Can we cure ageing?

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BBC Sounds, Music, Radio, Podcasts.

Hello, I'm Robin Inks.

And I'm Brian Cox, and this is the Infinite Monkey Cage.

And today's topic is one, well, frankly, one that is of a lot more interest to one of us than the other, because regular listeners and any fans of Brian Cox will know that despite the fact that he is a professional physicist, he has refused to obey the second law of thermodynamics and has not aged now in 34 years.

This of course is intensely unfair because for the balance of the universe, I have had to plunge headfirst into disorder and now basically like a sociology lecturer on his fourth divorce.

It's true.

And this is despite the fact that I am actually younger than him, right?

And this is

which genuinely, when that got told to someone in an audience in Pittsburgh, a child next to them audibly gasped.

It was Brian thought he would shock the audience with some of the kind of counterinstinctual ideas of quantum mechanics, but no, that meant nothing to them.

How can that old guy who looks like the corpse of grizzly atoms be younger than brian cox it's actually true this is true we're checking in for the flight and uh the person at the check-in desk said do you want to sit next to your dad which is not yet

honestly

not true at all

Regular people who watch Brian's physics documentaries will know he does make up a lot of stuff.

And

what actually happened, this is true, it's halfway through that story.

It happened when we were on the way to Canberra and it wasn't at the check-in desk that they thought I was his dad, it was when we got to the security, because when we got to the metal detector, Brian got scared because he doesn't understand magnets, and I had to hold his hand as we went through, and that is why there was the confusion.

Shall we go?

North Pole, South Pole.

Oh, I don't find this thing wonderful at all.

Anyway, so

Radio 4 listeners will know that that's not an impression of me.

It's basically Alan Bennett.

Isn't it?

No, they know, they know the version of Alan that I do every now and again.

Brian Cox arrived on a unicycle again, pointing at something he said was a star that was clearly a candle he placed on the end of his nose.

Look at me, mummy, look at me, mummy, he kept shouting.

I'm an astronomer.

Should we get back to the science?

Oh, I don't think we've got anywhere near the science yet, so I don't think we can get back to it.

Today, we'll be discussing why Robin looks so ancient.

We're looking at why we age and whether the science of biogerontology will offer effective solutions to some of the causes of death that arise as a result of the ageing process.

Joining us today are a professor of genetics, a computational biologist, and the winner of the Melbourne Comedy Festival Piece of Wood Award.

And they are.

I'm Andrew Steele, and I'm a computational biologist and author of Ageless, the new science of getting older without getting old.

And the thing that's most surprising me about getting older is how everything seems to be changing exponentially.

There's my risk of cancer, my risk of death, and also the exponentially increasing rise of computing power and my own embarrassment at my previous fashion choices.

I'm Linda Partridge.

I'm a director at the Max Planck Institute in Cologne in Germany, which works on the biology of aging, and I'm also a professor at UCL.

And my professional passion in life is the biology of aging.

I've worked on it for decades, and I'm fascinated by it.

And the thing I found so about getting older is it gets so much easier to get up in the morning.

I'm Sarah Kendall.

I'm a stand-up comedian.

I write for television and I perform on television.

It's not quite up there with Professor at Usel.

What I'm really coming across is you're rather ashamed to be on the radio.

I'm very ashamed.

What's most surprising about aging is how brutal the high-definition close-up is.

And this is our panel.

Andrew, let's start with you.

Because you, I can't remember whether you've had two or three different disciplines.

Because you were, I thought you started off in biology, then you went into physics, and now you've become fascinated in the science of aging.

So, I started off as a physicist.

I loved magnets when I was doing my PhD, and then I became a computational biologist.

And the reason is I actually changed career because of a graph.

And this graph, it's quite a simple one because this is radio.

I'm going to have to describe it rather than show you.

What it is, it's the graph of your risk of death depending on how long ago you were born.

So let's describe how that goes through lives.

You start out when you're being born.

You have about a half a percent chance, if you're lucky enough to be born in a rich country, of not making your first birthday.

But actually, things carry on getting better and better from then on until you reach the illustrious age of 10 years old.

And current 10-year-olds have an incredible title.

They are the safest human beings in the history of our species.

They have a less than one in 10,000 chance of not making their 11th birthday.

But unfortunately, it's all downhill from there on.

I'm 36.

My odds of death this year are about one in a thousand.

And I quite like those odds, because let's think about that for a moment.

If that were to continue for the rest of my life, I'd live into my thousand and thirties on average.

But of course that isn't what happens.

Actually humans have something called a mortality rate doubling time.

It's the amount of time it takes for our risk of death to double.

And for humans, that's about eight years.

What that means is that one in a thousand can carry on doubling and doubling and doubling and doubling.

