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Jan. 31, 2021 - The Unexplained - Howard Hughes
52:00
Edition 514 - Andrew Steele

UK-based Andrew Steele has done intensive scientific research into ageing - and how we might be able to overcome it - for his new book "Ageless"...

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Across the UK, across continental North America, and around the world on the internet, by webcast and by podcast, my name is Howard Hughes.
This is the Unexplained.
Thank you very much for all of your emails, your communications, all of the things that you've said, all duly respected and noted.
If you send me an email, don't forget, of course, to tell me who you are, where you are, and how you use this show.
And it's very nice that some of you have been doing that recently.
It's just good to hear your stories and the ways that you use this show.
And some people saying that this show during lockdown has helped to keep them going, which is nice.
It's funny, really.
It has the same effect, but in reverse, somewhat with me.
Doing the shows is probably what's stopping me climbing the walls at this period.
So they're as important to me as they are to you, it seems.
But thank you very much for the nice things you've said.
Always gratefully received guest suggestions, comments on the show, whatever you want to do.
Please go to the website, theunexplained.tv, follow the link for emails, and you can send me a communication from there.
And don't forget, of course, to fill in the subject line.
Some people don't do that, and then I don't know what's coming, so don't forget to fill in the subject line when you do that.
Thank you to Adam for his work on the website and getting the shows out to you.
And as ever, thank you to Haley for booking the online guests here on The Unexplained.
Now, what you're going to hear on this edition is somebody who is absolutely fascinating, I believe.
He was on my radio show recently, and I wanted you to hear a version of that conversation here also on the podcast.
It is worth keeping, I think this one.
His name is Andrew Steele.
He is a scientist, a broadcaster, and writer, and has confronted one of the things that I think all of us think about.
Maybe not in too much depth.
But we all confront these issues from time to time.
The issues of getting old and ultimately dying.
What if we didn't have to do that?
Or certainly not in the way that we currently do it?
What if we could live much healthier lives for very much longer?
Well, I'm going to get on that bus if it's coming my way.
There are ways being worked on at the moment where that might be possible, and Andrew Steele has looked into them in an entertaining but scientific way in his book Ageless.
So the guest on this edition of The Unexplained, Andrew Steele, I hope you enjoy it.
Please let me know on a subject very close to all of our hearts.
You know, I never talk about my age because I never let it affect me, really.
I never think that I'm whatever age I might be.
I always think that there are this number of things that I still want to do before I'm finished here.
And the list of things that I want to do and achieve and put right seems to get longer every year.
So if there was a way to extend it all, I would be very keen to do that.
You know, if there was a way to live a healthier and longer life, wouldn't we all want to buy into that?
Andrew Steele coming soon.
Don't forget, if you want to get in touch, go to the website, theunexplained.tv, follow the link and send me an email from there.
Always good to hear from you.
And, you know, your emails are keeping me going.
All right, let's get to just down the Thames Valley from where I am.
And Andrew Steele should be there.
We're going to talk about the process of aging and how it doesn't quite have to be like that.
Whenever I think about this topic, I always think about Morgan Freeman's character in the movie The Shawshank Redemption.
Ellis Redding, Red, wasn't it?
And he said at the end of the movie, words that I've never forgotten, get busy living or get busy dying.
Well, those words definitely speak to what we're going to talk about this hour.
Andrew Steele, thank you very much for listening to all of that and thank you for coming on my show.
Thank you for having me.
It's a pleasure.
I mean, it is, isn't it, a case of get busy living or get busy dying?
You know, we have to get on with this life, but every so often we're interrupted by thoughts of how finite it is.
Yeah, it's a strange thing because when I talk to people about this idea of, I like to talk about curing aging, which sounds like a really sort of jarring juxtaposition of those words, but it does make a lot of people think about, you know, these incredibly long lifespans, about, you know, all the different moral and psychological implications would be.
But actually, I think you're absolutely right that most of the time we live our lives day to day.
You know, we don't often stand back and think about, you know, our impending death or our impending degeneration due to age.
So it's a strange moment when we have those considerations.
And when you do, you know, it's quite a big existential challenge to get your head around it, isn't it?
And most, it is an existential challenge, but most of us tend to either dismiss the thought or keep the thought in mind, but just accept it.
Accept the fact that there is going to be an inevitable decline.
I think in the book, you start saying by the time you hit kind of 50, 60, that is the point at which maybe 65, that things begin to, you know, not work maybe as well as they did.
And then it's a complete lottery, maybe determined by your genes, maybe determined by other things, you know, as to what happens next.
Yeah.
And so the way that I try and quantify aging is a bit morbid is to look not just at sort of the frailty, the dysfunction, all this stuff that happens to our bodies.
It's to look at our risk of death.
And our risk of death as humans doubles about every seven or eight years.
And what that means is it starts out quite small.
So I'm in my 30s.
My risk of death every year is something like one in a thousand.
And if we just step back and think what that means, you know, if that were to continue for the rest of my life, I'd live into my thousand and thirties on average.
So clearly that isn't what happens.
But because this, you know, doubles every seven or eight years, not much happens for the first four, five, maybe even six decades of life.
But say by the time you're 65, your chance of not making your 66th birthday is about 1%.
And if you're lucky enough to make it into your 90s, your chance of not making your 93rd birthday, if you're 92, is about one in six.
That sort of survival at the roll of a dice.
So this exponential growth really means that you sort of chug along relatively fit, relatively healthy, pretty unlikely to die for an awfully long time.
And then suddenly in your 60s, 70s and 80s, it just comes all at once.
But in the midst of all that, there are those, and we'll get into all of that probably in the second part when we talk about the science in depth.
But in the midst of all of those thoughts and considerations are the news reports that we will get three or four times a year of somebody in France or Japan who's lived to 106 and 120.
And we all think, well, isn't that wonderful?
And how did they do that?
Yeah.
And what's really fascinating is that, you know, that's still an open question in science.
Is there some kind of upper limit to our current natural lifespan?
We think there's a significant genetic component to how these people live these incredibly long times.
Fascinatingly, genetics doesn't play so much of a role for most of us.
So, you know, if your parents made it to 70 or 80, you shouldn't really see that as sort of a ceiling on your lifespan.
We think that only about 10 or 20% of How long you live is determined by your genes.
