Horizon (1964) s00e73 Episode Script
Immortal - A Horizon Guide to Ageing
There is one inevitability in life - as time passes, we age.
It might creep up on you, but you only have to look back to spot the changes.
'Do you know that song? We've sung it before.
'Sing it with us this time 'and do the actions as though you were swimming, like Humpty.
' You know, I'd like to think that I've aged or grown old gracefully, but there's no question about it - I have grown old, I've got the evidence to prove it.
It's hard to believe, but it's 45 years since I first started presenting on television.
Since then, my hair's gone grey, and my forehead's so wrinkled, I can screw my hat on.
What I want to know is, does it have to happen or could I stop, or even slow down, the ravages of time? It's a question that has long fascinated amateurs and alchemists alike and, for the last 45 years, Horizon and the BBC have followed as ageing has become the increasing focus of serious scientific studies.
From the earliest days of grappling for answers I think we are miles and miles away from solving the problem of ageing.
We're just right at the very beginning.
.
.
To extravagant promises of longer life.
I would think, by the end of the century, that we will be living to 150 to 200 years.
We've witnessed macabre treatments.
What in fact you are doing is injecting a beef broth.
We have met those who have claimed to have found the ultimate solution.
This was the first discovery that we could actually find a way to slow down the ageing process with a single pill.
And glimpsed a brave new future.
Does it spontaneously start to beat in the end? Yes.
Yes, absolutely.
Wow, that is marvellous.
While some scientists have been driven by the desire to alleviate suffering Having lost my dad to disease, I just want to change the world.
.
.
Others have been spurred on by an all-too-human desire.
Sandy and I have been working on life extension to make the world safe for Durk and Sandy, a couple of gourmets who want to live a long time and stay young.
This is a story we all have a vested interest in, but, after 45 years, how much has science discovered about why we age? And are we any closer to achieving the dream of immortality? We all like to remain young at heart, but wouldn't it be better to just stay young? Perhaps that's why we are all drawn to people who claim they've discovered the elixir of youth, irrespective of how colourful those claims might be.
'Durk Pearson and Sandy Shaw 'have written a bulky manual 'of their life extension techniques 'which has swiftly sold 'more than a million copies in the United States.
' Thank you.
Thank you! I read it every day and use it as, like you would The Bible.
And I'm young and I just want to stay that way so that when I get older, I won't have the problems that people have now.
'Both are in their early forties 'and every day, they consume over 35 different chemical substances 'which they believe are helping to maintain their youth 'and prevent the ravages of age.
'Although neither is a doctor, they did qualify as research scientists, 'and they regularly scan the medical literature 'for news of drugs which might stop them growing old.
This is ornithine.
It's an amino-acid.
It causes the release of a growth hormone by a gland in your brain.
Growth hormone causes you to burn off fat and put on muscle like a teenager with very little exercise.
It also has a very powerful immune stimulant and makes your body better able to fight off infectious diseases and even cancer.
This is vitamin C.
It's an extremely important nutrient to help avert a major form of ageing damage.
In fact, it's so important that the brain and spinal cord have special pumps that bring the concentration of vitamin C up to 100 times that of the general circulation.
This is vitamin B3, niacin.
This is able to reduce the cholesterol in your bloodstream by about 25% within two weeks of when you start taking it.
A lot easier than going on a diet.
We want to live a lot longer.
We'd like to remain young and healthy as long as possible, perhaps even indefinitely.
We and many other people now alive have a very good chance of having an indefinite lifespan, one limited not by ageing or cancer or cardiovascular disease, but rather one limited by accidents, murder and suicide.
Fanciful, maybe, but such claims reflected a real shift in modern attitudes to ageing.
Thank you.
In the post-war era, increasing prosperity and improved healthcare meant many were living longer.
By the 1960s, average life expectancy had increased by nearly ten years in the space of one generation.
The downside was that with longer life came the problems of old age.
Now, just a second, stop.
I think you could walk without it.
No, I can't.
- Why don't you let me take it away for a minute? - Why not? And not just physical disability, but the increased likelihood of a deteriorating mind.
This is essentially an organic deterioration of the brain in which the tissues are breaking down and it's shown clinically as loss of mental powers initially.
The memory goes, this is particularly striking, they can't concentrate.
One doesn't know whether senile dementia is a disease which has, in fact, superimposed on ageing or whether one can look on it simply as the extreme of old age.
And this is what one is trying to find out before one joins the ranks oneself.
The early pioneers in age research were driven by a sense of this pressing social need.
Professor Alex Comfort, who would later become famous for his work on The Joy Of Sex, was one of those determined to find a way of combating the effects of ageing.
One of the first things that every human being learns in childhood is that old people die.
Of course, we can die before we're old, but if we escape all the other hazards and bad luck, we know old age gets us in the end.
In other words, we've got a fixed lifespan and, as more and more of us are surviving to that lifespan, old age accounts for more and more of the work of our medical and social services.
Research money needs now to be spent on alleviating all these special disabilities which go with age.
And I would like to see British biology well in on this attempt to understand ageing and to do something socially and practically useful about it.
And if you wonder whether it's worth it, whether it's worth trying to do something about old age, just you look at the old people around you, the old people you know.
People say old age has its compensations.
Well, maybe it has.
That's very nice, yes.
But you don't ask for compensation unless you've been run over.
Old age is a pretty miserable business.
For Professor Comfort, the first practical step was for scientists to try to get to grips with what controlled this miserable business.
What they are trying to find out is whether there is a single major clock mechanism which determines the progress of age changes and whether it can be slowed.
To find out, in other words, which components in the developmental programme of living are the timekeepers.
The hope was that there was one single dominant factor that acted as a timekeeper.
If scientists could discover that, then maybe they could alter it and enable people to live more healthily for longer.
At the time, there was a broad theory of why we grow old, that ageing was part of a programme in a way in-built in all living things.
'Our voyage through life is programmed, 'just as the holes in the Pianola roll 'dictate the notes to be played and the length of the tune.
'In the same way, the DNA in our cells 'dictates the growth and death both of our organs and of our whole body.
'But, sooner or later, the holes dictate the final chords 'and the roll must run out.
'Professor Bellamy of Cardiff University.
' Many organisms are programmed to live for a set time to reproduce and then immediately die.
The migrating salmon is a good example of this.
It spends most of its life in the sea.
It grows, matures there, it migrates up the river to spawn and then immediately afterwards dies.
So that is the total programme of its life, and natural selection in fact has produced this.
To try and pinpoint a more precise mechanism for ageing, scientists needed to discover more about how the body aged.
The American Institute for Ageing embarked upon an ambitious study, subjecting dedicated volunteers to a battery of tests for over two decades to see what happened to their bodies over time.
'One person who has been coming every year since 1959 'is Mr Young.
'On average, the capacity of the heart to pump 'declines by 33% from age 30 to age 75.
' 174 over 80.
'The lungs do worse than the heart, 'their capacity is down 40%.
'The liver lasts better, 'it loses only 10% of its capacity, 'compensating for the fact that blood flows through it 'much less efficiently.
Put your arms to your side.
'The kidney suffers especially, 'its capacity to filter is down by 44%.
' The results revealed just how complex a process ageing was.
All the organs seem to deteriorate at different rates, making it unlikely that there could be one single mechanism at work.
But what was indisputable was that the body went downhill.
The study suggested that ageing might be caused by the battering our system takes simply in the business of everyday living.
Damage slowly builds up over time.
Service! And we begin to break down.
Professor Comfort likened this to a film running through a projector too many times.
This old film, The Wonderful Hair Restorer, has been shown hundreds of times.
In use, it's accumulated random wear, scratches, breaks, loss of frames where it's been mended.
It's now quite unclear, and prints taken from it will be worse still.
Now, this random damage is what we engineers call noise, it's interference which makes the original information contained in the film harder and harder to read until, really, there is very little left of the film as it was originally made.
Another early expert on ageing, Denham Harman, thought he knew what might be causing the damage and the answer lay not in humans, but in mice.
He reasoned that mice are so short-lived because of what became as the Oxidative Stress Theory of Ageing.
Their high metabolism means mice use lots of oxygen.
The more they breathe, the more it creates dangerous reactive substances called free radicals that damage cells and organs, causing the mice to rapidly age and die.
Denham thought the same principle could be applied to humans and he also suggested a solution, substances that could prevent the damage happening.
We know them today as anti-oxidants.
People began to apply some pretty basic logic to this discovery - if you can increase the anti-oxidants in the body, perhaps through what you ate, then you could stop the free radicals causing damage and thus, slow ageing.
However, where was the proof that this would work? Two brothers thought they had it.
They spent 20 years studying the population of Okinawa, trying to work out why so many people there lived such long and healthy lives.
You walk down the street and there's an elderly lady sweeping outside of her little restaurant, you look at her and you think, "There's a nice 65-year-old lady, "she's probably retired, a part-time job, keeping busy," and then you find out, you know, she's 101.
'The explanation for this extraordinary phenomenon 'begins in the most ordinary of places.
'Like every town in Okinawa, 'the fruit and vegetable shop in Egimi 'lies at the heart of village life.