And if I'm lucky enough to make it into my 90s, but unfortunate enough that medical technology doesn't advance in the intervening time, I'll have a one in six chance of not making my next birthday.

That's life and death at the roll of a dice.

And so there are two ways you can look at this.

You can look at this as a normal human being and go, my God, that's terrifying.

I've got this exponential wall of mortality and disease coming to get me.

Or you can look at it as a physicist.

And you can say, this is fascinating.

What is it about this incredible, you know, the facet of human biology that means we've got this incredibly universal process.

We've got an increase in the risk of all kinds of different things that happen to us as we get older.

And it's surprisingly universal.

Like if I were to go and find, if I were to grab a random member of the audience, or if I were to go into the Amazonian rainforest rainforest and find some undiscovered tribe, they wouldn't have a great deal in common necessarily, but their mortality rate doubling time would probably be eight years, because that's a fundamental thing about being a human being.

And so I just thought, I've got to get to the bottom of this and try and do something about it.

See, that's a beautiful thing, I think, about science, which is you can deal with some of the most terrifying ideas, but by analysing them, by staring at them for longer, they can become less threatening even if they remain imminent.

Definitely.

And the idea that there might be some kind of ticking clock inside our biology.

I think what really inspired me as well, on top of the fact, you know, staring down my own mortality, was looking around in the animal kingdom.

You can see that there are animals that, by this statistical definition, this mortality rate doubling time, they literally don't age.

So let's take the example of a Galapagos tortoise.

These beautiful animals, they can live to the age of, I think the oldest on record is 175.

This was a tortoise who was brought back from the Galapagos Islands by Charles Darwin.

She outlived him by over a century and eventually conked out of a heart attack at about that age.

And what was most incredible about her wasn't how long she lived, wasn't how long her species tends to live.

It's the the fact that they're something called negligibly senescent.

So negligibly, not much.

Senescent, just the biological word for old.

And these animals, they have a risk of death.

It's basically constant as adults.

That means that they don't age.

And not only is their risk of death constant, their risk of disease is constant.

You can tell from a tortoise, they're not getting any more frail.

They're sort of, you know, still able to get around.

not necessarily that fast, they are tortoises.

But nonetheless, they're equally as active in their 150s as they were in their 50s.

And so what that shows us is, you know, the second law of thermodynamics doesn't force us to age.

And even the laws of biology don't force us to age.

So hopefully, you know, if we could come up with the biomedical science, maybe we could push humans to be a little bit more tortoise and reduce that risk of death with time.

So I presume battle reenactors will live for a long amount of time because they move slowly in armour.

So does that mean that they'll...

I think, yeah, over evolutionary time, if they carry on reproducing and remain in a safe environment, this is how we think aging evolved, basically.

Animals that are safer from external threats, so perhaps battle reenactors, as they breed with other battle reenactors, because they're at less risk from death from other causes, biology will gradually drag out that period of senescence and allow them to live longer and healthier.

And that means they'll probably reproduce more slowly as well.

I guess that sort of fits in with your theory.

Well, I don't think battle, that's the trouble.

Battle reinactors find it very hard to reproduce because it's very hard.

A hinged cog piece is very, very difficult, and once rust sets in, so we probably need to factor that as well.

Well, I was hilariously going to say, why don't we start breeding with tortoises?

But it wasn't worth it, as you can see.

Well, Linda, given Andrew's

observation that there there doesn't seem to be anything across all species that says that everything must age,

what what is it about humans?

We could start with the definition really, what what is aging?

Without just pointing at Robin, what uh

do we have a a precise definition of what

yeah Andrew hit the nail on the head with that, which is that aging starts at puberty.

So I think it's easiest to understand what it is, or I find it easiest to understand by thinking about evolution.

And basically if you if you die before you start reproducing at all, then you're going to lose everything.

But once you've started reproducing, it becomes a problem, but progressively less of one because you've got less reproductive lifespan in front of you.

So, what happens is that the natural selection keeping us alive, making sure that we do the right thing at each age, actually weakens as we get older as adults progressively.

Again, for the reason Andrew said, there's no point building a body that can live for 300 years if on average you're going to get taken by a saber-toothed tiger within 30, or whatever the risk is in your environment.

You only make your body last for as long as it's going to have the opportunity to last, given the kind of circumstances in which it's living.

I think that's really how I think about it.

And it does mean it's all downhill from puberty, unfortunately.

Can I ask a question just about when you said the tortoise that lived 170, what was it that actually killed the tortoise in the end?

Like,

does the heart inexplicably, is there

an electrical impulse that can just mysteriously stop?

Like, or was there some like sort of associated morbidity that killed the tortoise?

So, I think what normally happens, and this is the nerdy gerontologist term for this, it's called rectangularization of the morbidity curve.

