in our body all working together. You

have to model every single one of those. And I just thought, this is crazy, the cure of ratings is never going to arrive in time. But actually, if you think that kind of idea is a bit pying the sky, it's 50 years away. Imagine I'm in my 30s now. I'm fully expecting, even if nothing happens in medicine, that 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 senolithic 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 let's imagine that you live an extra five years as a result of all that stuff, and five years in good health. That means 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 we might be alive in time to take

them basically. So I don't think, I don't want to guarantee at all, we 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 and 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. It's like biology or longevity's got a hard problem.

And that heart, or a, how would how do 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 or it may not exist Yeah, it'll be a fascinating area of research presumably as well 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. If I wanted to be really conservative, I'd think in the year 2000 people's risk of death is not going to depend on how long ago they were born.

You're three thousand. So in the year 3000, that definitely, I'm saying that to be so thoroughly on controversial. 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, 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 and 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. 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's found. Exactly. Even if we don't get as far as a cure, like every year you live in good health additionally, there are gonna 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 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, they're very keen to talk about like really, really long lifespans and stuff that 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 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 got an infectious disease when they were 20, there would have been just 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 what I'm talking of, you know, we didn't put wheels on suitcase until the 70s. We didn't invent chest compressions until the 1950s or 1960s. And they certainly weren't in white 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 unbeat it for it effectively? And yet, it took us thousands of years as a species to come to that realization. And so, what that means, I've got quite a sidetrack, 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, 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 a thousand or ten thousand or a hundred and two, the fact is every year you stay alive longer is another opportunity for some medical breakthrough to happen that could benefit you. Let's say I want to live as long as I can. What do I do? I want the full Monty. I think at the moment, a lot of it is just follow the basic health advice.

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 research, 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 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, it increases this process called inflammation which you 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 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 all of us are really, I'm fascinated by diet reading, we're talking about dietary restriction, I got obsessed when I was writing that bit of a book being like, what is the optimum diet? 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 you 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 getting to read my book, 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 gonna get a critical match.

We need voters to know this, we'd politicians to know this, and that means they can give money to the scientists to a 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, so 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.

What about exercise? What's the most optimal form of exercise that you found? And again, that's so tricky. I think something that I certainly personally neglected with 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-agenerians to people in their 90s strength training, and they were able to walk fast, they were able to lift heavier weights. It's not like they were going down the gym and powerlifting or anything like that, but their quality of life was substantially improved by this strength training intervention. And so it's never too late to start, and also 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. 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 it's going to work, but it's probably not going to work. So I might as well do it. Yeah, and that's the really frustrating thing about it,

isn't it? It's infuriating, because 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, it's just so tiring all of the time. And it's not like there are no disadvantages at all. So the, 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. 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 drop out of the trial because they were losing bone mass. They had someone drop out of the trial because they were getting a neemic, 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 dion anyway. Or coronavirus these days, of course. So, it's not, unfortunately, it doesn't quite come down to Pascal's wager, because firstly, it's just tiring and really dull. And secondly, there are these nasty disadvantages. I mean, it's just not a no-brainer to try it. 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 is a good friend of mine. She consistently does like four day fast or seven day fast and stuff, which is just, yeah, that's another level, but. It really is. 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 simple as... I'm really mixed. Something that happened to me in exactly this way, say calorie restrictions really hard. Intermittent fasting is still quite high, I can try and not eat for a full day,

it's really difficult. But the 16-8 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 last month or the month before, and literally the week we started doing it. And it's quite doable. So actually my wife and I decided to try that at the beginning of, I think it was, I can't have been, 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, just skip breakfast, starting at 12, then make sure you get your food in before 8pm. It's, I was a bit hungry in the mornings, but I often used to skip breakfast, you know, as a young young adult, right when I was irresponsible. So that's some, 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 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 didn't do anything. The people who are in the control group

and the people who are in the experimental group doing the 16.8, they both had about the same trajectory of their weight, their inflammatory markers and their blood, about the same, their cholesterol was all about the same. And you know, that's not nails in the coffin, but the scientists who did the experiments, he said, I was taken in by 16-8 fasting, I was completely convinced by it, but now he's done this experiment, I'm stopping today. You are announcing on everyone's party today, it's really annoying, it's not like and I don't want to. I mean, 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 some really compelling arguments made by people who are like, dear advocates. So for example, this study in Resers Monkeys, there are two studies done. One of them was done at a University of Wisconsin, and one of them was done at the National Institute 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 park that.