' 'It's here that Bradley and Craig 'believe the source of the Okinawan miracle can be traced.
' These veggies are a type of a sweet potato.
It's called, in the local dialect it's called "beni-imo.
" And beni-imo, it's a purple sweet potato, isn't it? Oh, look at that purple colour! You can see that purple, the purple really comes out more when you cook it.
The key is to get a lot of vegetables that are, with the very colourful, oranges, like these carrots here, dark greens and yellow vegetables, eryou might think of it as a rainbow diet.
'For the past 20 years, Bradley and Craig have been analysing 'the life-enhancing Okinawan ingredients.
' We got reds here and the tomatoes, the peppers.
You've got green peppers here.
'They've identified a number of crucial properties 'that guard the Okinawans from disease, from the anti-oxidant rich vegetables that protect against cell damage 'to the high quantities of soya proteins.
' We believe that this is playing a part in, in their low rates of hormone-dependent cancers.
'Okinawans have amongst the lowest rates 'of breast and prostate cancer in the world.
If we lived in the West more like the Okinawans, you could probably close down 80% of the coronary care units, one third of the cancer wards and a lot of nursing homes would be out of business, simply because these people are so healthy.
Hmm, he passes the test, this is really good.
Goya chempu! Thank you.
The Okinawan soy and rainbow diet is stuffed full of anti-oxidants.
Its apparent effect in this says, "Yes, the oxidative stress theory of ageing must be correct.
" But, while anti-oxidants have become big business, other studies have found the theory less convincing.
Scientists at the University of Texas investigated oxidative damage in a different rodent - the naked mole-rat, an exceptionally weird-looking creature that seems to have traded beauty for longer life.
If you look at a naked mole-rat, it's a 30-gram animal, the same size as a mouse.
Yet it lives ten times longer than a mouse and it clearly is beating the odds, so we predicted that, given the fact that they live so long, that they would have very low levels of oxidative damage.
So Professor Shelly Buffenstein set out to test the theory, but things didn't pan out as expected.
We found that, even our youngest animals had three to ten times more oxidative damage than a similar physiologically age-matched mouse.
Clearly, it was possible to have high levels of oxidative damage and live a long, healthy life.
But this was not going to go down well.
What Shelly had found would shock colleagues who'd worked in the field for years and threaten the entire anti-oxidant business.
People didn't want to accept what we found because there's too much investment in this area of research, anti-oxidants are a multi-million dollar industry, as you know.
When we tried to publish it in Science, the first review came back, "Well, you guys don't know how to measure this technique, "so that's why you're getting these crazy measurements.
"Send it to a real lab that knows this kind of thing.
" So Shelly repeated the experiment and found that oxidative stress didn't make a difference.
What to me seemed so fascinating is, they've put their little finger up at ageing.
Many people still swear by a diet rich in anti-oxidants, but oxidative stress is really too simple an explanation as to why we age.
But scientists did have evidence that you could slow ageing and it did involve food, but not what you ate, how much you ate.
And once again, mice take centre stage, this time mice on a diet.
This particular mouse is .
.
48 months old.
That's longer than any mouse ever lives who is not on a restrictive diet.
This one has been restricted since about 12 months of age.
Normally, mice never live longer than 36 months.
This means that the ageing process has indeed been retarded by this kind of procedure.
One can slow down ageing.
This is the equivalent in human terms to increasing maximum lifespan from the present level of about 110 years, the longest anybody ever lives, to 150 to 180 years.
This kind of study is, with a high order of probability, directly translatable to human use.
Researchers were uncertain why calorie restriction might work.
Their best guess was that it made the in-built ageing programme run slower.
For some, the evidence proved too tempting a prospect to pass up, including Dr Walford.
'For a man in his sixties who fasts three days a week, 'Roy Walford seems to be living proof 'that eating less but eating well keeps you fit and young.
' My own technique for extending maximum lifespan includes a programme that I call "under-nutrition without malnutrition.
" That means lowering the caloric intake but keeping the nutritive value of your food very high and this, if one translates the animal data into human use, should extend lifespan by a very substantial amount, depending on what age you are when you begin that kind of a programme.
Despite his certainty, Walford was taking a leap of faith and it would take a very hungry lifetime to see if the bet paid off.
But that hasn't stopped a host of others giving it a go.
In 2009, Michael Moseley went to meet one of them to see what effect 16 years of living on just 1,600 calories a day might have had.
- Hello.
- Welcome, hi! - Hello, very nice to see you.
- First impressions - very youthful, I have to say.
- Oh, thank you.
Very youthful.
Can I just look at your face? Me? I thought you meant the house.
No, I think you, good, very good.
'Calorie restriction isn't simply about eating less.
'Dave eats salad on an industrial scale 'to get all the vitamins and minerals he needs.
'At 51, he certainly looks good on the outside.
'But I wanted to know what was going on inside.
'A series of tests would compare our bodies 'and determine who was biologically younger.
' Could you sit down and sit back? HE LAUGHS 'How embarrassing, I hadn't realised how competitive I am.
' HE COUGHS - Are you going to pass out there, mate? - I was going to pass out, let me tell you.
'Finally, our skin was analysed 'by cosmetic surgeon Mr Jaya Prakash.
' Right, that's better.
Oh, what a big funny nose I have.
His skin is better than mine.
According to these graphs, his skin is marginally better.
- Yeah, yeah, yeah.
- Marginally.
- Marginally.
Yes, how old do you think we are? - If you want me to guess - Yes.
Dave would be 35.
Mmm-hmm, and how old do you think I am? HE LAUGHS You reckon I'm 50 and he's 35? - Yeah.
- OK.
Yeah, that's right, that suits me.
OK.
I am 51, and he is 51.
- We're actually the same age within a month.
- Really? Well, he may look great but most of us, and me for one, would really baulk at the idea of a lifetime of salad.
But one scientist discovered how calorie restriction worked and that it could work irrespective of what you eat, and then everyone sat up to take notice.
The secret is in our genes, in the genetic makeup within our DNA.
I know about a dozen people voluntarily restricting their food so that they're for the most part hungry during the day, in the hopes that that will extend their lifespan, but you have to be hungry for this to work.
And I tried it for about a week and it meant eating baby food and just a few vegetables, and I felt hungry all the time and I thought, "If this is going to be my life for the next hundred years, I don't want it.
" David Sinclair wanted to find out how calorie restriction worked to see if he could create its effects without starving himself.
He began by studying yeast, but it wasn't what the yeast ate that concerned him.
Rather, it was their genes.
The organisms that I'm particularly excited about are yeast cells.
These are yeasts that you put in your bread and your beer, but actually, they have a lifespan of about a week and the goal, about 15 years ago, was to find out why do they age and what can we do about it? And what we were looking for were genes that, if you delete them or you add an extra copy of them, that they live longer.
We found a set of genes that do that.
They're called the sirtuin genes, and really what was very exciting was that just adding one extra copy of a gene called Sir2 could greatly extend the lifespan of those yeast about 30%.
David had found a gene in the yeast that seemed to directly influence ageing, an astonishing discovery.
So he removed the gene to see what happened when he then restricted what the yeast fed on.
What the team discovered was that, when this gene wasn't there any more in the yeast cells, they didn't respond to the diet calorie restriction, they didn't live longer, so we knew immediately that this gene, maybe others, were really important for this diet to work.
What was a really amazing discovery was to realise that this diet and these genes were part of the same system and that was a real breakthrough.
David had discovered why calorie restriction worked.
He now wanted to see if he could get the benefit without going hungry.
After ten years, he found a molecule called resveratrol that seemed to mimic the effect of the diet.
The amazing thing about this molecule is, when you feed it to life forms, so a yeast cell or a worm or a fly, even a mouse that's obese, they live longer and they're much healthier.
And this was the first discovery that we could actually find a way to slow down the ageing process with a single pill.
This could be the ultimate dream - an anti-ageing pill.
Glaxo-Smith-Klein paid 720 million for David's company and, while it's too early to know if resveratrol works in humans, David isn't waiting to find out.
I'm a scientist.
Occasionally, I experiment on myself as well and so I started taking resveratrol as soon as we had tested it on yeast cells.
Now, looking back, that was a little mad.
We didn't know if it was toxic, might have even caused cancer.
Fortunately, we now know that resveratrol is, as far as we can tell, relatively safe.
My wife started taking resveratrol, my family does.
Now, I don't endorse it, it's still an investigational molecule, but I felt that the signs were strong enough for me to take that risk and I know what's going to happen if I don't take it.
The ability to just pop a pill to stop the ageing process sounds too good to be true, and at the moment it still is, but what the work did show was how important our genes are in the ageing process, and our increased ability to understand our genetic makeup has revolutionised our understanding of how we grow old.
This expanding knowledge of genetics has turned communities where people make a habit of living long lives into superb laboratories for ageing research.
In New York, Professor Nir Barzilai studied a Jewish community full of centenarians to work out what role their genes played in helping so many of them reach a hundred.
I think the ageing can be redefined after you see so many centenarians like I do, and I'm really jealous of them.