And so that means that 80 or 90% of it is lifestyle and luck.
And obviously, luck you can't do much about, but lifestyle you can try and optimize with all the standard health tips.
And I talk about a few different ways you can try and do that in my book.
But if you want to make it to 100, you want to make it to 110, the best advice is choose your parents and your grandparents well, because it seems that the genetic differences really do drive these extreme long lifespans.
Historically, you do talk about this in the book.
And there are exceptions, of course.
But historically, how long did people live?
I'm thinking about the chapters and the paragraphs in your book where you talk about people in certain parts of our history living to perhaps only 20.
Yeah, so the life expectancies back in prehistory are probably hovering.
Obviously, it's hard to tell because we haven't got detailed demographic data about prehistoric people running around, but probably somewhere in the region of 30 years old.
And that sort of obscures as much as it reveals in some ways, because on the one hand, a huge driving factor behind that, if you imagine that's the average length of time that people lived, a huge driving factor behind keeping that so low was just that so many people died in childhood or in their teenage years from things like infectious diseases.
And that meant that there was only something like a 50-50 chance of you making your 20s, for example.
But if you did make it, you know, made out of your teens successfully, then you could probably expect to live another 30 or 40 years, which means that there were some prehistoric people living into their 50s, 60s, maybe even the lucky few got into their 70s.
So they did make it into what we would now call old age.
So this sort of headline figure about 30, 35 years, obscures the huge toll of infant mortality.
But it also blinds us to the fact that a few prehistoric people probably did make it to quite reasonable ages.
And we tend to pat ourselves on the back very fulsomely, don't we?
And say, look how well we're doing, you know, the advancements in modern living.
People lead cleaner lives.
They get medical assistance.
There are so many things on our side.
So look how long we're living now.
And if you compare that to people in history, we're not doing so well.
But we have to remember that in history, people had things that we didn't have to contend with as much as we have to now.
And of course, we're in the middle of a pandemic.
So, you know, we have a plague of sorts at the moment.
But, you know, in those eras, they were regular occurrences.
There were plagues, pestilence, wars, things that wiped people out en masse.
So of course, a lot of people didn't survive.
Yeah, and I think this pandemic's a real reminder of how challenging it can be to deal with an infectious disease to which there isn't some level of immunity in the population, to which we don't have a vaccine.
You know, we're just starting to develop the first tentative treatments.
It's really sort of thrown us back into a previous time in terms of our understanding of, you know, how we cope with all this stuff.
Because, you know, over the course of human history, probably the leading killer has basically been infections of various different kinds.
There were wars.
There were, you know, there was interpersonal violence.
There were, you know, you could get eaten by a saber-toothed cat.
But I think those are the exception rather than the rule.
And a huge, huge number of people were felled by infection.
But nowadays, of course, we've got vaccines, we've got antibiotics.
And that means that for those of us lucky enough to live in the rich world, at least, there's relatively little death from infectious disease.
But what's interesting is that aging even manages to sort of inveigle its way into that as well, because it's not that we've entirely prevented infectious disease.
To a large extent, we've deferred it.
By far, the majority of people who die from infections are over the age of 60.
And so what that means is, you know, it's because our immune systems decline, because of all these, you know, changes in our biology that I'm sure we're going to go on to talk about that just make old people that much more susceptible.
And that's another thing that coronavirus has really underlined.
I think you're hundreds of times more likely to die of coronavirus if you're in your 80s than you are if you're in your 20s.
So it just really shows us, you know, this is the power of infectious disease.
And it's something that we've, you know, maybe taken our eye off the ball because we've got a bit complacent about.
Yeah, most people didn't think about these things.
And, you know, to their discredit, governments around the world weren't thinking about these things either.
But the fact of the matter is that as you get older, your susceptibility to things that come along is greater.
And we didn't really, nothing in the modern world, and I'm talking about this first world that we live in, prepared us for that.
You know, we've, we've kind of bought the model on TV.
And the model on TV is that, you know, you should live a jolly happy life and, you know, probably have a super pension at the end of it all and live in great conditions.
And that's what you can expect.
So the fact that coronavirus came around and exposed difficulties that are there because of the way that we're made up, it is affecting very, very sadly people, you know, 60, 70 and upwards, you know, mostly those in their late 70s, 80s are the ones who are very much in the firing line.
That's not something that should be a surprise, but it has been.
Yeah, I think that's exactly right, because I think, you know, a lot of the way that we deal with aging, a lot of the way that we deal with diseases in general, is really pushed out of sight, out of mind in the modern world.
A lot of this stuff happens behind closed doors.
It happens in hospitals.
It happens in care homes.
If you look at the statistics, the average age of somebody caring for someone else over the age of 65 is 63.
And what that really means is, you know, it's going to be partners caring for their partners.
It's going to be kids caring for their parents.
And if you take the example of someone in my generation, again, someone in their 30s, it's so easy to be completely insulated from this stuff because my parents are looking after their parents, but I'm, you know, largely not involved.
And it's so easy just to go through, you know, four, five, maybe even six decades of life without properly engaging with the, you know, the state of aging and what the coronavirus pandemic has done.
It's an acute problem rather than a chronic one.
It's not something that we can just hide behind closed doors because it's affecting us all the time.
It's in the news every single day.
And I think it's really shown us the toll that aging takes on our physiology and, of course, the huge sort of moral, social toll that can take as well.
But we've been conditioned to think that that's the way that it is.
If we've considered this at all, then we've tended to think, well, you know, your average person gets three score years and 10 is what they used to say.
Well, you know, that's 70.
And these days, I read obituaries of people who die at like 68 and they say, died tragically young.
You know, three score years and 10 doesn't cut it anymore, does it?
It's really interesting, actually, how we've sort of exactly internalized this idea of long life, even though it's a relatively modern innovation.
So we've been adding, on average, three months of life expectancy per year, every year, since about the middle of the 19th century.
It's been this incredible clockwork increase, even though it's been driven by a hugely disparate range of different factors.
That's been happening continuously over that time.
And what's bizarre is that, you know, we look around the modern world and we just think that's what we're allotted.
That's our right almost.
But I think a really striking example of this is the pension age.
So the age at Which men receive their pension was first set in the 1920s, and it was set at age 65.
And there are various, you know, bits that have been twiddled, policies that have been changed, but ultimately, that pensionable age for men didn't change until 2019.