So, what the hell does that mean?

What that means is that most of us experience this sort of gradual decline as we get older.

And that means that our faculties go away, we become more frail, and all this kind of thing.

Whereas these animals that are negligibly senescent, and by the way, it's not just these negligibly senescent animals, actually, humans who make it to the age of 100 have a very similar phenomenon.

What you find is that their period of morbidity, it's that period of illness and frailty at the end of life, is just squashed right down.

And that's such a

great aspiration, basically, for us.

Wouldn't we rather all just fall off a cliff, have a heart attack out of nowhere, basically, having been playing football with your grandkids the previous day?

It's interesting because it's not just wearing out, is it?

Because of course, our bodies are perfectly capable of regenerating.

So it is more complicated because as you said, you just think, well, the heart's been going for 170 years, maybe it just breaks.

Yeah.

But of course, you can regenerate things.

We regrow fingernails, for example.

So, what do we know about the reason?

What is the reason that, from an evolutionary perspective, maybe, what is the reason that

all things age, pretty much, all living things?

I think the

aging actually happening is accumulation of damage, failure to repair.

One of the things that I think people are terribly interested in at the moment, because it looks as though we might be able to intervene, is things called senescent cells.

So, normally, during development, or if we have a wound, there's a healing process or a tissue remodelling process during development.

And there are senescent cells that come along and do the remodelling.

And these cells have spit out lots of very active biomolecules to do the remodelling of the tissue.

And normally, in a healthy situation, the immune system will come along and remove them.

But that goes wrong during aging, and they accumulate in tissues.

And they actually cause a lot of problems there.

And there's very strong evidence now that if you remove them, so the most recent paper I've seen on this, somebody's actually produced a vaccine that you can inject into a mouse and it removes these cells.

And you get much healthier tissues, and the mouse lives longer.

So all of these sorts of things that go wrong, yes, it's a slightly baleful list of things that aren't repaired sufficiently, but they're also potential targets for intervention in our own health during aging.

The thing to me, though, is given that it is fixable potentially, then the question of why we haven't,

why the body doesn't fix it naturally comes up.

I mean, there must be an advantage.

I think the answer to your question is that we're like laboratory animals, or like animals in zoo, or like Lonesome George in the Galapagos.

We're all living way beyond the ages that we used to live in our evolutionary past.

We're in a highly protected environment, good food, clean water,

very

well-controlled range of temperatures and physical conditions, immunization, antibiotics, all the benefits of modern medicine.

And so we're hugely outliving the probably maximum 35, 40 years of our evolutionary past.

And natural selection simply hasn't had the chance to fix the things that happen in a 60-year-old or a 70-year-old or an 80-year-old because it's just never seen them in the past.

Nobody lived that long.

So I think that's what we're looking at.

It Must have been so weird when

people first saw people living beyond 40 and 45.

Like in villages and stuff, like when they saw the first 50 year old, they must have just gone, what is wrong with that poor, poor person?

But what a shocking thing to not have an explanation as to why they looked so dreadful.

Because everybody else would have been like 20 and Nubile and just going, oh, that is really tragic.

What's that guy?

What's he done to himself?

That would have been a financial thing, though, won't it?

That will have been like, you know, the P.T.

Barnum thing.

Come see the 49-year-old man.

People throwing up.

Statistically, so if we go back through history, so when do we start seeing that shift from the

30, 35, 40?

How did that change over the last few centuries?

What's really remarkable is how constant it's been throughout human history.

I think if we like teleported ourselves back to 100,000 years ago.

He says you can't.

Just so you know.

If you're currently dealing with if that's going to be some of your research for the next paper, they will not fund it.

It's not me, it's the laws of nature.

It's the geometry of space-time.

Anyway, we don't need to go there.

So if you were to teleport yourself back 100,000 years.

Which you can't, but.

Time travel terms and conditions may apply.

Is a bunch of human beings hunting and gathering, you know, around in the savannah in Africa or wherever it was.

They wouldn't be human beings, of course, they'd be a slight precursor species.

But they probably lived to 30 or 40 years old as well.

And

what this life expectancy actually masks is it masks a couple of things.

Firstly it masks the terrible toll of infant mortality.

So back in those days you only had about a 50-50 chance of making your 20th birthday.

But if you did luckily enough, you know, make it to that age, there probably were a few 50 and 60 year olds actually wandering around.

Not old by modern standards, but old by those prehistoric standards.

And actually that remained almost identical until the early 1800s.

So if you were moving into a fast industrialized town or city in the UK, back in those days, obviously there'd be less saber-toothed cat maulings and more factory accidents or something like like that, and different infectious diseases that were more at home in these sort of densely populated urban areas rather than out on the savannah.