They might look old to you, but you see that their life is so meaningful.
- Hi, Grandma, it's good to see you again.
- My darling, I'm so glad you came.
The old man with the beard is my baby grandson.
Ria Tauba is 102 and part of Nir's study.
The chances of living to a hundred are only one in 10,000.
Cheers, that's great.
The question for Nir was how much of their longevity was down to genes and how much could be about lifestyle.
- Are you going to have some lox, Grandma? - What could be bad? What could be bad? There you go.
Eat like this, and you live to 102.
So his team conducted physical and cognitive assessments and asked the 500 centenarians a range of lifestyle questions.
Did you eat yoghurt all your life? You know, were you a vegetarian? What was your interaction with the environment? And I think the surprising thing for us is that we don't have yoghurt eating, we don't have a single vegetarian.
We have just one person who was an athlete.
Nir gathered their blood samples and prepared to map their genes.
After five years, Nir finally had some results.
He found a gene key to longevity and has since found two more.
Two of those genes seem to be relevant to cholesterol.
Basically, they increase the good cholesterol in a significant way.
There is no drug currently that does it so effectively.
And another gene seemed to be very important as preventing diabetes.
For most of us, how much we eat and exercise is key to how healthy we are and to how long we live, but there was something rather shocking about these centenarians.
30% smoked two packs of cigarettes for more than 40 years.
Because our centenarians have longevity genes, they are protected against many of the effects of the environment, that's why they do whatever they want to do and they get there anyhow.
Those key genes apparently overpower the effects of diet and lifestyle and leave a wonderful legacy for the next generation.
So, Grandma, what are your plans for your next birthday? The children of these Jewish centenarians are 20 times more likely than the general population to live to be a hundred.
- If you have a nice guy for me, I'll go on a date.
- OK.
THEY CHUCKLE For the rest of us, what our genes might have in store is a lottery.
There's no way of knowing whether we have long life in our DNA.
But is there anything we can do to change the odds in our favour? Ageing and death are both programmed into our genes.
It doesn't mean it always has to be that way.
If we can figure out what the programme is, then we can try to fix the programme and to stop ageing from taking place.
Scientists searched for ways of fixing the programme by experimenting with selective breeding.
Not on humans! Instead, they chose something much shorter lived - they chose the common fruit fly.
A team at the university of California devised a simple breeding programme in which only eggs from older flies were allowed to survive while those from younger flies were destroyed.
The essence of the experiment is to say to the fruit flies, "OK, you don't get to reproduce until you're older.
" And that means you have to survive until you're older, and it means also when you're older, you have to have the physiological ability to reproduce when you're older.
And natural selection screens the flies under those conditions for postponed ageing automatically.
'The only eggs allowed to hatch are those with the genes for long life.
'This single experiment has been going on for over two decades.
'Over hundreds of generations of selective breeding, 'the fruit flies have slowly doubled their lifespan.
'But the most remarkable thing about this experiment 'is what extreme old age does to these flies.
' The much longer-lived fruit fly turns out to be very different from what you might imagine.
These fruit flies that have increased lifespan are far more athletic than normal fruit flies, they fly for much longer, walk for much longer.
They are vastly more resistant to a variety of stresses, they are very robust in that sense and they certainly set to enjoying life, at least from a sexual standpoint.
A longer life and more sex, sounds like a win/win situation for fruit flies.
But, really, could we do that with humans? Use selective breeding to lengthen our lives? Think of the ethical nightmare of that.
So if we couldn't breed for immortality, could we still find the answer somewhere else, deep within ourselves? Scientists working in another area of ageing research thought they had it.
Only this time, the insight came from not studying the very old, but the tragic cause of ageing in the very young.
In 2000, Horizon met Ory Barnett, a young boy suffering from the rare disease Progeria, which causes early ageing.
Although only three, Aury already had wrinkles, stiff joints and thinning hair.
Sufferers often go onto develop arthritis and heart disease and most will die of old age whilst still in their teens.
I thought that he was just a perfect little boy and to find out that he had, you know, things wrong with him, it was just, it was very upsetting.
'Scientists now believe they can explain 'why these children age so suddenly 'and this is offering clues to how we all age.
'They have discovered that there is a time bomb inside our cells 'that causes them to stop dividing 'and, for Progeric children, 'the fuse on this timebomb is the wrong length.
'Inside every cell in our body, 'at the end of our chromosomes, 'is a piece of DNA called a telomere.
'It stops the DNA from fraying as it divides.
'But, every time a cell divides, the telomere gets shorter.
'Eventually, the telomere shortens to a critical length 'and the next time the cell divides, 'the telomere can no longer protect the fraying DNA and the cell dies.
'What scientists now know is that Progeric children 'begin their lives with unnaturally short telomeres 'and that is why they age so quickly.
' If the shortening of the telomeres could be slowed or reversed then, perhaps, there was a hope of a cure for Progeria and a chance of influencing the way we age.
Scientists knew that an enzyme called telomerase could repair telomeres.
Researchers at the university of Texas inserted the gene for telomerase into skin cells taken from an old man and waited to see if they started producing the enzyme.
And I can remember the postbox bringing me the gel, this is a piece of film showing that these cells had telomeres.
And I told the postbox, "Remember this moment," because it was one of those, it wasn't one of these eureka sort of things but it was almost like that, because we were sitting there and I realised, for the very first time, we were able to actually put cellular ageing on hold.
'These scientists had made an old human cell act young again.
'Two years on, the cells are still dividing 'and yet their telomeres never get any shorter.
' The cells that we were using normally divide up to but no more than about 90 times.
In contrast, the cells into which we put this enzyme, telomerase, did not stop, have continued dividing and have continued dividing and have continued dividing and they're still dividing and some of them have now undergone 400 doublings, so, you can see, that's four or five or six times their normal lifespan.
But they've been behaving so consistently that we're considering them immortal.
Our expectation is that they will never stop dividing.
Unfortunately, the advance with telomerase offer little hope to sufferers of Progeria.
Further research revealed that the disease is a genetic condition not linked to telomere length.
Ory Barnett died in 2006, aged ten.
For ageing research, the work of telomerase was an extraordinary breakthrough.
Though this apparent immortality comes at a price, as Liz Bonnin discovered when she observed the one situation where adult cells naturally produce telomerase of their own accord.
They look like pretty normal cells to me, Tom, what kind of cells are they? - Well, they come from this woman here, Henrietta Lax.
- Right.
And she died back in America, 1951.
- So these are live cells from a dead woman? - Correct.
That sounds very weird, how does that work? These cells are exceptional, they are expressing telomerase.
So these cells can replicate endlessly.
Absolutely.
So are they, as such, immortal? Well, to me they are, they're immortal, they're growing on.
Give me some cells, we'll put telomerase in and they'll live for ever, but there is a drawback.
See, I knew there'd be a catch, what's the problem? To be honest, these are the cells that killed her, these are cancer cells.
What's happening here is, these cells have divided too long.
And as a cell grows and divides, it's going to accumulate damage.
All sort of sources are going to damage the DNA.
And that accumulation of damage is what can lead to cancer.
So if you keep your cell alive longer than it should be, the DNA just gets more and more damaged and it can lead to cancer? Exactly.
And one of the key roles here of telomeres and the telomere shortening and the death of the normal cell in preventing cancer.
Well, it looks like immortality is going to be confined to the lab for a good few years to come.
But there's no question that science has made great inroads into understanding how we might prevent ageing - having good genes, having a very good lifestyle, making sure we don't eat too much.
All these things can help to slow down the ageing process, but we're not really much closer to finding a concrete solution to preventing ageing, which is why some people aren't looking to slow the clock down, but actually to turn it backwards by repairing the damage that ageing has already done to the body.
And wherever there are those who claim to have the power of regeneration, there are others who are willing to believe them.
'And, while the scientists laboriously plod the foothills, 'the charlatans claim to have climbed the mountains 'and seen the view over.
'Ivan Poppof, one time court physician 'to the King of Yugoslavia, 'now, full-time rejuvenationist.
I usually say that I discovered the god in my microscope.
'An embryonic egg flip like this every morning 'for each of his £1,000 clients 'and, because the United States bans such practices as cell therapy, 'the British off-shore islands like the Bahamas 'make an ideal site for dollar earning clinics of this sort.
'Aromatherapy, sleep therapy, Thalassotherapy 'You name it, they do it.
'Poppof, in scientific terms, is a whole body man.
' The women mostly come here for their looks, as the men come for their function.
'Whether or not this treatment 'raises more than the morale is open to doubt.
'At best, what Dr Poppof does 'is to embellish a fairly conventional health farm 'with a lot of pseudo-science.
'It probably doubles the price.
' And pseudo-science seemed to come in many guises, some more gruesome than others.
'Here, to a discreet villa near Montreux, 'come the movie stars and the ambassadors, 'the rich and the distinguished.
'Every Wednesday, they arrive under the conditions of secrecy 'which the Swiss reserve for the especially rich.
'Every Thursday, at least one of the pregnant black sheep is sacrificed 'and her unborn lamb taken from the womb.