And in that intervening almost a century, you know, life expectancy in the UK was absolutely transformed.
When that was first introduced, there were a handful of people making it to 65.
They were probably pretty sick.
They were going to claim their pension for a few years because they basically physically couldn't work anymore.
Whereas now, if you hit 65 and start claiming your pension, you can probably expect to live for another 20 years.
You might get 10 or 15 of those in reasonable health.
So somehow we've managed to completely ignore this huge demographic change and ended up with what is quite unsurprisingly now one of the single largest items of government expenditure.
And yet, we consider it our God-given right to have a lovely long retirement with plenty of cash.
So it's really fascinating how attitude to this.
Yeah, we just sort of accept everything as though we should be handed it on a plate.
And actually, history shows it's more complicated than that.
I'm not asking you for an explanation of this, but you might have one.
It seemed to me that when I was a kid, older people looked like older people.
You know, my dear grandmother, when she got to, probably when she got, I first came into this world when she was my age now.
And I always kind of thought of her and she dressed older.
I thought of her as older.
And she continued to be older.
And she, you know, she lived in that frame, had that appearance, dressed in that way until it was all over for her.
You know, wonderful, wonderful person.
But it seemed to me, the point that I'm getting to is that it seemed that people accepted, that's it.
They accepted older age much earlier than we do.
I think that's actually borne out in some of the statistics.
So there was a fantastic study in 2009.
I say fantastic.
It's actually slightly morbid.
What they did was they got people to look at photographs of older people and guess their age, basically.
And they got these panels of assessors to guess how old they were.
And what they found was that how old they looked was actually a predictor of how long they had left to live and how soon they'd get certain diseases over and above their chronological age.
So, you know, the age on their birth certificate, effectively, number of candles on their birthday cake.
And that's just really fascinating because what it shows us is that how old we look on the outside is to some extent an indication of the sort of equivalent of wrinkles and grey hair going on inside our bodies that are causing these diseases that are causing frailty.
And what's fascinating is that although we haven't yet got any medications that directly tackle the aging process, and obviously that's what my book's about, nonetheless, through various different means, through improvements in lifestyle, through reductions in infectious disease, through this whole combination of changes in society, it does seem that we have actually pushed back aging.
People are aging later.
They're living healthier.
They're living longer.
So I think there's definitely some truth in that.
I think as I was saying before, people who are 65 when the pension age was first introduced were looking haggard, wrinkled, grey-haired, incredibly frail.
Whereas now you can be relatively fit at that age and have quite a lot of retirement to look forward to.
Do you think some of it is the way that we condition ourselves?
I sometimes, I don't, my colleagues will tell you, I never discuss my age.
I'm almost superstitious about it.
I just don't tell people.
You know, it's none of their business.
It doesn't affect anything to do with the way that I function.
I function probably better professionally now than I did, say, 20 years ago.
I don't know whether that, what kind of judgment that is on how I was functioning 20 years ago.
But, you know, I just don't refer.
I don't go there.
It's not a factor.
I wonder if there is a little bit, before we get into the science in the next segment of our conversation here, I wonder if there's a bit of psychology here.
I think so.
And what I want is a world where, you know, you're the paradigmatic example.
I want us to have a world in which how long ago you were born is as irrelevant as we can possibly make it.
I don't want old people to be frail.
I don't want them to be forgetful.
You know, I don't want them to be losing their independence, losing their eyesight, losing their hearing, less able to function in society.
And the fact is, you know, we do accumulate wisdom.
We do, you know, we can be better at our jobs as we get more and more experience.
So, you know, growing old isn't all a bad thing.
But if we can take away the physiological and the psychological negative changes that are happening because of the changes in our biology and make our age, you know, just a sort of piece of trivia, then that's what I'd like to see in the future.
But it is still very variable.
You know, I know somebody not far from where I live.
She is remarkable.
You know, you never give away a lady's age, but nobody believes that she is.
In fact, I know two people in this situation.
And they both go to the doctor or they go to the hairdresser.
And every time they go, the doctor or the hairdresser says, I can't, you know, they have to look at the paper again.
I can't believe you're this age.
And I think part of it is, maybe they've got good genes, but part of it is their mindset too.
Because the two people I'm thinking of, both of them don't think older.
I don't think older.
And maybe that is, as you say, part of the mindset that if you refuse to make it a factor, and if society refuses to make it a factor, and if society is backed up by medical advances, science, and getting to grips with this problem, then it won't be a factor.
And that, I think, is what's fascinating about your work.
In medicine, there's something, a lot of people have heard of the placebo effect, which is this idea that you can give someone a drug or you can give them a sugar pill that contains no active ingredient.
And often people will report, they'll report they'll get improvements in whatever condition this drug is supposed to treat, even if they're just taking the placebo sugar pill.
There's a counterpart to that, which is less well known, called the nocebo effect, which is that if you give someone a sugar pill, they often report terrible side effects because again, a lot of this is in the mind.
And without wishing to diminish all of the huge suffering that people with age-related diseases can be going through, the loss of independence, the loss of strength, the inability to get around and do what they want to do, I think there's definitely an aspect to which mindset can play into this because everything we know about medicine tells you that attitude does certainly play into real physiological outcomes.
And Andrew, I've got how many pages of notes have I got here?
Six pages of notes here on the book.
You go into the science of this.
But before you do that, I want to just, if it's okay with you, read a little bit from the introduction to your book.
Is this okay?
Absolutely.
Go for it.
Okay.
Wrinkled, toothless, and ambling with a ponderous gait.
It seems unlikely at first glance that the giant Galapagos tortoise could teach us anything about aging gracefully.
They're eponymous inhabitants of the remote Galapagos Islands, a volcanic archipelago in the Pacific which draws its name from the old Spanish word galapago, meaning tortoise.
These cumbersome reptiles can weigh more than 400 kilograms and take decades to reach maturity on a diet of leaves and lichen.
Now that's a lovely description, And I'd never thought about that before.
But you go on to say that part of it is to do with the pace at which they live.
One of the big factors relating to how you age, it can be indeed sort of the speed of the chemical reactions that are going on inside your cells.
So, some of the aspects of why we age are basically damage that are caused by things like overexcitable, basically, very, very reactive molecules.