But actually, life expectancy then was very high infant mortality, some people sort of struggling on into their 60s and perhaps, and therefore 30 or 40 on average.

But then, what's absolutely remarkable is if you look at the top performing country in the world at any given time, and you follow that line for about the last 200 years, every single year, three months has been added to life expectancy.

So, we've gone from sort of 3540 to about 84.5, I think, is the current record, which is Japan at the moment.

And it's just actually almost suspicious that this line is so straight, even though it's been underpinned by this tangle of socio-economic changes.

You know, first of all, it was stuff like hygiene and improving public health in towns.

Then, of course, we understood things about antibiotics and vaccines and that kind of stuff, which happened in the early 20th century.

And it's only by about the 1950s that we really started to make advances in the life expectancy of older people.

So, I was absolutely astonished when I was doing research for the book, like how recent a lot of the innovations in cardiac care are, for example.

CPR, which is absolute cliché, cliché.

This is the thing where people do chest compressions on the TV.

You see that on every medical TV show, every, you know, loads of films, was invented in the 1960s.

So if someone, you know, on television for a show.

We should try this out in real life.

No, it'll never work, Dr.

Kildare.

So is the reason for that

death was usually statistically it came externally.

So there's just a pretty much constant chance of dying

most of the way through your life.

Yeah, but how can we make that transition into it actually being internal and biological.

That's exactly right.

And I think there's a psychological element to this.

So

if you go back to the 1930s, there's this phenomenon called calorie restriction where you can massively reduce the amount that an animal eats and you can extend its healthy lifestyle.

Amazing results.

And this was first shown in 1935 by a scientist called Clive Mackay.

And he showed these rats lived like half as long again as their compatriots who were eating what they liked just by cutting back in their diet.

And yet, that research more or less lay fallow for about the next half century.

And I think the the reason for that was what Mackay was really fascinated by.

This was the period in history when we were just discovering vitamins and nutrition was getting a lot better and that kind of thing.

And what that meant was he was really fascinated by the sort of developmental side of things.

He was fascinated by the fact that these rats that were fed so much less, they grew to a much smaller eventual body size.

But he wasn't really, you know, although the life extension was sort of interesting, it wasn't really the primary focus of the research.

Because, you know, this is a time when childhood nutrition was a huge, huge topic.

And it's only, as you say, you know, when you get later and later into the century, people are starting to live to 50, 60, 70, 80 years old, that people start thinking, hang on, maybe we should do something about all this terrible stuff that happens when you get there.

Oh, Sarah, before we came on, you said that you were

the intermittent fasting idea.

Yeah,

I love it.

And I feel it's been a really good way to just not have to think about,

to just keep my weight down in a sort of healthy way.

Like, I eat what I want for the hours that I'm eating, but just kind of going, as of six, I'm just not, I'm not having anything until 10 a.m.

And it just feels like it really fits in with my body's natural kind of rhythm.

Like, I don't need to be stocking up on calories in the evening.

I'm sure there's no evolutionary reason to be, you know, guzzling Ben and Jerry's at 9 p.m.

It's just been a really easy way for me to not have to think about it too much.

But it feels right.

It feels sort of.

Yeah.

It really comes out of the whole dietary restriction story.

Because now that people have started to go into it really carefully, it's not just calories.

It matters what nutrients you actually take out of the diet for the experimental animal studies, if you're doing rats or mice or flies or worms, then actually it turns out the protein is really key to a lot of it.

You really want to have the right amount of protein in your diet because we've all got a target for how much protein intake we want to have.

And if there's too little protein in the diet, then people and mice will keep eating until they get the amount of protein that they want.

That means they overeat all the rest of it.

If, on the other hand, there's too much protein in the diet, then that's a risk basically for cancer.

It increases circulating, it's called insulin-like growth factor, which is itself a risk factor for cancer.

So it's really important to keep it intermediate.

But it turns out that a lot of the dietary response and these dietary restriction experiments to do with protein.

Then another thing about them is that the way that they're actually done is that the animals that can eat what they like just have food all the time and they eat what they want.

Whereas the restricted ones ones are given a fixed proportion, you know, 60%, 50% of what the other guys are getting.

And so they're handed that at a particular time of day.

And typically, they just scoff the lot straight away because they're really hungry.

So, of course, that means they're fasting for the rest of the day.

So, there's a huge intermittent fast in that group.

And the other thing that seems to matter quite a lot is when they're given it.

So, it's a really bad idea to start eating a large meal in the middle of the subjective night.

It should be at the beginning of the active period that the food's given, your time of day point.

And of course, mice are nocturnal, and typically in a laboratory situation, they get that food when the care people come in to look after the mice, which is first thing in the night of the mouse, which is not ideal.