'In one of the world's most macabre operations, 'the lamb is meticulously dissected by a team of surgeons, 'each organ is placed in its labelled petri dish.
'In 23 very private rooms, the patients wait, 'like Mrs Zimmerman.
'Now and every four months, 'she is to receive up to 12 syringes, 'one large wine glassful of liquidised thyroid cells from the lamb embryo.
'The theory is that the fresh cells will revitalise her own dead organ.
'They talk about the fountain of youth.
In a word, rejuvenation.
' Unsurprisingly, some scientists were sceptical of such claims.
What in fact you're doing is injecting a beef broth.
You take dead cells and stew them up.
And there's really no evidence that anything that you put in with dead cells has any effect at all on life.
It may help to shorten it, perhaps, I don't know.
But it, at best, it may help you to feel better.
40 years later, there are echoes of this idea in an approach that now genuinely offers hope of regeneration in the field of stem cell research.
In the very earliest stages of life, foetal stem cells form the blank sheet from which all our organs and cells develop.
If we could harness their ability to grow into a multitude of different forms, then the dream of regenerating our worn out organs could become a reality.
Stem cells taken from adult bodies are usually unsuitable, but in the year 2000, scientists found some they could use from an astonishing source.
A teratocarcinoma is the most bizarre kind of tumour that you can possibly imagine.
It's a tumour that actually looks like a little monster.
The word terato means monster and carcinoma of course means cancer.
And these things grow spontaneously inside a woman's ovary out of her eggs, inside a man's testes out of the sperm.
And they grow like little embryos at first, but then they become totally disorganised and so they can be as big as grapefruits, covered in hair with blood vessels and nervous tissue and even teeth inside of them.
And if you poke them, they can actually respond with a nervous reaction to the poke.
And so there's a real question as to whether or not these things are alive or not.
'A teratocarcinoma is a cancer unlike all others.
'Because they grow out of a sperm or egg, 'they contain embryonic stem cells.
'A team of scientists once extracted embryonic stem cells 'from a teratocarcinoma and left them to grow in a petri dish.
'When they next looked, some of the cells were beating in the dish.
'They had turned themselves into heart muscle, kidney, liver and brain cells.
'They have the power of regeneration.
'In Pittsburgh, doctors are taking the first step into the future.
'They are beginning to exploit the potential of embryonic stem cells 'to regenerate our bodies.
'They are using stem cells taken from a teratocarcinoma 'to treat people whose brains have been damaged by a stroke.
' OK, try and lift your hand off the bed.
- 'Don Fitch is one such guinea pig.
' - No.
'The hope was that they'd graft themselves 'onto his existing brain cells and grow, 'helping to reconnect the neural pathways 'that had been damaged by the stroke.
' - How are you doing there, Mr Fitch? Are you OK? - I'm fine, yeah.
- Excellent.
The potential of embryonic stem cell technology is absolutely enormous, because it gives us the idea that we could actually replace tissues and organs as they wear out in human bodies.
That may sound like science fiction, but within a few years, the possibility of creating new organs in the lab was rapidly becoming a reality.
- Hello.
- Hi, there.
Hello.
Hi, there, hello.
- Hi.
- Doris Taylor.
- Hello, Michael Moseley.
Nice to meet you.
Stefan Kran.
- Hello, nice to see you.
You know what I've come to see.
- Yes.
OK, lead me on.
'This is what the excitement is all about, 'it's a newly created heart, 'the result of Dr Taylor's inspired idea.
' Wow! And it is beating.
- It is beating, isn't it? - It is.
It's not my imagination.
How quickly does this happen? - So this is day five - Four.
- Four.
- Day four.
Does it spontaneously start to beat? Yes, yes, absolutely.
Absolutely.
So was it exciting when you first saw it beat? It was one of those yes-moments in life.
It was, you know Yes! It doesn't get any better than this.
'Dr Taylor's team removed a rat's heart 'and washed away all the surface cells, 'leaving a translucent structure made of connective tissue.
'Then, stem cells from another rat were injected 'and, within a few days, miraculously, 'the living heart began to beat.
'In principle, they should be able to do the same thing 'with human organs - hearts, livers, kidneys.
' We think we've opened a door that makes it possible for building virtually any organ.
Any guess as to timescale? I suspect that we could have probably our first organ in a human in about four years.
Wow! That is remarkable.
'If it works in humans, this clearly has the potential 'to extend lifespan by allowing the elderly, 'at least those with enough money, 'to replace their worn out organs with specially engineered new ones.
'However, Dr Taylor's more immediate concern 'is helping those who desperately need a transplant.
A curious idea that, in 200 years' time, you know, maybe when I'm on my fourth heart, my sixth kidney, my third bladder, I could tell my great-great grandchildren how I met Doris and her team 200 years before.
Doris wasn't far off in her predictions - in 2011, her team successfully grew a human heart.
Being able to replace parts of our body as they wear out is an exciting prospect, but there is one thing that we can't yet replace - our minds.
Yet, researchers are becoming increasingly aware of the importance of the mind in the ageing process, not just as something that deteriorates as we grow old, but as a powerful tool that can keep ageing at bay.
The citizens of Loma Linda, in California, have a higher life expectancy than any other community in the United States But their secret isn't a shared ancestry or a restricted diet.
Instead, it's all in the mind.
'Today, Dr Ellsworth Wareham is preparing to perform 'open heart surgery on a patient many years younger than himself.
' Do the patients know that a 92-year-old will be supervising? I would hope not.
I, I personally am sort of less than anxious to let people know my age, because there's a lot of incompetence associated with age.
I think the figure is that 85, at 85 years of age, 50% of people have Alzheimer's.
'Dr Wareham's extraordinary longevity 'may not have anything to do with his genes.
' I don't have a particularly good heredity, three of my grandparents died at 72.
Nobody in my family has lived to be my age.
'The community living in Loma Linda have discovered a secret 'that's much easier to find than any gene.
' Your body is a temple of the holy spirit.
'Marge is a Seventh Day Adventist, 'a religion whose members live between five and ten years longer 'than their fellow citizens.
' Our research indicates that we are in control of at least ten years of extra life just by virtue of the choices that we make or we don't make.
There's been one interesting fact that's been known now for 20 or 30 years.
And that is that people that go to church regularly, whatever faith they have, live longer.
And there is no question about that, the data is very robust.
But it's probably not sitting in the hard pew that does that, there's probably something else.
The support and community offered by religion is thought to help people cope better with stress of all kinds.
Sometimes, it's believed that mental stress causes early ageing and damages your immune system, ultimately shortening life.
Each major stresser of your life is pushing on your organ systems, and these organ systems slowly but surely have effects of all these stressers that are accumulating.
The comfort of religious belief may help keep that stress at bay.
There's many things in life, many stressers that are not controllable, that are not really your choice but you still have to cope with them.
And religion and connection to something higher than oneself, connection to the sacred, connection to a tight-knit religious community allows you to modulate your reactions, your emotions to believe that there is a broader purpose and therefore your body can stay in balance and not be destroyed by those stressers and traumas over time.
'.
.
30 years of which are almost virtually gone.
' But another intriguing study took the power of the mind even further.
In 1979, Dr Ellen Langer conducted a daring experiment by taking a group of elderly volunteers all over the age of 75 back in time.
They were forced to live as if they were 20 years younger, and that meant giving up all outside help and living independently.
'This programme has been brought to you by Curtis, makers of the' We created this environment they were going to be totally immersed in.
It was a timeless retreat that we had transformed, and so, for a full week, they'd be living there as if it was that earlier time.
'See your Ford dealer.
' As soon as we got off the bus, I told them that they were in charge of their suitcases, getting them up to their rooms.
They could move them an inch at a time, they could unpack them right at the bus and take up a shirt at a time.
Just think about the difference in how these people were treated by me, with the assumption that they could do everything, versus treated like when you're a little kid.
And this attitude was going to be maintained right through the experiment.
There was nobody babying them, they were in all ways taking care of themselves as they would have and did, say 20 years earlier.
Ellen was changing the routines and habits they'd built up over the last 20 years and challenging what they'd come to believe was possible, but would their bodies follow their minds? Had her reconstruction been convincing? She'd only run the experiment for one week but at the end of that period, it was crunch time.
Had they changed? We got a difference in their dexterity, a difference in their joint flexibility, their gait, they were able to move faster, they stood taller, their cognitive abilities improved, their blood pressure dropped.
The men put on weight and were objectively judged to look younger.
One man decided he could do without his walking stick.
63% had increased their IQ.
What was even more surprising was that their vision and their hearing improved.
And all of this from them just living as if they were younger for a week's time.
Over the last 45 years, Horizon has documented science's vastly increased understanding of ageing.
Yet, for all the progress, it seems there's still not much it can offer you or I to slow the march of time.
Unless you really fancy chancing your arm on something pretty experimental or, of course, taking a shot of beef broth in the buttocks.
Perhaps, with a bit of mental effort, we can do it ourselves.
So it seems we have more control over the ageing process than we thought and the first thing to do is adapt the right attitude of mind to ageing.
Meanwhile, science promises great things in the near future.
