"The elixir of youth, a potion that can hold back the hands of time, once seemed impossible." "Cver the years, many have claimed to have found such a potion." "None have." "'TiI now." "At the start of the 21st Century, we are at last learning the secrets of how to build a longer lasting human." "The search for the elixir of youth starts inside the cell." "Here, rogue elements cause most of the damage that we call ageing." "If we can reduce this damage, we might slow the seemingly inevitable decline to old age." "Scientists have recently shown that it's possible to double the lifespan of an animal." "Here was a perfectly normal animal which just simply lived twice as long as its genetic counterparts." "And experts in ageing now believe that human lifespan can also be doubled, to well over a 150 years." "I think 150 years is really a conservative estimate." "I wouldn't be surprised if it's not substantially longer." "Cver the Iast century," "life expectancy has almost doubled." "We can expect to live a good 30 years longer than our great grandparents." "To double our current lifespan, molecular biologists are manipulating our cells." "For the first time, they have proof that delaying ageing is possible." "But not everyone thinks it should be done." "If you talk to any molecular geneticist in the world today, they will have to admit to you that this could happen." "They may hate it, with all of their heart they may hate it, but they have to admit that the technology exists for this to happen." "Drugs that have doubled the lifespan of animals may soon be tested on humans." "But are we ready for the changes a true elixir of youth would bring?" "Long ago, some animals learnt the trick of living a very long time." "The hydra, for example." "This microscopic fresh water creature looks unremarkable, but the hydra possesses one impressive ability," "time passes, but its youth and vigour never decline." "Strangest of all, when researchers break hydras down to their very cells, something extraordinary occurs." "In a matter of hours, out of the mass of cells rise fully grown hydras." "Hydras, however, are very simple." "We are not." "The human body is made up from 100 million million million different cells." "Some are manufactured continuously." "A 170 billion red cells form daily to carry oxygen." "10 billion white cells form to fight disease." "Cthers, Iike the cells of the nose and ear, renew themselves so vigorously, they just keep on growing all life long." "But, eventually, something goes wrong." "Cur cells start to feign, our skin wrinkles, our hair greys, and eye-sight fades." "Is there anything we can do to turn back the clock?" "Leading choreographer, gillian Lynne, doing an impressivejob at staying young." "She keeps age at bay through sheer hard work." "She exercises for three hours everyday." "It's hard to believe she's 75 years old, and can still go toe to toe with the 20 year olds." "The difficulty about trying to fight the ageing process is that we're told that from the age of 25 the body starts to deteriorate." "I can't say that it's easy, it isn't, and it's mostly painful." "If you want to remain at all young, there are no shortcuts." "well, as you see," "I've done quite well in keeping age at bay by exercising." "But there's one bit of me I'm afraid I can't control at all," "look at this, the famous skin test." "slow like a tortoise." "And the effects of ageing are not just superficial." "These days, gillian can only dance thanks to artificial hip joints." "regular exercise will help you live a little longer, but keeping forever young requires something more." "Cne man who claims he does possess that extra something is Doctor Ron Livesy." "He runs a private anti-ageing clinic in New York." "He believes his treatment programme will slow down, even reverse the ageing process." "He's in his mid-50s and he's on it himself." "I've noticed many benefits over the past five years." "I've regained my lean body mass and" "lost approximately 60Ibs of abdominal fat." "My immune system is clearly working much better, because I no Ionger get frequent colds and no Ionger require sick days from work." "My bad cholesterol is now normal, my good cholesterol has gone from being low to a quite healthy range." "Diane GiIman is one of Doctor Livesy's clients." "At 56, she has also decided not to give in to age." "I was always the kind of person that believed you could fight mother nature." "If you ate right, if you exercised right, if you got enough sleep, and at about 50 years old I just hit a brick wall." "Mother nature said, aha, those aren't the plans I have for you." "I couldn't fight all of the things that were happening to me, many of which I didn't even understand were about ageing." "horrible back pains, terrible pains and cramps in my legs." "Diane's main weapon in the war against ageing is called human growth hormone." "whilst we're going through childhood and adolescence, our bodies are churning out large amounts of growth