Because if you think about how we make our energy, what we've got is things like sugar, things like oxygen buzzing around inside our cells.
The reason that they're able to power a human is because they're very, very reactive chemicals.
And so they can go on to do damage to the workings of the inside of your cells, the molecules, everything that keeps your body ticking over.
And so there's a school of thought that just by living more slowly, like a cold-blooded animal like a Galapagos tortoise, you can by implication, just live longer.
Now, actually, what's going on inside tortoises is a bit more complicated and more interesting than that, because if they just live longer, they can live perhaps up to 200 years, a Galapagos tortoise.
And if that was just because they were living more slowly, that wouldn't be very biologically interesting.
But what's really fascinating about them is I mentioned in the first part that humans, we have a risk of death that doubles about every seven or eight years.
A Galapagos tortoise doesn't have a risk of death that doubles at all.
It stays constant no matter how old it is.
So it's not just that the candle that burns half as bright burns twice as long.
It's also that they don't seem to age in a very fundamental biological sense.
You talk later in the book about whales.
And of course, whales can live to ripe old ages too.
And you say, if you're a whale, the monarch of the oceans, and subject to few natural threats, you can afford to chill out, mature more sedately, and have children at a leisurely pace.
This pushes back the date at which it's evolutionarily acceptable to die at the hands of accumulated mutations or genes.
In other words, although a lot of this is science, some of it is to do with the conditions in which you live.
That's exactly right.
And I think it's important to say it's the conditions in which you live over evolutionary time.
So although obviously your environment can have a huge effect on your health and your rate of aging generally as a human, what's happened to whales is that over millions and millions of years, you know, generations and generations of creatures living under the sea, what's happened is whales have got into a situation where they're big, where they can escape predators.
And therefore, that means that they aren't dying of a lot of the things that might kill smaller animals.
And that means they can, exactly as that quote from the book says, you know, afford to take their time.
And that means that they can afford to devote some of the energy they might have had to put into reproducing quickly and, you know, getting on with life as fast as possible into things like defenses against cancer.
So one of the most fascinating things about whales is that they're so, so much larger than humans.
And yet their cells are about the same size as human cells.
And the way that a cancer happens is basically one of your cells gets unlucky, accumulates a combination of changes that allow it to turn into a tumor.
So you might think that a whale living for 150 years and so, so much bigger than a human being, they might weigh 100 tons.
Surely it's going to be absolutely riddled with cancer because it's just got so many cells, so many chances for that cancer to arise.
But because it's over evolutionary time managed to accumulate all these changes that allow it to live longer, it's built itself really robust anti-cancer defenses.
And so by looking at these animals all around the animal kingdom that have worked out how to outwit diseases and even outwit aging, maybe we can apply some of those lessons to our own biology.
So the whale over time has thought in evolutionary terms, I've got a ton of time here.
Let's give some of that time to fending off the effects of cancer.
Exactly.
And I think the sort of paradox about the reason that aging evolved is that the reason it evolves is because you can be killed fundamentally by other things.
So imagine at the other end of the scale, imagine you're a mouse scurrying around, you know, trying to make your living.
We talk about evolution being the survival of the fittest.
But what it really means is it's the reproduction of the fittest because, you know, it's no point surviving if you don't pass on your genes, if you don't have, you know, the next generation to carry on after you're gone, no matter how long you survive for.
So imagine you're a tiny mouse.
You've got cats trying to catch you.
You've got infectious disease.
A lot of mice actually just die of exposure because they're so tiny.
They've got little tiny bodies.
They can just get so cold that they just die that way.
So they've got a, you know, they've got a ticking time bomb, basically.
They're going to be killed in some way relatively rapidly, you know, maybe even in less than a year in the wild.
That means they've got to rapidly, rapidly, you know, spool up, have kids, get those children out into the world in order to pass on their genes to the next generation.
And that means they put much less energy into things like anti-cancer defenses because there's no point as a mouse, you know, having some perfect pristine cells that don't become cancerous at the age of three if you've already been eaten by a cat at six months.
So how could we build some of that into the way that we live?
The way that I break it down in the book is to look at 10 so-called hallmarks of the aging process.
And these are the fundamental cellular, molecular, and biological drivers of the aging process.
They're things that we notice accumulate as animals get older.
And they're also behind a whole range of different diseases.
So the problem is in the way that we currently practice medicine, we think about cancer as one problem and heart disease as another and dementia as a problem that's separate again.
But actually, if you delve into the biology, and this applies across a whole range of animals, of cells all around the kingdom of life, what you see is there are these common patterns, these common underlying causes.
And so the idea is that if we can come up with treatments that can target these so-called hallmarks of aging, we could potentially defer or even prevent loads of age-related changes simultaneously.
This isn't just the diseases, although that's sort of what I get excited about because these are the causes of suffering.
They're the biggest killers.
They can drag out your death over years or decades in the modern world.
It's actually behind all of these changes as we age.
It's behind the frailty.
It's behind the incontinence.
It's behind the loss of eyesight.
It's behind the wrinkles and grey hair.
So fundamentally, by tackling these hallmarks of aging, we can make you biologically younger is the hope.
And you say, actually, this isn't as insurmountable as it might sound.
The fact you say in the book that there are 10 is actually great news because you would have thought there'd be hundreds, maybe thousands.
But no, there are 10 things that stand in our way.
That's right.
And, you know, because if you think about, let's take cancer as an example.
There are hundreds of types of cancer because they can occur in any organ in your body.
And we know there are so many different subtypes of cancer.
Breast cancer isn't one thing.
There are loads and loads of different types of breast cancer depending on the particular genes that get mutated in your, you know, basically your personal tumor.
You know, it can be as individual as a single person.
And therefore, if we're going to come up with a way to cure cancer, we're going to have to actually cure hundreds and hundreds of different diseases and be incredibly clever about doing so.
But these hallmarks of aging, as you say, there are just 10.
And that's not to say it's going to be a cinch and we're going to have aging cured in five years' time.
But it does mean that we're tackling a much smaller problem than we are by going after these individual diseases that happen at the end of the process.
One of the things that stands against us is our DNA replication, isn't it?
You know, we're constantly renewing ourselves.
But sometimes, like if you were, I don't know, like people who used to photocopy banknotes, which you shouldn't do, on old-style photocopiers, by the time you get to the last one, it's possible that the image might be getting blurry.