Who knows, they might even crack it in time for me.
But meanwhile, I'll stay young simply by living young.
It might creep up on you, but you only have to look back to spot the changes.
'Do you know that song? We've sung it before.
'Sing it with us this time 'and do the actions as though you were swimming, like Humpty.
' You know, I'd like to think that I've aged or grown old gracefully, but there's no question about it - I have grown old, I've got the evidence to prove it.
It's hard to believe, but it's 45 years since I first started presenting on television.
Since then, my hair's gone grey, and my forehead's so wrinkled, I can screw my hat on.
What I want to know is, does it have to happen or could I stop, or even slow down, the ravages of time? It's a question that has long fascinated amateurs and alchemists alike and, for the last 45 years, Horizon and the BBC have followed as ageing has become the increasing focus of serious scientific studies.
From the earliest days of grappling for answers I think we are miles and miles away from solving the problem of ageing.
We're just right at the very beginning.
.
.
To extravagant promises of longer life.
I would think, by the end of the century, that we will be living to 150 to 200 years.
We've witnessed macabre treatments.
What in fact you are doing is injecting a beef broth.
We have met those who have claimed to have found the ultimate solution.
This was the first discovery that we could actually find a way to slow down the ageing process with a single pill.
And glimpsed a brave new future.
Does it spontaneously start to beat in the end? Yes.
Yes, absolutely.
Wow, that is marvellous.
While some scientists have been driven by the desire to alleviate suffering Having lost my dad to disease, I just want to change the world.
.
.
Others have been spurred on by an all-too-human desire.
Sandy and I have been working on life extension to make the world safe for Durk and Sandy, a couple of gourmets who want to live a long time and stay young.
This is a story we all have a vested interest in, but, after 45 years, how much has science discovered about why we age? And are we any closer to achieving the dream of immortality? We all like to remain young at heart, but wouldn't it be better to just stay young? Perhaps that's why we are all drawn to people who claim they've discovered the elixir of youth, irrespective of how colourful those claims might be.
'Durk Pearson and Sandy Shaw 'have written a bulky manual 'of their life extension techniques 'which has swiftly sold 'more than a million copies in the United States.
' Thank you.
Thank you! I read it every day and use it as, like you would The Bible.
And I'm young and I just want to stay that way so that when I get older, I won't have the problems that people have now.
'Both are in their early forties 'and every day, they consume over 35 different chemical substances 'which they believe are helping to maintain their youth 'and prevent the ravages of age.
'Although neither is a doctor, they did qualify as research scientists, 'and they regularly scan the medical literature 'for news of drugs which might stop them growing old.
This is ornithine.
It's an amino-acid.
It causes the release of a growth hormone by a gland in your brain.
Growth hormone causes you to burn off fat and put on muscle like a teenager with very little exercise.
It also has a very powerful immune stimulant and makes your body better able to fight off infectious diseases and even cancer.
This is vitamin C.
It's an extremely important nutrient to help avert a major form of ageing damage.
In fact, it's so important that the brain and spinal cord have special pumps that bring the concentration of vitamin C up to 100 times that of the general circulation.
This is vitamin B3, niacin.
This is able to reduce the cholesterol in your bloodstream by about 25% within two weeks of when you start taking it.
A lot easier than going on a diet.
We want to live a lot longer.
We'd like to remain young and healthy as long as possible, perhaps even indefinitely.
We and many other people now alive have a very good chance of having an indefinite lifespan, one limited not by ageing or cancer or cardiovascular disease, but rather one limited by accidents, murder and suicide.
Fanciful, maybe, but such claims reflected a real shift in modern attitudes to ageing.
Thank you.
In the post-war era, increasing prosperity and improved healthcare meant many were living longer.
By the 1960s, average life expectancy had increased by nearly ten years in the space of one generation.
The downside was that with longer life came the problems of old age.
Now, just a second, stop.
I think you could walk without it.
No, I can't.
- Why don't you let me take it away for a minute? - Why not? And not just physical disability, but the increased likelihood of a deteriorating mind.
This is essentially an organic deterioration of the brain in which the tissues are breaking down and it's shown clinically as loss of mental powers initially.
The memory goes, this is particularly striking, they can't concentrate.
One doesn't know whether senile dementia is a disease which has, in fact, superimposed on ageing or whether one can look on it simply as the extreme of old age.
And this is what one is trying to find out before one joins the ranks oneself.
The early pioneers in age research were driven by a sense of this pressing social need.
Professor Alex Comfort, who would later become famous for his work on The Joy Of Sex, was one of those determined to find a way of combating the effects of ageing.
One of the first things that every human being learns in childhood is that old people die.
Of course, we can die before we're old, but if we escape all the other hazards and bad luck, we know old age gets us in the end.
In other words, we've got a fixed lifespan and, as more and more of us are surviving to that lifespan, old age accounts for more and more of the work of our medical and social services.
Research money needs now to be spent on alleviating all these special disabilities which go with age.
And I would like to see British biology well in on this attempt to understand ageing and to do something socially and practically useful about it.
And if you wonder whether it's worth it, whether it's worth trying to do something about old age, just you look at the old people around you, the old people you know.
People say old age has its compensations.
Well, maybe it has.
That's very nice, yes.
But you don't ask for compensation unless you've been run over.
Old age is a pretty miserable business.
For Professor Comfort, the first practical step was for scientists to try to get to grips with what controlled this miserable business.
What they are trying to find out is whether there is a single major clock mechanism which determines the progress of age changes and whether it can be slowed.
To find out, in other words, which components in the developmental programme of living are the timekeepers.
The hope was that there was one single dominant factor that acted as a timekeeper.
If scientists could discover that, then maybe they could alter it and enable people to live more healthily for longer.
At the time, there was a broad theory of why we grow old, that ageing was part of a programme in a way in-built in all living things.
'Our voyage through life is programmed, 'just as the holes in the Pianola roll 'dictate the notes to be played and the length of the tune.
'In the same way, the DNA in our cells 'dictates the growth and death both of our organs and of our whole body.
'But, sooner or later, the holes dictate the final chords 'and the roll must run out.
'Professor Bellamy of Cardiff University.
' Many organisms are programmed to live for a set time to reproduce and then immediately die.
The migrating salmon is a good example of this.
It spends most of its life in the sea.
It grows, matures there, it migrates up the river to spawn and then immediately afterwards dies.
So that is the total programme of its life, and natural selection in fact has produced this.
To try and pinpoint a more precise mechanism for ageing, scientists needed to discover more about how the body aged.
The American Institute for Ageing embarked upon an ambitious study, subjecting dedicated volunteers to a battery of tests for over two decades to see what happened to their bodies over time.
'One person who has been coming every year since 1959 'is Mr Young.
'On average, the capacity of the heart to pump 'declines by 33% from age 30 to age 75.
' 174 over 80.
'The lungs do worse than the heart, 'their capacity is down 40%.
'The liver lasts better, 'it loses only 10% of its capacity, 'compensating for the fact that blood flows through it 'much less efficiently.
Put your arms to your side.
'The kidney suffers especially, 'its capacity to filter is down by 44%.
' The results revealed just how complex a process ageing was.
All the organs seem to deteriorate at different rates, making it unlikely that there could be one single mechanism at work.
But what was indisputable was that the body went downhill.
The study suggested that ageing might be caused by the battering our system takes simply in the business of everyday living.
Damage slowly builds up over time.
Service! And we begin to break down.
Professor Comfort likened this to a film running through a projector too many times.
This old film, The Wonderful Hair Restorer, has been shown hundreds of times.
In use, it's accumulated random wear, scratches, breaks, loss of frames where it's been mended.
It's now quite unclear, and prints taken from it will be worse still.
Now, this random damage is what we engineers call noise, it's interference which makes the original information contained in the film harder and harder to read until, really, there is very little left of the film as it was originally made.
Another early expert on ageing, Denham Harman, thought he knew what might be causing the damage and the answer lay not in humans, but in mice.
He reasoned that mice are so short-lived because of what became as the Oxidative Stress Theory of Ageing.
Their high metabolism means mice use lots of oxygen.
The more they breathe, the more it creates dangerous reactive substances called free radicals that damage cells and organs, causing the mice to rapidly age and die.
Denham thought the same principle could be applied to humans and he also suggested a solution, substances that could prevent the damage happening.
We know them today as anti-oxidants.
People began to apply some pretty basic logic to this discovery - if you can increase the anti-oxidants in the body, perhaps through what you ate, then you could stop the free radicals causing damage and thus, slow ageing.
However, where was the proof that this would work? Two brothers thought they had it.
They spent 20 years studying the population of Okinawa, trying to work out why so many people there lived such long and healthy lives.
You walk down the street and there's an elderly lady sweeping outside of her little restaurant, you look at her and you think, "There's a nice 65-year-old lady, "she's probably retired, a part-time job, keeping busy," and then you find out, you know, she's 101.
'The explanation for this extraordinary phenomenon 'begins in the most ordinary of places.
'Like every town in Okinawa, 'the fruit and vegetable shop in Egimi 'lies at the heart of village life.