hormone." "It helps build muscle and repair tissues." "At about the age of 25, levels peak, then start to drop off." "By the time we reach old age, our bodies are producing very little." "Diane is injecting herself with just enough growth hormone to push her levels back to those she had when she was 25." "This requires two shots a day, at a cost of over $1,000 a month." "I will never forget the first day that" "I injected myself with human growth hormone." "I felt like a watch." "If you have a watch where you can see all the cogs and mechanisms working on the back, it was like everything was working and going in one direction, which everything came to a halt" "and then started to go in another direction." "It really has turned back the hands of time." "Diane's daily injections have helped transform one symptom of ageing, removing those extra pounds from her waistline." "The short term slimming effect of growth hormone is well known to doctors." "This patient has had a brain tumour." "It stopped him producing growth hormone." "He is being given doses of artificial growth hormone, and he's experiencing the same loss of fat as Diane." "He's in the hands of hormone expert, Professor Stephen ShaIet." "It does have a profound effect, the amount of fat on their body is dramatically reduced, and the amount of muscle is significantly increased." "This scan is of the cross section of a middle aged man." "It shows light areas of fat, not only round the belly, but also inside." "Thick layers cover the major organs." "After six months of growth hormone, much of the fat has gone." "could it be that growth hormone is the wonder drug, the key to building a Iong living human?" "I think it's unfortunate that one of the tags that growth hormone was given was the elixir of youth." "There is no objective evidence that growth hormone treatment prolongs life." "And there is a risk in using growth hormone when you're middle aged." "Cancer." "Growth hormone could encourage cancer cells to spread more rapidly." "The risks of an individual developing cancer, far outweigh any potential benefits, so I think it's extremely unwise, and a road that we should not go down." "I weighed the risks and the conclusion I came to was, you know what, I got nothing to lose here." "I've got everything to gain." "And so far, so good." "I'm up for the challenge." "I would Iike to see what the next 100 years brings for me." "while it is extremely unlikely that Diane will live to over a 150, there are some animals that can." "animals like Harriet." "She is over 170 years old, which makes her one of the oldest creatures on the planet." "She was born before Victoria was Queen." "She was already five years old when charles Darwin paid her a visit on his historic voyage to the galapagos islands." "Harriet may not be immortal, but she's living proof that some animals are much more successful than we are at resisting ageing." "The question is, how?" "clues lie in a shared ancestor, one who lived a Iong, long time ago." "Four billion years ago, when life started on this planet," "the world looked very different." "volcanoes were active, belching in to the atmosphere, a mixture of carbon dioxide and sulphur." "These gases would have coloured the sky red." "blue green algae dominated the planet." "They used the energy from the sun and combined it with the gases in the atmosphere to make food." "But, as they spread over the planet, these algae produced this new gas:" "oxygen." "levels in the atmosphere slowly rose from almost nothing to over 20%, and turned the sky blue." "But for early life, oxygen was a major hazard, because oxygen is a highly explosive, reactive gas." "Cne man who knows just how dangerous it can be, is pyrotechnics specialist, malcolm Armstrong." "Cxygen is one of the most reactive gases on planet earth." "chemical explosions require two components, fuel and oxygen." "Here, malcolm fills a tube with a little fuel and a little oxygen." "The effect is underwhelming." "Now, keep the same amount of fuel and increase the oxygen." "I've put 300 times the amount of oxygen in here." "And it becomes a very different story." "Cxygen is dangerous." "Two and a half billion years ago, oxygen would have killed most of the life forms it came in contact with." "But one microbe found a way of harnessing the explosive power of this gas." "It's called a mitochondrion." "Each mitochondrion became a miniature power station." "What followed next was one of the most important steps in the history of Iife on this planet, and is perhaps the most vital clue of all as to why we age." "Two of the many single cells joined forces." "The tiny power plant, one of the mitochondria, was absorbed in to another primitive cell." "Life on earth changed forever." "Today, mitochondria live inside the cells of every living creature." "An expert in molecular biology," "John Burn, is fascinated by our relationship with this early organism." "Most people had never heard the word mitochondria, and yet the cells