But all of these different things, it's a much more complicated intervention than you'd think.

And people are picking apart these different aspects of it and trying to decide which are the really important ones.

And might we, in humans, be able to come up with dietary regimes that people can actually do?

Because most people don't have the willpower to do genuine dietary restriction.

It's been tried in a clinical trial, and it was extremely difficult to get subjects, and there was very low compliance with the regime.

So, I'm afraid we, as a species, are not great on that kind of willpower.

But there may be other kinds of interventions that we can do with food that would capture some of the benefits.

Getting back to the theme of the show, why I look so ancient

In my 20s I would very often start the day after living a bad life the night before by eating a custard donut and drinking a bottle of chocolate milk.

Could that be why I look so ancient?

Sarah.

Look, Robin, I have absolutely no expertise in this area, but I think you bang on the money there.

That that's why you look like some sort of like Benjamin Button style thing happening with your aging process.

No, he's definitely getting older.

He's a soldier.

I think so.

Very fast.

I wanted to ask you, Andrew, whether, you know, you hear it said sometimes, but it's in the genes.

So it's something to do with the gene.

Is there any evidence that you are born with the kind of with the Robin's constitution, let's say,

that you will look

older than your years?

Or is it lifestyle, as Robin alluded to, or is it something else?

So there's clearly a genetic basis to longevity because mice live three or four years, humans live 70.

And what's the primary difference between us is our DNA.

No, I know he's genetically different to a mouse.

Exactly.

So,

it's one of those episodes of who do you think you are, and I was quite surprised to find out my grandmother was a finger bob.

Assuming Robin does come from the genus Homo, then actually, what we find is that within human beings, if your parents live to a fairly normal age, like anyway, between 60 and 85, say, there isn't a huge genetic component.

So, there's a bit of controversy depending on exactly how you use the the statistics that you do in the studies.

But something like between five and twenty percent of how long you live is determined by your genes, and that means somewhere between eighty and ninety-five percent is down to lifestyle and is down to luck.

And obviously, luck you can't do anything about, but lifestyle can therefore have quite a large influence.

The real difference comes if you have parents or siblings who made it to an incredibly old age, so if they made it into their 90s or even into their hundreds, we know that if you've got a parent or a sibling who made it over the age of 100, you've got a 10 times greater chance than the general population of doing it yourself.

So, clearly, at these extreme ages, people have some kind of protective genetics that allows them.

In fact, if you talk to these centenarians or even the super centenarians who make it to the age of over 110, they often smoke about as much as the general population.

They're about as overweight as the rest of us are.

They don't do any more exercise, or there's no secret formula.

It just seems that they've got some almost magical combination of genes.

That's another great thing we can mine to try and understand what it is that they're not doing, whatever it is that's going on in their genetics that we could hopefully transfer to the rest of us.

Oh, I so hope the DC franchise makes a movie of the super centenarian.

I think that's got a lot of possibilities.

Didn't I read a piece in your book that the statistics are difficult for people over 100 because there's a great deal of pension fraud that goes on.

So people misreport.

It's incredible.

Yeah, there's this idea of the blue zone, which is these parts of the world which have these, you know, these sort of wonderful, ascetic, old-school diets and lifestyles.

It's all about the community and the low-level exercise they get throughout the day.

But there's a fantastic bit of research that came out of the University of Oxford a couple of years ago by a guy called Saul Newman.

And what he found was: so, let's take the example of Okinawa, which is this beautiful tropical island just off the south coast of Japan.

It's got supposedly the highest rate of centenarians in the whole country.

But when you drill, and

why are those centenarians so you know making it to that age?

Well, it's because they eat this wonderful diet of these beautiful purple sweet potatoes that are only available in that part of the world.

So, what he actually did was he looked at the demographic statistics and he found that far from being the highest consumers of sweet potato in Japan, they're actually the largest consumers of spam,

which is probably down to the presence of a large US military base on the island.

And they've also got the highest prevalence of smoking, the highest levels of poverty.

You know, these things are all linked together.

And so the theory is that this isn't somewhere that's got particularly, you know, hasn't got an Office for National Statistics collecting detailed data.

So maybe if your mum dies, then you might on, you know, carry on collecting her pension in your name.

And so you get these people reaching these seemingly incredibly advanced ages on their diet of spam.

And you know, we've got this, this

the strange thing about it is a lot of the sort of Blue Zones advice is broadly correct.

Like it is good to to have a sense of community.

It is good to have sort of low-level, moderate exercise throughout the day.

It probably is good to eat that lovely purple sweet potato.

But actually, you know, the reality is these places aren't as magical as they seem because, as you say, pension fraud.

I just love that idea.