' 'It's here that Bradley and Craig 'believe the source of the Okinawan miracle can be traced.
' These veggies are a type of a sweet potato.
It's called, in the local dialect it's called "beni-imo.
" And beni-imo, it's a purple sweet potato, isn't it? Oh, look at that purple colour! You can see that purple, the purple really comes out more when you cook it.
The key is to get a lot of vegetables that are, with the very colourful, oranges, like these carrots here, dark greens and yellow vegetables, eryou might think of it as a rainbow diet.
'For the past 20 years, Bradley and Craig have been analysing 'the life-enhancing Okinawan ingredients.
' We got reds here and the tomatoes, the peppers.
You've got green peppers here.
'They've identified a number of crucial properties 'that guard the Okinawans from disease, from the anti-oxidant rich vegetables that protect against cell damage 'to the high quantities of soya proteins.
' We believe that this is playing a part in, in their low rates of hormone-dependent cancers.
'Okinawans have amongst the lowest rates 'of breast and prostate cancer in the world.
If we lived in the West more like the Okinawans, you could probably close down 80% of the coronary care units, one third of the cancer wards and a lot of nursing homes would be out of business, simply because these people are so healthy.
Hmm, he passes the test, this is really good.
Goya chempu! Thank you.
The Okinawan soy and rainbow diet is stuffed full of anti-oxidants.
Its apparent effect in this says, "Yes, the oxidative stress theory of ageing must be correct.
" But, while anti-oxidants have become big business, other studies have found the theory less convincing.
Scientists at the University of Texas investigated oxidative damage in a different rodent - the naked mole-rat, an exceptionally weird-looking creature that seems to have traded beauty for longer life.
If you look at a naked mole-rat, it's a 30-gram animal, the same size as a mouse.
Yet it lives ten times longer than a mouse and it clearly is beating the odds, so we predicted that, given the fact that they live so long, that they would have very low levels of oxidative damage.
So Professor Shelly Buffenstein set out to test the theory, but things didn't pan out as expected.
We found that, even our youngest animals had three to ten times more oxidative damage than a similar physiologically age-matched mouse.
Clearly, it was possible to have high levels of oxidative damage and live a long, healthy life.
But this was not going to go down well.
What Shelly had found would shock colleagues who'd worked in the field for years and threaten the entire anti-oxidant business.
People didn't want to accept what we found because there's too much investment in this area of research, anti-oxidants are a multi-million dollar industry, as you know.
When we tried to publish it in Science, the first review came back, "Well, you guys don't know how to measure this technique, "so that's why you're getting these crazy measurements.
"Send it to a real lab that knows this kind of thing.
" So Shelly repeated the experiment and found that oxidative stress didn't make a difference.
What to me seemed so fascinating is, they've put their little finger up at ageing.
Many people still swear by a diet rich in anti-oxidants, but oxidative stress is really too simple an explanation as to why we age.
But scientists did have evidence that you could slow ageing and it did involve food, but not what you ate, how much you ate.
And once again, mice take centre stage, this time mice on a diet.
This particular mouse is .
.
48 months old.
That's longer than any mouse ever lives who is not on a restrictive diet.
This one has been restricted since about 12 months of age.
Normally, mice never live longer than 36 months.
This means that the ageing process has indeed been retarded by this kind of procedure.
One can slow down ageing.
This is the equivalent in human terms to increasing maximum lifespan from the present level of about 110 years, the longest anybody ever lives, to 150 to 180 years.
This kind of study is, with a high order of probability, directly translatable to human use.
Researchers were uncertain why calorie restriction might work.
Their best guess was that it made the in-built ageing programme run slower.
For some, the evidence proved too tempting a prospect to pass up, including Dr Walford.
'For a man in his sixties who fasts three days a week, 'Roy Walford seems to be living proof 'that eating less but eating well keeps you fit and young.
' My own technique for extending maximum lifespan includes a programme that I call "under-nutrition without malnutrition.
" That means lowering the caloric intake but keeping the nutritive value of your food very high and this, if one translates the animal data into human use, should extend lifespan by a very substantial amount, depending on what age you are when you begin that kind of a programme.
Despite his certainty, Walford was taking a leap of faith and it would take a very hungry lifetime to see if the bet paid off.
But that hasn't stopped a host of others giving it a go.
In 2009, Michael Moseley went to meet one of them to see what effect 16 years of living on just 1,600 calories a day might have had.
- Hello.
- Welcome, hi! - Hello, very nice to see you.
- First impressions - very youthful, I have to say.
- Oh, thank you.
Very youthful.
Can I just look at your face? Me? I thought you meant the house.
No, I think you, good, very good.
'Calorie restriction isn't simply about eating less.
'Dave eats salad on an industrial scale 'to get all the vitamins and minerals he needs.
'At 51, he certainly looks good on the outside.
'But I wanted to know what was going on inside.
'A series of tests would compare our bodies 'and determine who was biologically younger.
' Could you sit down and sit back? HE LAUGHS 'How embarrassing, I hadn't realised how competitive I am.
' HE COUGHS - Are you going to pass out there, mate? - I was going to pass out, let me tell you.
'Finally, our skin was analysed 'by cosmetic surgeon Mr Jaya Prakash.
' Right, that's better.
Oh, what a big funny nose I have.
His skin is better than mine.
According to these graphs, his skin is marginally better.
- Yeah, yeah, yeah.
- Marginally.
- Marginally.
Yes, how old do you think we are? - If you want me to guess - Yes.
Dave would be 35.
Mmm-hmm, and how old do you think I am? HE LAUGHS You reckon I'm 50 and he's 35? - Yeah.
- OK.
Yeah, that's right, that suits me.
OK.
I am 51, and he is 51.
- We're actually the same age within a month.
- Really? Well, he may look great but most of us, and me for one, would really baulk at the idea of a lifetime of salad.
But one scientist discovered how calorie restriction worked and that it could work irrespective of what you eat, and then everyone sat up to take notice.
The secret is in our genes, in the genetic makeup within our DNA.
I know about a dozen people voluntarily restricting their food so that they're for the most part hungry during the day, in the hopes that that will extend their lifespan, but you have to be hungry for this to work.
And I tried it for about a week and it meant eating baby food and just a few vegetables, and I felt hungry all the time and I thought, "If this is going to be my life for the next hundred years, I don't want it.
" David Sinclair wanted to find out how calorie restriction worked to see if he could create its effects without starving himself.
He began by studying yeast, but it wasn't what the yeast ate that concerned him.
Rather, it was their genes.
The organisms that I'm particularly excited about are yeast cells.
These are yeasts that you put in your bread and your beer, but actually, they have a lifespan of about a week and the goal, about 15 years ago, was to find out why do they age and what can we do about it? And what we were looking for were genes that, if you delete them or you add an extra copy of them, that they live longer.
We found a set of genes that do that.
They're called the sirtuin genes, and really what was very exciting was that just adding one extra copy of a gene called Sir2 could greatly extend the lifespan of those yeast about 30%.
David had found a gene in the yeast that seemed to directly influence ageing, an astonishing discovery.
So he removed the gene to see what happened when he then restricted what the yeast fed on.
What the team discovered was that, when this gene wasn't there any more in the yeast cells, they didn't respond to the diet calorie restriction, they didn't live longer, so we knew immediately that this gene, maybe others, were really important for this diet to work.
What was a really amazing discovery was to realise that this diet and these genes were part of the same system and that was a real breakthrough.
David had discovered why calorie restriction worked.
He now wanted to see if he could get the benefit without going hungry.
After ten years, he found a molecule called resveratrol that seemed to mimic the effect of the diet.
The amazing thing about this molecule is, when you feed it to life forms, so a yeast cell or a worm or a fly, even a mouse that's obese, they live longer and they're much healthier.
And this was the first discovery that we could actually find a way to slow down the ageing process with a single pill.
This could be the ultimate dream - an anti-ageing pill.
Glaxo-Smith-Klein paid 720 million for David's company and, while it's too early to know if resveratrol works in humans, David isn't waiting to find out.
I'm a scientist.
Occasionally, I experiment on myself as well and so I started taking resveratrol as soon as we had tested it on yeast cells.
Now, looking back, that was a little mad.
We didn't know if it was toxic, might have even caused cancer.
Fortunately, we now know that resveratrol is, as far as we can tell, relatively safe.
My wife started taking resveratrol, my family does.
Now, I don't endorse it, it's still an investigational molecule, but I felt that the signs were strong enough for me to take that risk and I know what's going to happen if I don't take it.
The ability to just pop a pill to stop the ageing process sounds too good to be true, and at the moment it still is, but what the work did show was how important our genes are in the ageing process, and our increased ability to understand our genetic makeup has revolutionised our understanding of how we grow old.
This expanding knowledge of genetics has turned communities where people make a habit of living long lives into superb laboratories for ageing research.
In New York, Professor Nir Barzilai studied a Jewish community full of centenarians to work out what role their genes played in helping so many of them reach a hundred.
I think the ageing can be redefined after you see so many centenarians like I do, and I'm really jealous of them.
They might look old to you, but you see that their life is so meaningful.
- Hi, Grandma, it's good to see you again.