in my brain that are thinking of these words, and the cells in my tongue that are helping to form them, get their energy from mitochondria." "Every living creature on this planet has mitochondria within their cells." "They are the power plants that fuel all life, including us." "They're like millions of tiny batteries, and when it was first suggested that mitochondria might once have been free living bacteria, it seemed almost impossible to believe." "These ancient bacteria really are everywhere." "For exampIe, in the tails of sperm." "A new laser scanning microscope allows us to see, for the first time, how individual sperm are powered by mitochondria." "They are the glowing section in the tail that propel the sperm in their frantic journey to fertilise the egg." "And it's the same story with eggs." "They are so densely packed with mitochondria, that under the laser they glow, Iike the sun." "Mitochondria are the power sources that will drive the growth spurt to build a new human." "Cur every movement is powered by them." "And our every breath brings them the oxygen they need." "But there's a heavy cost." "With every breath we age." "Life giving oxygen is slowly killing us." "Because oxygen isn'tjust explosive, it's corrosive." "When oxygen touches pure iron it starts a chemical reaction that turns it to rust." "This nail turned rusty by exposure to oxygen has been eaten away." "And if oxygen can do this to metal.." "just imagine what it can do to your body." "It seems almost unbelievable that we're sitting here in 20% oxygen, breathing it, depending on it, and yet that same oxygen inside our body is actually doing damage, it's like rusting us from the inside." "If you think about it, the atmosphere should probably have a health warning." "The trouble is that it's notjust oxygen that's corrosive." "So are its by-products." "Inside the mitochondria, most of the oxygen we breath is transformed in to life giving energy." "But not all." "Some oxygen degrades in to particles called free radicals." "The trade-off, more power but more damage, intrigues biologists like Gordon Lithgow." "Mitochondria is really like an alien invader." "It's a bit of a pact with the devil." "We get from the mitochondria lots of cheap free energy, but also it's possible we get ageing." "The mitochondria are a bit like a nuclear power station in your back garden," "lots of cheap, free energy, but highly toxic by-products that have to be managed." "Cne released, free radicals can damage any part of any cell in the body." "Worst of all, they strike at the genes at the heart of every cell." "So what's the proof that this battering inside leads to the decay we know as ageing?" "Forensic pathologist, Dick Shepherd, sees the sign of oxygen and free radical damage almost every working day." "We see damage caused by oxygen in almost everybody that we examine." "It's present at a cellular level, but we see it with the naked eye in the brain and the heart and the lungs." "The lungs are the first point at which the atmospheric oxygen reaches in to the body," "passes through tiny little spaces that are lined by single layers of cells in to the blood stream." "But, of course, these cells, although they are there to transport the oxygen, are also particularly vulnerable." "And this is normal lung, smooth surface, big blood vessel running down the middle of it." "There are no holes, there are no abnormalities." "A lifetime of exposure to pollutants like smoking, will change that." "Tobacco smoke dramatically increases the production of free radicals in the body," "leading to cancer and other lung disorders." "In this lung, the damage is obvious." "The damage done by free radicals can also be seen in other organs." "cardiovascular disease, that's disease of the heart and the blood vessels is the number one killer throughout the world." "As it circulates, blood carries oxygen and free radicals around the body." "Cver time, they can damage artery walls." "Combined with cholesterol, this leads to furring up of important blood vessels." "This is the inside of the aorta, the biggest blood vessel of the body." "Athin, smooth tube, a perfect vessel for the transport of blood." "And this is what an aorta that's got severe fatty deposits looks like." "The fat has been affected by the oxidation and formed this rancid butter which has caused weakening of the wall." "The fatty deposition starts in our 20s, but it may be 40 years or so until the effects become obvious to the individual." "The brain is about 2% of the weight of the human body, but consumes about 20% of the oxygen." "And we're all worried about the effects of dementia as we get older, and we do know that the brain cells are particularly susceptible to the toxic effects of oxygen." "A young brain glows with huge numbers of mitochondria." "But as time goes by, the free radicals produced by the enormous energy demands of the brain, begin to kill the mitochondria." "Cne by one, the batteries fail." "And so does our