And that's a really bad analogy, but that's kind of what happens with us, isn't it?
When your cells divide, evolution seems absolutely mind-blowingly stupid at times.
There's this saying in biology that evolution is cleverer than you are, but occasionally it's clever in some really quite roundabout and strange ways.
So if you look at your DNA, every time your cells divide, that DNA is the instruction manual inside your cells.
That means that instruction manual needs to be duplicated so that both of the daughter cells have a copy.
But our DNA replication machinery, evolution has designed it such that it can't quite make it all the way to the end of a DNA molecule.
And even after all these billions of years of cellular evolution, that's just the compromise it's gone for.
So the problem would be that if it was lopping off the end of your DNA every time a cell divided, then you'd end up in a situation where you were losing vital parts of this DNA instruction manual.
So what evolution has done, rather than fix the copying enzyme, is to add a piece called a telomere, an extended section of basically repeated nonsense onto the edge, onto the end, sorry, of each of your chromosomes.
And that means that when your cells do divide, you do chop a little bit of DNA off at the end, but it's some of this irrelevant telomere, so it doesn't really matter from a biological perspective.
But what you find then is that as you're going through life, as your cells carry on dividing, as your telomeres keep getting shorter, eventually we spot that people who have shorter telomeres are probably going to live less long than people of the same age with slightly longer telomeres.
And they're also more susceptible to certain diseases as well.
So this is a way that, you know, something fundamental and very molecular and, you know, sounds potentially quite complicated, but it has these sort of wide-ranging effects on our aging process globally.
So it's a little bit like, and I'm sorry to trivialize it.
I don't mean to, and I hope I'm not.
It's a little bit like those people who say, I've got a 720p TV for HD.
And my friend's got a 1080p one, full HD.
I can't tell the difference, but there is a difference.
Yeah, it's these things, you know, this isn't something that you can see with the naked eye, of course.
It's something that requires complex molecular biological techniques.
You can't feel your telomeres getting shorter, but this is happening all the time.
You know, as I'm speaking to you now, my cells are dividing, their telomeres are having little bits lopped off the end.
And ultimately, this almost invisible process is what caught, you know, one of the processes behind the aging process itself.
How do you stop that?
In the case of telomeres, the most promising thing is an enzyme called telomerase.
And this is actually an enzyme that we naturally have inside our bodies anyway, which is used for extending those telomeres.
And this was a really, really fascinating story.
In the late 90s, this was sort of hailed as the immortality enzyme because we thought, you know, this is the reason our cells age because their telomeres get shorter.
So if we can just extend those telomeres, you know, maybe we're all going to live forever.
Now, as you can tell, it's not all living forever.
So something must have thrown a spanner in the works.
And what happened was scientists tried adding an extra gene for telomerase into mice.
And what they found was those mice actually didn't live any longer at all.
They got a lot more cancer.
And the reason for that is that a cancer fundamentally is a cell that can just divide and divide and divide as many times as it likes.
And normally, this reducing length of the telomeres is a sort of safety mechanism.
So when the telomere gets too short, the cell will stop dividing for its own safety.
And so, you know, if a cancer cell needs to carry on dividing indefinitely, it's going to have to find some way to extend its telomeres to allow it to do so.
So by giving these mice an extra copy of telomerase, you're kind of pre-ticking a box on cancer's checklist in order to make sure it can get to the point where it can turn into a tumor.
So that, you know, took the wind out of the sails of that field for a while.
But luckily, a few scientists were, you know, doggedly persistent, even in the face of these seemingly adverse results.
And there's been some much more exciting work in the last five or ten years where the telomerase has been given not continuously, not by inserting a gene, but just transiently, temporarily to sort of top up the telomeres, but without giving cancer that helping hand.
And what they found is that they can make mice live longer and healthier, but they don't seem to increase the risk of cancer.
And one of the things also that research has shown that by changing the diet of mice, giving them a better diet, and maybe having them, I think, eat a little bit less than they might have done, that can also extend their lives, can't it?
This was one of the first results in aging biology.
And honestly, it shocks me that it happened so long ago and it took so long for us as a society and species to follow up on this incredible finding.
Back in the 1930s, experiments were being done in rats.
It has actually since been shown in mice and loads of other creatures as well.
But this first experiment was in rats and they cut back their rations by about 40%.
So this isn't just going on a diet.
This is like a continual, dramatic reduction in the amount of food they were taking in.
And what they found was that those rats could live about half as long again as compared to rats that were eating what they liked.
And most crucially, these rats weren't living longer in sort of geriatric ill health.
They were carrying on, you know, they were fitter, they were healthier.
Something that you always find reports in these papers about rats and mice by scientists is the rats had better fur, because I guess that's just a nice obvious thing that you can see as a research scientist playing around with these things in their cages.
But obviously, that's something that shows us it's really reversing the aging process globally.
It's not just that they're getting less cancer and deferring these diseases.
It's also improving the quality of their skin and their fur.
They're getting their plumper, fluffier little things.
So that showed us for the first time, having thought for the whole of human history that aging was some immutable fixed process, by an intervention as simple as dramatically reducing how much they eat, we can actually make animals live longer and healthier and basically slow down the whole aging process.
That's going to be a problem for us, though, isn't it?
Because we have, and especially now that the world is in lockdown, we have an absolute epidemic of obesity.
We all need to, I think, you know, as a society, be cutting back a little bit on what we eat.
And what I think actually this dietary restriction, you've got to remember, as I said, it's a long way beyond a diet.
There are people who practice this, but it's an incredibly niche activity because to literally, you know, cut back to say 2,000 calories a day if you're a man, so to lop 20 or 40% off the amount that you eat has huge effects.
They report that the hunger never goes away.
And no matter how long you do this, you never sort of settle into a new equilibrium.
You just carry on feeling hungry.
You can feel cold all the time.
There's some scientific evidence that shows it can give you thinner bones.
It can cause anemia.
So these are sort of slightly dangerous side effects that you could have.
It can reduce your immune system a bit.
It can even reduce your sex drive, which I guess for some people might be an advantage, but I think a lot of us would see that as a problematic side effect.