- My darling, I'm so glad you came.
The old man with the beard is my baby grandson.
Ria Tauba is 102 and part of Nir's study.
The chances of living to a hundred are only one in 10,000.
Cheers, that's great.
The question for Nir was how much of their longevity was down to genes and how much could be about lifestyle.
- Are you going to have some lox, Grandma? - What could be bad? What could be bad? There you go.
Eat like this, and you live to 102.
So his team conducted physical and cognitive assessments and asked the 500 centenarians a range of lifestyle questions.
Did you eat yoghurt all your life? You know, were you a vegetarian? What was your interaction with the environment? And I think the surprising thing for us is that we don't have yoghurt eating, we don't have a single vegetarian.
We have just one person who was an athlete.
Nir gathered their blood samples and prepared to map their genes.
After five years, Nir finally had some results.
He found a gene key to longevity and has since found two more.
Two of those genes seem to be relevant to cholesterol.
Basically, they increase the good cholesterol in a significant way.
There is no drug currently that does it so effectively.
And another gene seemed to be very important as preventing diabetes.
For most of us, how much we eat and exercise is key to how healthy we are and to how long we live, but there was something rather shocking about these centenarians.
30% smoked two packs of cigarettes for more than 40 years.
Because our centenarians have longevity genes, they are protected against many of the effects of the environment, that's why they do whatever they want to do and they get there anyhow.
Those key genes apparently overpower the effects of diet and lifestyle and leave a wonderful legacy for the next generation.
So, Grandma, what are your plans for your next birthday? The children of these Jewish centenarians are 20 times more likely than the general population to live to be a hundred.
- If you have a nice guy for me, I'll go on a date.
- OK.
THEY CHUCKLE For the rest of us, what our genes might have in store is a lottery.
There's no way of knowing whether we have long life in our DNA.
But is there anything we can do to change the odds in our favour? Ageing and death are both programmed into our genes.
It doesn't mean it always has to be that way.
If we can figure out what the programme is, then we can try to fix the programme and to stop ageing from taking place.
Scientists searched for ways of fixing the programme by experimenting with selective breeding.
Not on humans! Instead, they chose something much shorter lived - they chose the common fruit fly.
A team at the university of California devised a simple breeding programme in which only eggs from older flies were allowed to survive while those from younger flies were destroyed.
The essence of the experiment is to say to the fruit flies, "OK, you don't get to reproduce until you're older.
" And that means you have to survive until you're older, and it means also when you're older, you have to have the physiological ability to reproduce when you're older.
And natural selection screens the flies under those conditions for postponed ageing automatically.
'The only eggs allowed to hatch are those with the genes for long life.
'This single experiment has been going on for over two decades.
'Over hundreds of generations of selective breeding, 'the fruit flies have slowly doubled their lifespan.
'But the most remarkable thing about this experiment 'is what extreme old age does to these flies.
' The much longer-lived fruit fly turns out to be very different from what you might imagine.
These fruit flies that have increased lifespan are far more athletic than normal fruit flies, they fly for much longer, walk for much longer.
They are vastly more resistant to a variety of stresses, they are very robust in that sense and they certainly set to enjoying life, at least from a sexual standpoint.
A longer life and more sex, sounds like a win/win situation for fruit flies.
But, really, could we do that with humans? Use selective breeding to lengthen our lives? Think of the ethical nightmare of that.
So if we couldn't breed for immortality, could we still find the answer somewhere else, deep within ourselves? Scientists working in another area of ageing research thought they had it.
Only this time, the insight came from not studying the very old, but the tragic cause of ageing in the very young.
In 2000, Horizon met Ory Barnett, a young boy suffering from the rare disease Progeria, which causes early ageing.
Although only three, Aury already had wrinkles, stiff joints and thinning hair.
Sufferers often go onto develop arthritis and heart disease and most will die of old age whilst still in their teens.
I thought that he was just a perfect little boy and to find out that he had, you know, things wrong with him, it was just, it was very upsetting.
'Scientists now believe they can explain 'why these children age so suddenly 'and this is offering clues to how we all age.
'They have discovered that there is a time bomb inside our cells 'that causes them to stop dividing 'and, for Progeric children, 'the fuse on this timebomb is the wrong length.
'Inside every cell in our body, 'at the end of our chromosomes, 'is a piece of DNA called a telomere.
'It stops the DNA from fraying as it divides.
'But, every time a cell divides, the telomere gets shorter.
'Eventually, the telomere shortens to a critical length 'and the next time the cell divides, 'the telomere can no longer protect the fraying DNA and the cell dies.
'What scientists now know is that Progeric children 'begin their lives with unnaturally short telomeres 'and that is why they age so quickly.
' If the shortening of the telomeres could be slowed or reversed then, perhaps, there was a hope of a cure for Progeria and a chance of influencing the way we age.
Scientists knew that an enzyme called telomerase could repair telomeres.
Researchers at the university of Texas inserted the gene for telomerase into skin cells taken from an old man and waited to see if they started producing the enzyme.
And I can remember the postbox bringing me the gel, this is a piece of film showing that these cells had telomeres.
And I told the postbox, "Remember this moment," because it was one of those, it wasn't one of these eureka sort of things but it was almost like that, because we were sitting there and I realised, for the very first time, we were able to actually put cellular ageing on hold.
'These scientists had made an old human cell act young again.
'Two years on, the cells are still dividing 'and yet their telomeres never get any shorter.
' The cells that we were using normally divide up to but no more than about 90 times.
In contrast, the cells into which we put this enzyme, telomerase, did not stop, have continued dividing and have continued dividing and have continued dividing and they're still dividing and some of them have now undergone 400 doublings, so, you can see, that's four or five or six times their normal lifespan.
But they've been behaving so consistently that we're considering them immortal.
Our expectation is that they will never stop dividing.
Unfortunately, the advance with telomerase offer little hope to sufferers of Progeria.
Further research revealed that the disease is a genetic condition not linked to telomere length.
Ory Barnett died in 2006, aged ten.
For ageing research, the work of telomerase was an extraordinary breakthrough.
Though this apparent immortality comes at a price, as Liz Bonnin discovered when she observed the one situation where adult cells naturally produce telomerase of their own accord.
They look like pretty normal cells to me, Tom, what kind of cells are they? - Well, they come from this woman here, Henrietta Lax.
- Right.
And she died back in America, 1951.
- So these are live cells from a dead woman? - Correct.
That sounds very weird, how does that work? These cells are exceptional, they are expressing telomerase.
So these cells can replicate endlessly.
Absolutely.
So are they, as such, immortal? Well, to me they are, they're immortal, they're growing on.
Give me some cells, we'll put telomerase in and they'll live for ever, but there is a drawback.
See, I knew there'd be a catch, what's the problem? To be honest, these are the cells that killed her, these are cancer cells.
What's happening here is, these cells have divided too long.
And as a cell grows and divides, it's going to accumulate damage.
All sort of sources are going to damage the DNA.
And that accumulation of damage is what can lead to cancer.
So if you keep your cell alive longer than it should be, the DNA just gets more and more damaged and it can lead to cancer? Exactly.
And one of the key roles here of telomeres and the telomere shortening and the death of the normal cell in preventing cancer.
Well, it looks like immortality is going to be confined to the lab for a good few years to come.
But there's no question that science has made great inroads into understanding how we might prevent ageing - having good genes, having a very good lifestyle, making sure we don't eat too much.
All these things can help to slow down the ageing process, but we're not really much closer to finding a concrete solution to preventing ageing, which is why some people aren't looking to slow the clock down, but actually to turn it backwards by repairing the damage that ageing has already done to the body.
And wherever there are those who claim to have the power of regeneration, there are others who are willing to believe them.
'And, while the scientists laboriously plod the foothills, 'the charlatans claim to have climbed the mountains 'and seen the view over.
'Ivan Poppof, one time court physician 'to the King of Yugoslavia, 'now, full-time rejuvenationist.
I usually say that I discovered the god in my microscope.
'An embryonic egg flip like this every morning 'for each of his £1,000 clients 'and, because the United States bans such practices as cell therapy, 'the British off-shore islands like the Bahamas 'make an ideal site for dollar earning clinics of this sort.
'Aromatherapy, sleep therapy, Thalassotherapy 'You name it, they do it.
'Poppof, in scientific terms, is a whole body man.
' The women mostly come here for their looks, as the men come for their function.
'Whether or not this treatment 'raises more than the morale is open to doubt.
'At best, what Dr Poppof does 'is to embellish a fairly conventional health farm 'with a lot of pseudo-science.
'It probably doubles the price.
' And pseudo-science seemed to come in many guises, some more gruesome than others.
'Here, to a discreet villa near Montreux, 'come the movie stars and the ambassadors, 'the rich and the distinguished.
'Every Wednesday, they arrive under the conditions of secrecy 'which the Swiss reserve for the especially rich.
'Every Thursday, at least one of the pregnant black sheep is sacrificed 'and her unborn lamb taken from the womb.
'In one of the world's most macabre operations, 'the lamb is meticulously dissected by a team of surgeons, 'each organ is placed in its labelled petri dish.