brain." "Memory becomes impaired, and thinking becomes confused." "When we dissect brains we can sometimes see those changes." "cid brains show extensive signs of free radical damage." "In some brains, Iike this one, the damage is greatest amongst the cells that control movement." "normal brains have a healthy dark line of these specialist cells, but in the brain on the right, the dark cells are no Ionger visible." "They have been destroyed by the products of oxygen." "Given that we know the effects of oxygen, it's not a surprise that we age or we grow old." "What is surprising though is that we actually live so long and remain so healthy." "The link between oxygen and ageing helps explain a curious observation made over a 100 years ago." "The observation that most animals have a fixed number of heart beats in their lifetime, around a billion." "A shrew lives life in the fast lane." "Its heart skips along at 500 beats a minute, using up all its heartbeats in less than four years." "By contrast, an elephant's heart pumps a leisurely 30 times a minute." "It can live up to 80 years." "And a tortoise, Iike Harriet, with a very low resting heart rate, just goes on and on." "The more you rush around, the more oxygen you need, and the more free radicals you product." "And more free radicals means more damage." "If free radicals are the main reason why we age, then perhaps we should be looking at ways to reduce the amount we produce." "michael Young is in training." "He's hoping that his training will allow him to live an exceptionally long and healthy life." "michael is nowhere near as fit or as strong as the men he's swimming with." "But he's convinced that despite outward appearances, it is he who will win the race of Iife." "michael is 42 years old, and determined to live at Ieast as long again." "His life plan is not based on exercise, but diet." "essentially, it's an attempt to grow older more slowly, really, and to minimise the dangers from all these degenerative diseases that are going to happen by the time most people are 60 or 70, they're going to start." "And I want them to start a little bit later in my Iife, and that's what I'm on this diet for." "michael has read extensively on the science of ageing, and for the past three years he's been putting theory in to practice." "He has begun a radical vegetarian based diet." "That's because fruit and vegetables are the best source of vitamins, Iike A, C and E." "These are so-caIIed antioxidants." "They help soak up free radicals." "But fruit and veg alone will not greatly extend life." "So michael also plans to reduce the amount of free radicals his body produces." "He's trying to do this by eating less, far, far less." "I find Fridays is a good day for actually eating not very much, because that's the day when I go to my war games club, and the excitement of the war games club, and playing with the model soldiers takes my mind off the fact" "that I'm actually quite hungry." "And so often I'II manage on just perhaps an apple on Fridays." "michael is, by profession, a military strategist, and when it comes to ageing, he has studied the odds." "He eats less than 1500 calories a day." "And this diet isn't a short term tactic, it's a lifelong campaign." "michael is right that a diet high in fruit and veg and Iow in fat will help him avoid mid life diseases." "But, will eating less help him live longer?" "It sounds unlikely, unless you know the dramatic tale of two mice." "For mice, everything is in fast forward." "From tot to teens in a few months, then old age and death at two." "But this isn't inevitable." "In what is now a classic experiment, researchers took two young mice." "Cne mouse was allowed to eat as much as she liked." "She lived a typical couch potato existence, and died soon after reaching two." "The other mouse led a spartan existence." "She got half the number of calories." "She lived on, bright and active, dying at the grand old age of three." "In human years, that over 120." "It must have been one of the really exciting moments in science, back in the 30s, when they suddenly realised that simply by changing how much food a mammal ate, they could change how long it lived." "I mean, it opened up all sorts of possibilities, both in terms of understanding ageing, and also, perhaps, being able to manipulate how long mammals would live." "Stay slim, stay young." "It undoubtedly works for rodents, but what about humans?" "After three years of dieting," "michael has come to a medical clinic to have his biological age assessed." "A reliable estimate of how well someone is ageing can be by measuring the thickness of the arteries in the neck." "So we're going to use an ultrasound transducer in order to give us a picture using soundwaves, and we're actually going to measure the lining of the artery, just to ensure that there is no thickening occurring there." "So it's this that we check very carefully, because if is -this has a major block.." "And in your case, yours is nice