And so what this shows is that it's definitely worthwhile if you're a bit overweight, if you can try and cut back on some food and get your BMI, as we call it, in the sort of 18 to 25 Healthy range, but I think this dietary restriction is a much harder lifestyle intervention to recommend just because there are so many side effects and it's so tough to stick to.
I tried fasting once, this other idea of intermittent fasting, where you know you eat every other day, but I just find it so hard to go 24 hours without having any food.
So, you know, there's a joke in the aging biology world that dietary restriction that might not make you live longer, but it'll definitely feel like longer.
And so I feel like, for me, the trade-off just isn't worth it.
I know.
I've had more failed diets, God, than I think probably anybody on the planet.
That's a whole other issue.
Now, you talk a lot about senescent cells and how later in the book you say that killing those is a good thing.
So what are senescent cells and why do we need to kill them?
Senescent is just the scientific term for old.
And actually, these are cells that have divided too many times.
It's one of the ways they can become senescent.
And it's actually the responsibility of those telomeres that we were talking about just now.
If a cell's telomeres become critically short because it's divided too many times, the cell will just say, I'm not dividing.
And as we discussed, the reason for that, partly, is in order to try and be a cancer preventative mechanism.
So it stops these cells, you know, dividing indefinitely and turning into a tumor.
There are also, we now understand, a number of other ways that your cells can go senescent.
They can get damaged to their DNA.
They can just be stressed out.
And what they do when they become senescent, they don't just stop dividing, sitting there benign elders of the cellular community.
They actually emit a load of toxic molecules, which effectively accelerate the whole aging process.
And what's really exciting is that scientists haven't just observed these things accumulating.
We can go in and we can remove them.
And they've done this with mice.
They got some mice that were 24 months old, which is about 70 in human years, because obviously the mouse lifespan is quite a lot shorter than a human's.
And they gave them a couple of drugs, which removed these senescent cells while leaving the rest of the cells in their body, we think, largely unharmed.
What they found was the mice lived a little bit longer, maybe a few months, perhaps a few years, if we sort of translate that into human terms.
But again, like the mice on dietary restriction, they weren't living longer in ill health.
They get less cancer.
They get fewer cataracts.
They can run further and faster on a little mousy treadmill.
And again, that classic result, they've all got better fur.
So it really shows you that removing these senescent cells is a way to globally reverse the aging process and potentially treat many diseases and many other aspects of it all at the same time.
You say that we're full of rubbish, garbage.
Some people may be more than others, I think, in my experience.
But there's something called, is it lipofuskin?
It's full of, it's all the bits and pieces of detritus that we gather, misfolded proteins, fats, cross-linked together along with highly reactive metals like iron and copper to give us a problem.
So your body is in a constant process of recycling.
I think this is another thing that's just not apparent from looking at yourself in the mirror every day.
You don't realize that your skin cells are constantly turning over, your guts are constantly turning over.
And it's not just the cells themselves, it's actually the proteins inside the cells.
So protein, you know, I think when you say that word to most people, they probably think of the nutrition information on the side of a packet of food.
And so you sort of imagine it as some amorphous nutrient.
But actually proteins are the fundamental building blocks of life in many ways.
They're the little nanomolecular machines that go around like little nanobots, you know, doing all the stuff inside your cells.
They're also a lot of the structure of our body.
Proteins like collagen, you know, hold together huge, huge amounts of our tissues.
They hold our skin together, our blood vessels, and so on.
And so the way that our body has chosen to deal with a lot of these proteins, and particularly the ones that live inside cells, because they're so important, it actually can't afford to let them live for a long time because they can get damaged.
We spoke earlier about sugars and oxygen that they're just very reactive.
They can stick to the proteins and basically stop them working.
And so the way your body has chosen to deal with that isn't to sort of build proteins like tanks and make them invulnerable.
It's to constantly turn them over.
And a really important process in that involves this lipofusin.
So it involves being gobbled up by a little thing inside your cell called a lysosome.
And when the lysosome consumes those proteins, it'll try and break them down.
But unfortunately, there are some types of damage it just can't break down.
And that means that there are some parts of the body where it accumulates this waste.
It just sort of gets engorged.
It gets fuller and fuller and fuller.
And a really classic place where this happens is heart disease.
So we imagine in cardiovascular disease that our arteries are lined with sort of globs of fat and lard, because that's what we're always told about, you know, avoid fat, avoid cholesterol.
But actually, what it's really full of are immune cells that have gone up to clear up a sort of slick of fat and lard.
And their lysosomes get engorged by various products that various sort of oxygen, oxidized, sorry, their lysosomes get engorged by various products that have been oxidized or have been reacted with sugars.
And it's that form of cholesterol.
And because these immune cells all sort of clumped together in these huge globs, that is what is lining our immune cells.
So it's actually not, you know, just basically slicks of lard that are lining our arteries.
It's actually these immune cells that have come to clear up those slicks of lard.
And so these lysosomes and this lipofusin is a fundamental driver behind everything from heart disease to strokes.
And you say that what we need to do to make this more efficient and better for us is to keep our protein pristine.
Yes, so we need to find various ways to hopefully clear out some of that lipofusin.
And there's another example of there's a disease called age-related macular degeneration, which is the single biggest cause of blindness in older people.
And that's caused by accumulation of a different form of lipofusin in the cells in the back of our eyes.
And there are various treatments that are being devised to either break down that lipofusin by providing our body with the tools to do that, which it doesn't have naturally, or alternatively using drugs to encourage our cells to clear out that lipofusin to inject it into the bloodstream and hopefully have it cleared up and then excreted.
So yeah, by getting rid of this sort of toxic agglomeration of molecules, we can hopefully reverse that terrible disease.
Any of this going to happen in our lifetimes?
Absolutely.
I think that the senescent cells work is the thing that most excites me and might be available in the nearest term.
So these senolytic drugs that have been trialed, some of them are pre-existing human drugs.
What that means is it's very easy to repurpose them.
But also it's the case that there are about 20 or 30 companies working on a variety of different approaches to remove these senescent cells.
The first human trial of senolytics starts in 2018.
So I think it might just be a few years before these kinds of treatments are available in the clinic.
And obviously there are more advanced things.
I talk in the book about gene therapy and stem cell therapy, you know, which might be 20 years away rather than two or three years.
But still, a lot of this stuff is going to happen in time for people alive today.
Before we leave the science of it all, Andrew, I've got this long list of points here.