The idea of eating spam fritters and smoking 20 a day and going, I'm 133.

I hate what I eat and I wheeze a lot, but I'm going to keep on going.

I mean, spam's just had a very bad rap in the last sort of 20 years, hasn't it, anyway, in general, because of email.

Go to the Jars Brandreth corner.

Sarah, are you one of those people?

Because I always love those images that we have.

It normally seems to be an elderly French woman who's about 107 and she'll be telling different stories about the time she met Picasso and how she used to pick flowers with Franz Kafka and whatever.

And would you like to be one of those, you know, those kind of wonderful ancient women who just says, and I have a brandy every morning?

No, I mean, all four of my grandparents lived over 90

and they were the most depressing humans I've ever met in my life.

I'm not kidding.

I'm not kidding.

I mean, my to two of them how do I say yeah one my grandmother and my grandfather I mean they'd been married for 65 years and they just wished death on each other at every

yeah I mean you got to do you got to in order to live that amount of time and do it properly you need to strategize you need great intelligence.

You can't just let 107 years unfold and nail it.

Like, you've got to really put a lot of thought into that.

And I don't think my grandparents ever thought that they were going to live that long.

I think that that was a real shock to them.

They'd all lost their parents, sort of in their 50s and 60s.

You know, they'd had heart attacks, or they'd had, you know, and medical science had just improved so much for that post-war generation.

So they never knew that they were going to live that long, and they just didn't really plan for anything to.

I mean, I don't know how you plan 95 years.

It's a lot.

But no, I have no wish to live that long.

It's interesting.

There's two parts to this discussion.

There's how your quality of life can be maintained up to the age of 80, 90, 100.

And also, I suppose the limit, which is two questions, I suppose.

So maybe the limit first.

So, what's the oldest human?

Was it 122?

Oh, wow, there's a lot of discussion about her along the pension lines, really.

I love this so much.

So, she was called

the whole Guinness Book of Records turns out to be difficult to do.

Pension forms of pension fraud.

Even the one involving lying in a bath of baked beans for five years.

That's what you said so though, isn't it?

It is.

It's someone at the age of 60 going, I'll just pretend that

I'm 70 and just whatever.

And then actually, they then live for another 30 years.

It gets more and more complex.

Yeah.

Well, the rumour about this one is that she was, in fact, her daughter.

She was supposed to have lived to 122 and a half French lady, Jean-Louise Carmont.

But

it's gone backwards and forwards, this one, amongst the demographers.

But I think current opinion is swinging to the idea that she died, that they didn't tell anyone, they buried her, and her daughter pretended to be her.

Can't we carbon date her?

I've been thinking about that, whether we couldn't DNA her at least.

Yeah, I can't believe her.

Yeah, look at the pedigree, but anyway, don't let's go there.

So is there a

limit, do you think, to

human lifespan?

I mean, clearly there is now, it's of order of 100 or so.

But could you imagine with medical technology, can you go to 120, 130, 150, 200, 250, 300?

Is there a limit somewhere, do we think?

I don't think we know.

We've got no idea what medical interventions are going to come in.

I mean, already

there's a very strong precedent for taking preventative drugs starting in middle age that's had a huge impact on average lifespan.

So statins, drugs that lower blood pressure.

I mean, neither of those conditions that are being treated are actually diseases.

They don't have disease codes.

But what these drugs do is to prevent people from getting cardiovascular disease.

I mean, if we could do the same for cancer and neurodegeneration, we'd be looking at much longer lives.

And is that neurodegeneration, is that in any way possible?

What do we know about the the causes?

Because that's one of the things we're beginning to see now, isn't it?

As we get an aging population, that's clearly one of the big problems.

Well, at the moment, it I mean that whole class of diseases, so you know Alzheimer's, Parkinson's, Huntingdon's, that they're turning out to be the most intractable for treatment.

And also, because we're all living longer, actually, the age-specific instance of Alzheimer's has gone down because quite a lot of it was attributable itself to cardiovascular disease, which has been prevented.

But that's been counteracted by the fact that we're living longer, so we're seeing more of it just because there's an older population.

And by the time any of those diseases become apparent, it's pretty late to treat them because there's been quite a lot of loss of neurons, and neurons don't divide and regenerate, or their stem cells don't.

And so they're a difficult group of diseases.

But we know a lot about what goes wrong in those neurons, in those diseases, and it's our old friends, the basic mechanisms of the aging process, because of course it's the main risk factor for all of them.

And I can imagine a situation in which basically what you have to do is fix the way those cells handle their their proteins.

So, if you increase the quality control of the proteins in the nerve cells, particularly in the brain, also motor neurons, then we would be able to prevent those diseases.

And I can imagine we might be able to do that.

Andrew, I mean, your book is looking at some of the solutions.