We can still potentially look forward to healthy lives, but let's talk about longevity now. 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. What's DR? Because I'll 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 this is so complicated, right? It sounds like a luringly 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 in what exact way that conferred those particular benefits? And that's how you end up in this

mess. And 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, are relatively uncontrolled as unfair, but they're fed a natural diet of like fish and grain and various bits and bobs, which by its nature is uncontrolled, because obviously you can't create a fish that has a particular combination of nutrients inside every single time. And the monkeys in the University of Wisconsin version were eating these sort of science purified pellets so they had 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 out of it 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 the 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 were on a restricted number of these pellets, was healthier and lived longer. 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, and perhaps simplest 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 there was Wisconsin monkeys gorging on 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 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 late adulthood and they also had monkeys from all different parts of the world. And this, if there isn't effect, this could potentially obscure it because they found that dietary restriction works differently in different strains of mouse, for example. And so you can imagine that an Indian, Macachan, an African Macach 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 completely ran on everyone's parade. 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 do these experiments. They're trying in good faith to replicate these ideas. They had slightly different approaches granted and there are various things you can quibble about. But if this doubles lifespan, we'd know about it, right? One of them might be a bit less than the other one, but 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 ten more years, but if you're already in a basically healthy diet, I think it's hard to expect that you're going to like dramatically alter your lifespan through DR. 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 and off. And now we're wrecked. What's different? Yeah, it's rubbish, isn't it? The way to reassure yourself a little bit is part of the reason is probably that we are, we're incredibly long lived for our size. We're pushing the limits of that already.

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 life zones 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 so firstly, I think these results are much more variable than is 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. 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 eye-staffed act of desperation. So the theory goes, and it's not entirely supported and there are DRF opponents 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. Because if you're going through a famine, you need to survive much longer, you know, a significant fraction of your lifespan in order to get to a point where you can have kids in 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 this sort of tight correlation between lifespan and size and the tight correlation between lifespan dietary restriction response doesn't really hold very clearly. So dogs, for example, which we've also tried dietary restriction in, has a surprisingly

small effect on, 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 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. 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 while this could have been different, and that could have been different. So, yeah, it's strange that something that's, let's say, the prime vector of so much suffering, and a universal ubiquitly 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 St. Clairstack? 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.

It's like re-growing optic nerves and magic like that, isn't it? But crucially, that was with gene therapy rather than with a drug. I'm actually 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's clearly, you know, something that it's 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 moving extremely pedantic scientists. 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 ten years. And you're aging at

the moment, relatively under control, right? You know, 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. Take everything. Because it take absolutely does everything. Don't eat. Take all the drums. It does turn into much more of a Pascal's wager at that point. Because so the, I think the one that I'm 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 that 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 60-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 less overweight, they tend to be a bit fitter, they tend to be healthier, they tend to have less other diseases. And yet, even still, the diabetics on metformin in a couple of studies of marginally outlive 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 were 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 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. One of the things that fascinated me, especially after my episode 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 episode, 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 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 the 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? It's a good question. I think there's obviously a huge spectrum. I mean, as you can see, as you said earlier, I caveat everything. I'm 100% like extremely cautious scientist, 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 fascinating bit of psychology because I'm not motivated by death per se. I think I got interested

in this stuff because I realize that 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 that sort of thing that fundamentally got me into it. So I find it hard to like peer into the psychology of someone who, I mean, death can be scary. It's a bizarre thing to think, ceasing to exist. And I think this philosophical idea that you won't know, it doesn't matter because you won't be there. I still don't like, don't particularly enjoy period to the abyss, 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 almost nothing where if you were pursuing some goal that was going to reduce the amount of death in the world,

that anyone would criticize it. 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 scientists saying that. And yet, there are some people who really push back in the other direction as well.