You talk about running repairs.
In other words, not doing great fundamental changes to us, but the possibility that we Might be able to do little tweaks along the way.
When I talk about the different ways that you can treat aging in the book, I break it down into these four different sort of concepts.
One of them is to remove, one of them is to replace things, one of them is to repair, and then the final one is to reprogram our biology and try and stop us aging in the first place.
And I think that there's just going to be a huge diversity of treatments.
So we talked already about removing senescent cells.
That's a very easy concept to get your head around here.
It's a bad thing.
We want to get rid of it.
And it's actually the same with the lipofusin that accumulates inside our cells.
That's a problematic material.
We want to get rid of it.
We want to give our body the tools to do that.
But there are some situations where you don't want to remove things.
And I think a really good example of that is DNA damage.
So the damage that happens to the instruction manuals inside our cells.
So it wouldn't even make sense to talk about removing our damaged DNA because every cell needs that DNA.
It's a crucial instruction manual.
And so there are going to be places where we're going to have to put in various mechanisms.
We might use drugs.
We might use other treatments to try and repair these things in situ because it just doesn't make sense to get rid of them.
Right.
And there are also little bits of routine regular maintenance.
Now, I have to tell you that one of the consequences of being in lockdown is that maybe certain aspects of my health are not quite what they might be.
And today I'd forgotten about doing this.
And today I've gone and done it.
I haven't done this for about two years or so, but I went out and I bought probiotic yogurt because, you know, for me, not to be indelicate about it, but the health of the gut for all of us is terribly important.
And that is something that you actually talk about in the book, that it's very important to keep tabs on the bugs that we've got in the gut, the good bugs.
So you talk about how, I'm trying to pronounce this word here, bifidobacteria and lactobacillus are both a good thing.
There you go.
I'm only going to do that once.
Yeah, what we found, and this is actually a hallmark of aging that has been really, really developing rapidly in the last few years.
We've noticed that as people get older, you can actually create something called a biomarker.
So you can effectively work out their biological age by monitoring the rates of different bacteria in their guts.
Now, we're not currently at a stage, unfortunately, where we can prescribe particular treatments, but we can, we've got some examples in the lab of where this works.
So there's some interesting experiments that were done in a species called the killifish, which is this bizarre little fish that lives basically in ponds.
They're almost puddles, frankly, in Africa.
And so they suddenly, when the rainy season starts, these little pools, these little puddles fill up with water.
And so their eggs hatch, basically.
They grow up into adults and they have to very, very rapidly go through their life cycle.
So they only live a very short, matter of weeks or months compared to obviously humans that live such a long time.
And they did an experiment where they basically got some older fish and some younger fish and swapped their microbiome.
So swapped the bacteria and other organisms they have in their guts around.
What they found is that if you give a young microbiome to an older fish, then again, like all of these interventions, the fish effectively gets biologically younger.
They lived a bit longer and it's hard to do like detailed autopsies on fish because they've got quite a different physiology to us.
But they noticed that they darted around the tank a bit more, which sort of fishy proxy for delayed frailty.
So that really shows us that maybe, you know, changing the guts that we have, changing the bugs that we have in our guts can have a huge influence on how we age and our health.
What about these people?
And it's not in the book, and I'm trying to find a delicate way of putting this, but I've heard of some people who've had, what do they call them, fecal transplants, poo transplants, in other words, which sounds horrendous, but there are people who say that that benefits them.
Yes, and this is a treatment that's used for a disease called C. diff, which is a bacterial infection that you can get in your intestines.
And actually they found one of the most effective ways to get rid of C. diff is to give you the good bacteria of somebody who hasn't got the infection.
And those good bacteria will then, you know, fight on your behalf effectively to clear out these problematic bacteria from your guts.
And there are a few different ways you can do this.
You can pop a little freeze-dried pellet of bacterial material, or you can have it inserted at the other end, shall we say, which sounds a lot more exciting.
And I think this is one of these things where perhaps we are going to have to swallow our pride and our sort of disgust, perhaps even literally, because, you know, obviously if you had such a serious bacterial infection, I would definitely take the treatment.
And if it's something that's going to potentially slow down our aging, hopefully we can find the least invasive and unpleasant way to deliver those bacteria.
But I think I'd probably go for it.
Okay.
Well, I'll probably go for the sanitized pellet myself, if that's all right with you, Andrew.
I don't know that that just came into my mind there because I'd read a few news stories about it this year.
Now, look, the scientific aspects of this are all very well, but there are philosophical aspects.
And of course, the one question that everybody who interviews you will probably put to you is, it's all very nice talking about making people live longer and making some people perhaps live indefinitely.
But if you do that, you have more people on the planet.
Where are we going to put them?
That is definitely the question I get asked most often.
And I don't know if you remember going to dinner parties and weddings, but whenever I told people at such an event, I was working on a book on aging, invariably, even though this biology is so fascinating, the first thing they'd ask me is, where are we going to put all the people?
And I have a couple of different ways of looking at this.
The first is to address these various philosophical, ethical quandaries head-on individually.
And in the case of overpopulation, I just think we're thinking about it all wrong.
Because we think about the number of people on the earth as the problem, but what's really the problem is the amount of resources that we use.
And if we were to take carbon dioxide as an example, so use the problem of climate change as a sort of exemplar, the top billion people, the richest billion in the world, emit something like half of the CO2.
And that means that there's six or seven billion people that are emitting the other half.
And so that means that if we want to bring those six or seven billion people up to a sort of quote unquote Western standard of living, we are already, regardless of what we do about aging, regardless of what we do about birth control or any other methods of trying to improve, reduce birth rates or change population that way, we're going to end up in a situation where we need to find a much lower intensity way of maintaining our quality of life.
And that happens irrespective of what we do about aging.
As it happens, I think then even if we were to completely cure aging, it would have a surprisingly small effect on population.
So if you, I did some calculations where I imagined that we literally cured death, which obviously isn't something that we can, you know, we can talk about because even if we were to cure aging, you could still get hit by a bus, you could still get an infectious disease that kills you and so on and so forth.
But even if we literally cured death, global population would only go up by about 0.75% a year, which isn't nothing.
But equally, I'd happily work 0.75% a year harder to deal with problems like climate change if it meant that we could eradicate this largest single cause of human suffering.