How old would you like to live to?

Because I want to go to about 150, but I don't want anyone to disturb me.

I've got a huge number of books I haven't read yet.

That's kind of my, you know, when you get old enough to look at all your bookshelves and you go, oh no, I think I'll I'll die on the third bookshelf down.

You know, I want to get through all of those books.

How long do you want to live for?

Well, I think, you know, thinking about it in terms of books, by the time you've got to the bottom of those bookshelves, more are going to have been written, right?

Yeah, yeah.

So my thinking is, as long as I'm happy and healthy, I don't really have a hard limit on how long I'd like to live.

You know, as long as I'm healthy, as long as my friends and relatives are healthy, I think, in much the same way as there isn't a hard biological limit on how long we can live, I don't really think there's a hard social limit that I feel I need to conform to.

It's kind of fascinating.

I thought that

there was almost a programming,

programming to age and then death.

As you said, it maybe is helpful for the population that older people

are replaced by younger people.

But it seems to me the sense that you're saying now with the modern research is that that's not necessarily true.

There's not

a biological imperative that we don't appear to be able to get around in principle at least.

No, not at all.

And I think that those ideas that you're talking about: you know, old people should have the decency to die and get out of the way and create opportunities for the young.

No, I didn't say that.

I certainly did not say that.

Well, we've found the headline for the express.

Good because

I think that's kind of what you were hinting at.

You said that there was a sense that

biologically,

once you've reproduced, as you said, evolution doesn't care anymore about you.

I think natural selection does care very much.

Basically, the selection on individuals to keep reproducing is the strongest force of natural selection there is.

This idea that

you know aging could be adaptive, actually, in some groups, there's quite strong evidence now for grandmother effects, and particularly benefit on younger generations of having post-reproductive females around.

It's been particularly well worked out for killer whales.

So, what happens with them is that the old post-reproductive females lead the pod.

And what the demographics show is if those old females are lost from the group, it really depresses the survival of the younger whales.

And it seems to be mainly that they've just got this extraordinary memory of the range that that pod occupies and where they found fish and other things in the past, other sources of food, when there have been problems with the food supply.

So having somebody in your group with a really long memory is very useful if you're a killer whale.

I agree.

No, there's no fundamental biological limit, and I think it is just the accumulation.

I think the hallmarks are a really good way to think about it.

It's these various different processes.

It's no one thing, but it's just a variety of things that evolution just hasn't bothered to fix.

Because by the time you reach the age of 70, you're dead as far as evolution is concerned.

You've already had your kids.

Maybe you're able to provide some help as a grandmother.

But by and large, for a lot of animals in the animal kingdom, you're so long dead by the time you experience these age-related diseases.

I think mice are quite a good example.

Their lifespan in the wild is probably six to twelve months.

And in the lab, what mice die of, they tend to all get cancer about three years old.

But three years is just so much longer than a mouse would survive in the wild.

That why would evolution bother to fix that?

Sarah, what do you, again, now you're getting this terrible news for you that we might live forever?

And you've said that certainly you've seen genetically in your family, you're a very miserable family in old age.

The Kendalls don't know how to age well, but the thing that worries me most is what am I going to look like?

Like if I make it to 200, can you actually shut down the actual cosmetics?

Or will you, what's that going to look like?

I think the answer is if we can create 200-year-old humans, they're going to look great.

And the reason I think that is that all of these hallmarks of aging, they underpin not just the cancer, not just the dementia, not just the risk of death, not just the frailty, but also the cosmetic stuff.

Because, and you know, what this means is if we're going to keep people alive for longer, they're going to have to be healthy.

And because the same processes that make you unhealthy also give you grey hair, also give you skin wrinkles, then if we can fix the aging process itself, we can actually extend all aspects of youth.

It's an interesting because as we talk about these ideas and combating age and of course the other problem that we have which has kind of been mentioned as well which is you can only combat it so much because there are new generations coming along.

So do we need some kind of Logan's run system?

Not merely that people at 30 will be hunted down and killed, maybe older than that.

I was always accused of asking that when I asked a completely different.

So do you know what, Radio 4, there's always a bit near the end where we move towards eugenics.

So

this really surprises

a particular part of our demographic, the bit that reads the express.

I think this is a really fascinating question.

And the reason I think it's fascinating isn't the question itself, it's the fact that if we were doing a monkey cage on cancer research and we were all sat here talking about how these amazing new cancer therapies are going to help us cure pediatric leukemia, we wouldn't be facing these sort of enormous ethical questions of what we're going to do with all the people, what we're going to do if people can't navigate the world aged 150.

Even though fundamentally what those cancer researchers will be looking at is trying to give people longer, healthier lives.