and thin." "When you said those words it made a tremendous difference to me, because it shows it's the first actual evidence" "I've had that perhaps my diet is doing something." "Can I have a picture of that?" "You can have a picture." "We'II make a nice picture for you." "The ultrasound measurements show" "michael's arteries are in very good shape." "They're those of a man ten years younger." "And he's also certainly managed to keep his weight down." "He's six foot tall, but only 58 kilos, about a 130Ibs." "The key thing that came out from the initial measurements that we made is that your height to weight ratio, your body mass index was very, very low." "So that really is quite underweight for your height." "although his diet seems to have kept his arteries young, it hasn't been good for his bones." "michael needs more calcium and more exercise." "The other scan we did was the bone mineral density scan, and bone mineral density scan shows that the bones are certainly weakened at both hip and spine." "It's weakened, but it's not osteoporotic yet." "Now that is quite an unusual finding in a 42 year old man, and I think that that's the key area for improvement, reducing your risk of having a fracture and improving your longevity." "Yes, okay, that -that seems right." "So I think I ought to start on weight bearing exercises." "Trying to stay slim is very hard, and no-one yet knows if radical diets" "like michael's really will extend human life." "And anyway, most people would prefer to eat lots," "live fast and live for a Iong time." "The encouraging thing is that there are animals that can dojust this." "ZooIogist, Stephen Austed, is off to capture some." "The animals he's after are mouse sized." "Yet the live at Ieast ten times as long, a full 30 years." "And they live life at full throttle." "They're bats." "What makes a bat so fast living is that, first of all, it takes a Iot of energy just to stay alive." "Its normal rate of energy use when it's resting is high." "Cn top of that, it flies." "flying is a very energetically expensive way to get around." "Cn top of that, it uses its voice to locate its prey, and so it's screaming all the time." "A bat is basically a mouse or a shrew with wings, except they expend even more energy than a mouse or a shrew, and yet they live many, many times longer, probably ten to 50 times longer than" "a mouse or a shrew would live in the wild." "How they do it is the great unanswered question." "If bats are burning up energy flying around, then they must be taking in a Iot of oxygen, so they must have evolved ways of limiting the damage caused by oxygen, and its by-products, free radicals." "Bats are not the only animals that live fast and defy the normal rules of ageing." "Most creatures that take to the wing live longer." "Some birds can live for more than 60 years." "So how do birds do it?" "The only way to find out is by studying them in the lab." "Domestic budgerigars live for over 18 years and are ideal candidates for research." "well, these birds are exceptionally long lives, so we're looking at in to their cells to ask how do they manage to resist oxygen as well as they do." "Steve Austed and his fellow researchers are about to try a simple experiment, exposing cells taken from different animals to pure oxygen." "The first group of cells have been taken from a mouse." "The mouse cells are destroyed by oxygen" "Then the researchers exposed budgerigar cells to the same level of oxygen." "The weight is tantalising." "The results are very different." "In contrast to mouse cells, oxygen has little effect on budgie cells." "well, what the budgerigars are doing on the cellular level is that they've developed an enormous capacity to withstand oxygen." "They do not have their cells damaged to the same extent, and their cells survive much, much better than mouse cells, or even human cells." "Steve Austed believes birds are able to resist oxygen attack because they have much better defences." "Their cells are packed with powerful antioxidants." "If he's right, then it's antioxidants that are likely to form the basis of any elixir of youth." "Cne place where new antioxidants are being tested is the Buck Institute in california." "It's a multi million dollar not for profit foundation, staffed by scientists from around the world." "Their goal is to try and understand how and why the body ages." "Doctor Simon MeIov is particularly interested in the way our natural defences cope with free radicals." "clearly we're not dying at the age of 20 from age related disease." "Now we had to evolve defences against those free radicals, or we wouldn't have survived." "The body does manufacture its own natural antioxidants." "These molecules float around inside each cell, neutraIising any free radicals they meet." "nonetheless, some free radicals elude capture." "well, we have defences against free radicals which are produced." "These defences are imperfect, but they exist, so obviously these defences are operating