'In 23 very private rooms, the patients wait, 'like Mrs Zimmerman.
'Now and every four months, 'she is to receive up to 12 syringes, 'one large wine glassful of liquidised thyroid cells from the lamb embryo.
'The theory is that the fresh cells will revitalise her own dead organ.
'They talk about the fountain of youth.
In a word, rejuvenation.
' Unsurprisingly, some scientists were sceptical of such claims.
What in fact you're doing is injecting a beef broth.
You take dead cells and stew them up.
And there's really no evidence that anything that you put in with dead cells has any effect at all on life.
It may help to shorten it, perhaps, I don't know.
But it, at best, it may help you to feel better.
40 years later, there are echoes of this idea in an approach that now genuinely offers hope of regeneration in the field of stem cell research.
In the very earliest stages of life, foetal stem cells form the blank sheet from which all our organs and cells develop.
If we could harness their ability to grow into a multitude of different forms, then the dream of regenerating our worn out organs could become a reality.
Stem cells taken from adult bodies are usually unsuitable, but in the year 2000, scientists found some they could use from an astonishing source.
A teratocarcinoma is the most bizarre kind of tumour that you can possibly imagine.
It's a tumour that actually looks like a little monster.
The word terato means monster and carcinoma of course means cancer.
And these things grow spontaneously inside a woman's ovary out of her eggs, inside a man's testes out of the sperm.
And they grow like little embryos at first, but then they become totally disorganised and so they can be as big as grapefruits, covered in hair with blood vessels and nervous tissue and even teeth inside of them.
And if you poke them, they can actually respond with a nervous reaction to the poke.
And so there's a real question as to whether or not these things are alive or not.
'A teratocarcinoma is a cancer unlike all others.
'Because they grow out of a sperm or egg, 'they contain embryonic stem cells.
'A team of scientists once extracted embryonic stem cells 'from a teratocarcinoma and left them to grow in a petri dish.
'When they next looked, some of the cells were beating in the dish.
'They had turned themselves into heart muscle, kidney, liver and brain cells.
'They have the power of regeneration.
'In Pittsburgh, doctors are taking the first step into the future.
'They are beginning to exploit the potential of embryonic stem cells 'to regenerate our bodies.
'They are using stem cells taken from a teratocarcinoma 'to treat people whose brains have been damaged by a stroke.
' OK, try and lift your hand off the bed.
- 'Don Fitch is one such guinea pig.
' - No.
'The hope was that they'd graft themselves 'onto his existing brain cells and grow, 'helping to reconnect the neural pathways 'that had been damaged by the stroke.
' - How are you doing there, Mr Fitch? Are you OK? - I'm fine, yeah.
- Excellent.
The potential of embryonic stem cell technology is absolutely enormous, because it gives us the idea that we could actually replace tissues and organs as they wear out in human bodies.
That may sound like science fiction, but within a few years, the possibility of creating new organs in the lab was rapidly becoming a reality.
- Hello.
- Hi, there.
Hello.
Hi, there, hello.
- Hi.
- Doris Taylor.
- Hello, Michael Moseley.
Nice to meet you.
Stefan Kran.
- Hello, nice to see you.
You know what I've come to see.
- Yes.
OK, lead me on.
'This is what the excitement is all about, 'it's a newly created heart, 'the result of Dr Taylor's inspired idea.
' Wow! And it is beating.
- It is beating, isn't it? - It is.
It's not my imagination.
How quickly does this happen? - So this is day five - Four.
- Four.
- Day four.
Does it spontaneously start to beat? Yes, yes, absolutely.
Absolutely.
So was it exciting when you first saw it beat? It was one of those yes-moments in life.
It was, you know Yes! It doesn't get any better than this.
'Dr Taylor's team removed a rat's heart 'and washed away all the surface cells, 'leaving a translucent structure made of connective tissue.
'Then, stem cells from another rat were injected 'and, within a few days, miraculously, 'the living heart began to beat.
'In principle, they should be able to do the same thing 'with human organs - hearts, livers, kidneys.
' We think we've opened a door that makes it possible for building virtually any organ.
Any guess as to timescale? I suspect that we could have probably our first organ in a human in about four years.
Wow! That is remarkable.
'If it works in humans, this clearly has the potential 'to extend lifespan by allowing the elderly, 'at least those with enough money, 'to replace their worn out organs with specially engineered new ones.
'However, Dr Taylor's more immediate concern 'is helping those who desperately need a transplant.
A curious idea that, in 200 years' time, you know, maybe when I'm on my fourth heart, my sixth kidney, my third bladder, I could tell my great-great grandchildren how I met Doris and her team 200 years before.
Doris wasn't far off in her predictions - in 2011, her team successfully grew a human heart.
Being able to replace parts of our body as they wear out is an exciting prospect, but there is one thing that we can't yet replace - our minds.
Yet, researchers are becoming increasingly aware of the importance of the mind in the ageing process, not just as something that deteriorates as we grow old, but as a powerful tool that can keep ageing at bay.
The citizens of Loma Linda, in California, have a higher life expectancy than any other community in the United States But their secret isn't a shared ancestry or a restricted diet.
Instead, it's all in the mind.
'Today, Dr Ellsworth Wareham is preparing to perform 'open heart surgery on a patient many years younger than himself.
' Do the patients know that a 92-year-old will be supervising? I would hope not.
I, I personally am sort of less than anxious to let people know my age, because there's a lot of incompetence associated with age.
I think the figure is that 85, at 85 years of age, 50% of people have Alzheimer's.
'Dr Wareham's extraordinary longevity 'may not have anything to do with his genes.
' I don't have a particularly good heredity, three of my grandparents died at 72.
Nobody in my family has lived to be my age.
'The community living in Loma Linda have discovered a secret 'that's much easier to find than any gene.
' Your body is a temple of the holy spirit.
'Marge is a Seventh Day Adventist, 'a religion whose members live between five and ten years longer 'than their fellow citizens.
' Our research indicates that we are in control of at least ten years of extra life just by virtue of the choices that we make or we don't make.
There's been one interesting fact that's been known now for 20 or 30 years.
And that is that people that go to church regularly, whatever faith they have, live longer.
And there is no question about that, the data is very robust.
But it's probably not sitting in the hard pew that does that, there's probably something else.
The support and community offered by religion is thought to help people cope better with stress of all kinds.
Sometimes, it's believed that mental stress causes early ageing and damages your immune system, ultimately shortening life.
Each major stresser of your life is pushing on your organ systems, and these organ systems slowly but surely have effects of all these stressers that are accumulating.
The comfort of religious belief may help keep that stress at bay.
There's many things in life, many stressers that are not controllable, that are not really your choice but you still have to cope with them.
And religion and connection to something higher than oneself, connection to the sacred, connection to a tight-knit religious community allows you to modulate your reactions, your emotions to believe that there is a broader purpose and therefore your body can stay in balance and not be destroyed by those stressers and traumas over time.
'.
.
30 years of which are almost virtually gone.
' But another intriguing study took the power of the mind even further.
In 1979, Dr Ellen Langer conducted a daring experiment by taking a group of elderly volunteers all over the age of 75 back in time.
They were forced to live as if they were 20 years younger, and that meant giving up all outside help and living independently.
'This programme has been brought to you by Curtis, makers of the' We created this environment they were going to be totally immersed in.
It was a timeless retreat that we had transformed, and so, for a full week, they'd be living there as if it was that earlier time.
'See your Ford dealer.
' As soon as we got off the bus, I told them that they were in charge of their suitcases, getting them up to their rooms.
They could move them an inch at a time, they could unpack them right at the bus and take up a shirt at a time.
Just think about the difference in how these people were treated by me, with the assumption that they could do everything, versus treated like when you're a little kid.
And this attitude was going to be maintained right through the experiment.
There was nobody babying them, they were in all ways taking care of themselves as they would have and did, say 20 years earlier.
Ellen was changing the routines and habits they'd built up over the last 20 years and challenging what they'd come to believe was possible, but would their bodies follow their minds? Had her reconstruction been convincing? She'd only run the experiment for one week but at the end of that period, it was crunch time.
Had they changed? We got a difference in their dexterity, a difference in their joint flexibility, their gait, they were able to move faster, they stood taller, their cognitive abilities improved, their blood pressure dropped.
The men put on weight and were objectively judged to look younger.
One man decided he could do without his walking stick.
63% had increased their IQ.
What was even more surprising was that their vision and their hearing improved.
And all of this from them just living as if they were younger for a week's time.
Over the last 45 years, Horizon has documented science's vastly increased understanding of ageing.
Yet, for all the progress, it seems there's still not much it can offer you or I to slow the march of time.
Unless you really fancy chancing your arm on something pretty experimental or, of course, taking a shot of beef broth in the buttocks.
Perhaps, with a bit of mental effort, we can do it ourselves.
So it seems we have more control over the ageing process than we thought and the first thing to do is adapt the right attitude of mind to ageing.
Meanwhile, science promises great things in the near future.
Who knows, they might even crack it in time for me.
But meanwhile, I'll stay young simply by living young.