But when you start talking about aging, we just seem to place it in a completely different moral, social, ethical category.

And you know, every interview I do, I'm asked about what we're going to do about population, what we're going to do if we get bored, what we're going to do about the immortal dictators.

And you just don't get that in any other field of science, even though fundamentally, what I want to demonstrate to you is that aging biology, it's just medicine.

It's just a pill you're going to take that's going to mean it'll prevent a range of different diseases at the same time, hopefully, so it's not just going to be a single disease medicine.

but fundamentally, it's the sort of the natural end point of all the ways we try and treat people these days.

I completely agree with that.

In fact, I I look at it the other way round, I think, you know, rather than the test whether you should be allowed to go to the next decade, I see it very much as a a a clinical medical thing.

I mean the burden of ill health in our societies now is is falling predominantly on the older section of the population, and we've always regarded it as an an imperative, an ethical imperative, in medicine to try and help people with their health.

And actually, I think the sort of people who do what Andrew and I do for their day jobs are actually much more interested in improving people's health up to the point where they eventually do depart this world rather than making them live longer.

It's fascinating talking about limits to human lifespan and the basic biology and what if.

I mean, that's the kind of inspiring conversation that one can have.

But the practical problem that we face is people getting sick as they get old.

And it's that I personally would like to fix at the moment, rather than thinking too much about making people live longer.

Although, of course, there is always the adage, you know, who wants to live to be a hundred?

Someone who's 99.

I think it would be a good thing if there was less death in the world.

And that is shockingly controversial in a lot of circles, even though I feel like it's one of the most basic human imperatives.

If we treat the underlying aging process, we have such a larger potential to increase human happiness.

And the reason is: not only will we prevent the cancer, not only will we prevent the heart disease, not only will we prevent the frailty, which is something that modern medicine does precious little to address because we're so laser-focused on treating those individual diseases, it'll even sort out the cosmetic stuff.

It'll mean that we're neurologically more agile, so we can sort out our emails in our 70s, 80s, and 90s.

So, given that all of those things are more likely to be preserved by targeting not the diseases, but the aging process that gives rise to those diseases, that's why I'm so excited about this stuff.

Sarah, so I'll ask you, as the non-scientist, do you you feel more optimistic or more pessimistic at the end of the show today?

Well, I mean, I hope it happens in my lifetime.

Is this going to happen in my lifetime?

Is my main question.

Yes.

That's the Woody Allen line, isn't it?

I hope that the secret to eternal life is discovered in my lifetime.

That's right.

So, do I get a piece of this delicious pie or not?

What's the prognosis?

I think you do, yeah, because

these senolytic treatments that kill the aged senescent cells, we've demonstrated they work in mice.

There are 20 or 30 companies now trying to turn these into something that works in the clinic.

And at first, these are going to be for specific diseases where we know that these cells are a problem.

But if they're effective, i.e., they kill the cells, they make the people with these diseases better.

And most importantly, if they're safe, because you've got to imagine, we're going to give these drugs to people who say they're age 60, they've accumulated enough senescent cells that it's time to clear them out and try and prevent some of these age-related diseases.

We want to be really, really sure these drugs don't have any side effects.

I'll take them.

That is,

you know, we're going to have the results of these clinical trials within the next five years.

If they work, and you know, if obviously, if we get a bit lucky, because that's how biology and biomedicine goes, we could easily be handing these things out for the first time in the next 10 years.

And there are loads more ideas on the drawing board.

We asked the audience a question as well.

We asked them, what were you most looking forward to as you age?

And our answers include: seems a funny question to ask a Rodeo 4 audience, already there.

As I am 90 years old.

So, Brian Davis, are you 90 years old?

You don't look a day over 60, I'm saying.

So you said, as I'm 90 years old, I'm looking forward to downloading myself so I can annoy my family for another 90 years.

Oh, downloading yourself.

That's a great.

The liberal use of incontinence wear as things can only get bed wetter.

Thank you very much to our panel, Andrew Steele, Dame Linda Partridge, and Sarah Kendall.

We are back next week, but before that, we're going to kind of continue this experiment.

And Brian and I are going to swap lives for a week.

So I am now going to just walk along a sunlit beach with almost unlimited expenses from the BBC while someone holds a parasol over me.

And then I'll eventually explain the retrograde motion of Mars.

And Brian's going to spend a week in my dark attic writing melancholy poetry about winter.

And

we're going to see if that brings on some form of aging with him anyway.

So thanks very much for listening.

Thank you to our panel.

Goodbye.

In the infinite monkey cage.

In the infinite monkey cage.

Feeling that nice again.

Hello, this is Marion Keys.

And this is Tara Flynn.

And we're here to remind you that our podcast, Now You're Asking, is back for a new series.

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