And that sort of brings me onto the second way that I think about all these problems, and that's to switch the question around.
You know, we've got a huge bias toward the status quo as humans, I think.
And, you know, we live in the society we've accepted aging, as we talked about, you know, back in the first part of our discussion.
Imagine that we lived in a society where there was no aging, where people live much, much longer lives and they were healthier right until the very end until they basically just got killed by something.
And we were staring down the barrel of a hugely overpopulated planet.
We had 20 billion people on planet Earth.
There are loads of different things we could do.
We could try and reduce our carbon footprints.
We could try and reduce the amount of land we use.
We could do something about birth rates.
I think the absolute last thing you would do is invent aging to try and solve this problem.
Because even if you decided that you needed to kill people, there was simply no other way to try and get the population to get the environment back into our control.
Would you really do it by a 20 or 30 year drawn out process of degeneration where slowly they got more frail and lost their faculties and lost their continents and watched their friends disappearing around them and eventually got a disease that was sufficiently severe to gradually kill them?
That just isn't the way that I'd choose to solve that kind of problem.
And I think that applies to a lot of these ethical questions.
You reverse it and you say, you know, if this was a problem and I had to invent aging to solve it, would I do that?
And the answer is almost always no.
And you talk in the book very early about the costs of aging.
And you point out that there are both direct and indirect costs of aging, which is what you've just discussed.
You know, the fact of the matter is that the way of things now, people get older, they get sick, and then ultimately they die.
You know, it's not the way that it has to be.
And economically, if you made it another way, it doesn't have to bankrupt nations.
Quite the opposite.
And I think this is one of the things that's often overlooked.
You know, we say it would get harder to solve climate change if we had more people because they were living longer.
But actually, if you think about, you know, what does the health service pay for?
A huge amount of our healthcare spending is spent on the chronic diseases of old age.
And that's because, you know, things like cancer, things like dementia, things like heart disease, you suffer from these things for years and years before they kill you.
So that means, you know, in terms of the healthcare, in terms of the medication, that all adds up.
Then there are these indirect costs, you know, where people give up work, perhaps because they're too ill to work anymore, or perhaps because they want to look after one of their relatives who's too ill and, you know, requires more full-time care.
And so by the time you add up all of these different costs, you can turn that around and say, if we could do something about aging, these would all be savings.
And then we could put some of that huge amount of saved money toward solving other problems in the world, like climate change.
So often, actually, curing aging could significantly ameliorate a lot of these things that we think it would aggravate.
But before we get to the point where we've evolved to people who live longer, by changing ourselves and what's inside us, there are going to have to be treatments administered and various other things to get us to that position.
And all of that is going to cost money and resources.
So part of that is going to be making decisions, don't you think, about who lives longer.
And that's a qualitative decision, isn't it?
Maybe we'd farm it out to algorithms.
Maybe there'd be a panel of experts who say, well, there's Einstein over there.
He's 85, but look at the contribution that he's made.
He's got, you know, at least another 50, 60, 70 years in him.
We need him.
We'll keep him.
We'll give him the treatments.
There's Howard Hughes over there.
He does radio shows and podcasts.
Well, to tell you the truth, he's had a good innings.
Time for him to go.
We'll get involved, won't we, in the intermediate stage in some difficult decisions?
I really hope that these treatments are going to be rolled out universally because it doesn't matter who you are.
Aging is phenomenally expensive.
And there are these huge knock-on costs to society.
Maybe Einstein would be tremendously sad if we decided not to keep his wife alive or his kids or his family or his friends.
So I think the idea that we pick and choose, no person is an island.
And so when you make these ethical decisions, I think the only sensible way is to do it universally.
And to go back to the economic argument, I think the economics is going to be such that it only makes sense to roll these out as widely as possible.
Because the fact is that aging is so expensive.
If we can reduce that across society, we're going to make bigger savings.
But how would you stop people getting bored?
That's the one thing that you can't fix.
If you make somebody live to 150, every time they do something, it'll be something they've done before.
It's like seeing the scenery come round again in an old movie.
They're in the back of a stagecoach.
You see the same scenery go round and round and round.
That would be a psychological problem we'd have to deal with.
I just don't believe that.
And the reason for that is I can't imagine why I would want to die in the next year or why I'd want to get dementia next week.
And I can't see why that would change when I'm 80.
The number of experiences that I've got to have, there are so many thousands of wonderful films to watch.
There's music being written.
There's, you know, there are countries to visit.
If you just think about this in quite a sort of glib mathematical way, there are, you know, if I were to visit a country a year, it would take me almost two centuries to visit every country in the world.
And obviously there's more than one interesting thing in each country.
So I just think there's an absolute vastness of human experience.
And, you know, beyond that, as people are living longer, they're getting more experienced.
We talked about getting better at your job.
We're going to have people composing music that we just perhaps couldn't even imagine in our current lifetimes.
We're going to have great artists, great poets, great songwriters, all these different people producing all this new stuff for us to absorb as well.
I think there's going to be more stimulation than we've got time to do, time to absorb, even if we have vastly extended lifespans.
And that's before you go into the huge technological change that's going to occur.
In the year 2080, imagine what virtual reality is going to have in store.
Maybe we'll be able to do a bit of space tourism.
I've got no idea what the future holds, and I'm really excited to find out.
I'm with you on all of that.
And sadly, I'm a little bit older than you, but keep working on it, Andrew, because that's the world that I want to go into.
Andrew, thank you very much indeed.
Tell me what the book's called and who publishes it, will you?
It's called Ageless, The New Science of Getting Older Without Getting Old.
In the UK, it's published by Bloomsbury and it's out now.
And in the US, it's published by Doubleday and it's going to be out on the 23rd of March.
So get that date in your diary or pre-order wherever you can buy your books.
And you, Andrew Steele, are a fantastic ambassador for all of this.
Thank you for opening my mind on it.
Andrew Steele, your thoughts about him and his contribution to this show?
Gratefully received.
I thought he was an amazing guest.
What do you think?
Anyway, more great guests in the pipeline here at the Home of the Unexplained.
So until next we meet, my name is Howard Hughes.
This has been The Unexplained Online.
And please, whatever you do, stay safe, stay calm, and above all, please stay in touch.
All of those things, in any order you like.
Thank you very much.
Take care.
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