at a level sufficient to prevent many of the age related diseases and changes we see with ageing throughout the vast majority of our lives." "And at some point though, the balance is tipped." "Cver the years, the free radicals that escape overwhelm our defences and slowly and inevitably cause massive wear and tear to our cells." "And it is this accumulative wear and tear that most experts now say is the main cause of ageing." "So a true elixir of youth would be a drug that would help the body's defences in its war against free radicals." "At the Buck Institute, they may have developed just such a drug." "This brown powder is a synthetic catalytic scavenger, or SCS for short." "It may be the elixir of youth." "It's a powerful antioxidant." "At the Institute, they wanted to know if SCS would destroy free radicals in the cells of living animals." "Doctor MeIov decided to test it out on the nematode worm." "He invited worm expert," "Doctor Lithgow from Manchester, to assist in his research." "The particular nematode we study has real advantages for ageing." "It has a 20 day lifespan, really short, and that allows us to do lots of experiments." "And that 20 day lifespan encapsulates the whole of the complex biology we see in ourselves, so we have the whole of a life history in 20 days." "The test was simple." "Cne group of worms would get the drug, the other group would be left untreated." "It was then just a question of waiting and watching." "myself and my colleagues who were undertaking these experiments were coming in to the lab each day," "looking down a microscope at these animals, and we would have a well of treated animals alongside a well of untreated animals." "A young nematode worm is small and active." "As they age, they get bigger and slow down." "When they stop moving altogether, you know they're dead." "You could tell that the treated animals were doing a Iot better." "They were fertile, they were behaving as normal." "They just looked more youthful." "The worms on the Ieft were treated with the free radical scavenging drugs." "They stayed young and vigorous." "while the untreated worms on the right grew older and much slower." "And, you know, the worm's eye view, you can just imagine these guys looking through the plastic wall at the chaps in the next well dying because they hadn't been treated with the drug." "It's a really dramatic effect." "The treated worms lived way beyond their normal 20 days." "Some more than doubled their lifespans." "normally, we're used to very small changes in lifespan when we're trying to deal with a compound, and suddenly here was something that was having a very dramatic and large effect on the lifespan of the animal," "and that was quite unheard of." "This was the first time anyone had shown that a drug could dramatically increase the lifespan of an animal." "Looking at the increase of the survival of the nematodes, and I rememberjust being astonished, and just being literally blow away by the implications of this." "Here it was that we had a drug that we had demonstrated that it extended the lifespan of a multi cellular organism." "The implications were that it wouId do the same thing in mammals, and we're currently very interested in evaluating that." "They are now trying the drug on mice, and early signs are that it is having an effect." "Further down the line, they hope to test this drug, or one like it, on humans." "But do we really want to live longer?" "Cne fear is that radically increasing lifespan will lead to over population." "Yet history suggests otherwise." "In most wealthy countries, birth rates are actually falling, even though life expectancy has nearly doubled in the Iast 100 years." "But it's notjust prolonging life that interests MeIov, it's the idea that in the future we could stay young longer." "Everyone is just starting to understand how the world works, and all of a sudden your body starts falling you." "And so how much better would it be if that weren't to happen, and you could use the accumulated wisdom throughout your lifetime to good effect, instead of having your faculties fall." "It's very unlikely there will be a single solution to the problem of ageing." "Better drug treatments, replacing failing organs, even manipulating genes may all play a part." "These technologies are in their infancy, but technology has a way of exceeding expectations." "Imagine what's going to come next, and the only thing that I'm willing to say is that it's going to surprise us that the things we think are impossible today are not going to be impossible in the future," "which is why I know that by the end of the 21st Century we're going to be able to completely manipulate what it means to be a human being." "The new science of genetics promises to change our world beyond all recognition." "Whether it's for better or for worse will not be decided by science, but by society." "Knowing how to build a human may ultimately be less important than what we do with that knowledge."