So I think 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, yes, it's really fascinating that we're now at a point in history where, you know, we're not sewing monkey testicles to people to try and make them live longer. We're not like giving them a way. Combinations of herbs and that if it's certainly, yeah, in the 1920s, there was

a big snow and trying to work out where the monkey testicles are. Yeah, yeah, where? I'm actually not 100% it was quite hard to do. It wasn't a straight swap was it? I don't I don't think so. No, I mean the thing is you probably want to keep your own wouldn't you because they're useful a monkey's A monkey testicles the ones that are huge. They are aren't they? Do you know what I'm actually not sure what the logic was at all behind this idea. Anyone who knows anything about monkey testicles, please leave it in the comments below. Yeah, please please write in. Have you had enough to get lots of correspondence? 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? Do you know what? I don't think it would make much difference. And that sounds like a strange answer, but I think, because 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 out of date, or when you 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 wanting to sound like some kind of headiness, I just live it day to day, like mostly, I get up in the morning, I have a 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. And so I think if I was going to live to 160 or 560, I just, I think I'd probably continue living day to day in week to week, like it would change some things about the way that we function 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 in a matter of difference to how we live.

One thing I don't think people plan for the long term that much now. 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 thing that I'd considered was 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% so 40% to 50% of the way there. Yeah, got bad. Yeah, you know, I thought 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. Yeah, definitely. 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. 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, two, three hundred 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? Transhumanism and artificial intelligence, uploading our minds to the sky net and getting an anal swatching eager down, versus beating aging to get us to live over 200 years, which one do you think comes first? I hope we do it biologically, and the reason is actually quite philosophical. I say I hope we do it biologically unless I'm in less 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 specially 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 the 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 of giving you all the same damn answers or at least ones that were indistinguishable

in terms of cognition. 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 cut that off

and 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, you don't need it anymore. You've got absolutely no guarantee that that consciousness has continued.

And philosophers have got some ideas of how to get around this, which is, for example, it might be that we have brain computer interfaces at some point in the next 100 years. And maybe I could plug in a brain computer interface and it would give me access to the internet 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 a situation where 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, would you just disappear? The philosophical question, which I've never seen answered to my satisfaction, is even if you do do this or 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 and therefore I am dead in the sense that we currently understand it. And I'm until someone can convince me that that's the case, I'm happy in my squishy biological brain. Thank you very much. The maddest thing about consciousness is that if we weren't experiencing it first-hand 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. It's remarkable. Another thing I think, 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?

That's an interesting question. It depends on your school of ethics basically. And there's a really fascinating and naughty 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 if you get a philosopher on it, you could talk about it for a couple of hours of 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 us 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 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. 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 the one is imagine that I'm, you know, you're furrically happy all the time. That's my disposition. Then if we murdered everyone else on planet earth, and I was the only one who was left, because I'm euphoricly happy. Brought the average up. We've just, 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 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, even if you're chill about death, which some people are because they don't exist, or they think they will exist. Then we all know that suffering is bad. And aging is the single largest cause of suffering in the world.

So you don't need to break out the population ethics philosophers in order to get behind the idea of that's something that's worth doing something about. Yeah, that's the second order effect of somebody passing away is the people around them, the people that care, their dependence, all of those people are left traumatized and upset. Yeah. And that is what led me to ask about, is it our moral duty to live as healthy and long of a life as possible?

Yeah, no, I think that's right. And I think that's something that it's almost a bit selfish to be like, 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 best pleased. You're totally right, man.

So, Andrew, today has been really, really fun. Ageless, the new science of getting older, without getting old. Oh, do you know what? You've got a pre-release cut to. Let's have a look at the early one. This is what it actually looks like. The tortoise, aren't you?

Yeah, yeah, yeah. It's got a tortoise on it, yeah. That's our negligible senescent tortoise. Oh, hang on, I'm pointing on the wrong side. That's my negligible senescent tortoise. Yeah, there you go. Very good. And there's actually a quote from Andrew

who's got on the front of the book. What did I say? It says, read it and prepare to think differently about your future. It's such an incestuous little community, this long-cherody thing, isn't it? So, in Andrew Scott and you and David Sinclair can't get away from you. People want to check out your stuff, where should they go? The book will be linked in the show, not to below. Of course, go and get it on Amazon. If you buy it through that link, you will be supporting this show at NoEx for a cost to yourself.

What else do you want to plug? You can find me on Twitter. I'm at Stato, STATTO and I've also got a YouTube channel, which is YouTube.com slash Doctor Andrew Steele, all one word. So yeah, check it all out. Amazing. Thank you, mate. Thank you very much. Have a good one. I'm around. Easy as that.