Tue, 26 Oct 2010 09:37 UTC
It's an extraordinary claim. But scientists say you can extend your life and stay fit throughout old age - just by a change of diet that switches on your youth gene...
For centuries man has dreamed of being immortal, fixated on tales of magic fountains that restore youth, the rejuvenating power of a vampire's bite or asses' milk.
More recently came claims that injections of monkey glands or hormone supplements would make us live longer.
But so far, what's actually worked are medical advances such as vaccines and better living conditions. Over the past century these have boosted average life expectancy by far more than 50 per cent, from 50 to 88.
The problem is that this longevity does not mean a healthier life. Indeed, thanks to chronic diseases such as diabetes and arthritis, we're becoming like the Struldbruggs - the miserable characters in Gulliver's Travels who were immortal, but still suffered from all the diseases of old age.
Gradually they lost their teeth, their hair, their sense of smell and taste. All their diseases got worse and their memory faded, so they had no idea who their friends and relations were. At funerals they wept because they couldn't die.
But now a U.S. geneticist is thought to have discovered the secret to a long life, full of health and energy. And the answer might be as simple as cutting down on carbohydrates.
Professor Cynthia Kenyon, whom many experts believe should win the Nobel Prize for her research into ageing, has discovered that the carbohydrates we eat - from bananas and potatoes to bread, pasta, biscuits and cakes - directly affect two key genes that govern youthfulness and longevity.
She made her remarkable breakthrough after studying roundworms, specifically the C.elegans, a worm just a millimetre in size that lives in soil in temperate climates all over the world.
By tweaking some of their genes she has been able to help these worms live up to six times longer than normal. 'Not only that, but we also know how to make them stay healthy all that time as well,' she told an audience at the Wellcome Collection in London earlier this month.
So, what do worms have to do with us?
A great deal, it seems. Professor Kenyon's work has been successfully repeated in labs around the world - the genes she found controlling ageing in worms do the same thing in rats and mice, probably monkeys, and there are signs they are active in humans, too.
This work has revolutionised our understanding of ageing, explains Jeff Holly, professor of clinical sciences at Bristol University.
'Ten years ago we thought ageing was probably the result of a slow decay, a sort of rusting,' he says. 'But Professor Kenyon has shown that it's not about wear and tear, but instead it is controlled by genes. That opens the possibility of slowing it down with drugs.'
So how does a worm hold the key to human ageing?
At 18 days old the average roundworm is flabby, sluggish and wrinkled. Two days later it will probably be dead.
However, Professor Kenyon, based at the University of California, San Francisco, found that damping down the activity of just one of their genes had a dramatic effect.
'Instead of dying at about 20 days, our first set of mutant worms carried on living to more than 40 days,' she says.
'And they weren't sluggish and worn out - they behaved like youngsters. It was a real shock. In human terms it was the equivalent of talking to someone you thought was about 30 and finding they were actually 60.'
With more sophisticated genetic manipulation, she now has some worms that have lived for an astonishing 144 days. An increase of that proportion would allow humans to live to 450.
Scientists already knew how to make laboratory animals live longer and healthier lives - you just cut back their calories to about three-quarters of their normal amount.
It's not a practical solution for humans, because you feel cold and hungry all the time.
But what Professor Kenyon found out was why drastically reducing calories has such a remarkable effect.
She discovered that it changed the way two crucial genes behaved. It turned down the gene that controls insulin, which in turn switched on another gene, which acted like an elixir of life.
'We jokingly called the first gene the Grim Reaper because when it's switched on, the lifespan is fairly short,' she explains.
The second 'elixir' gene seems to bring all the anti-ageing benefits - its proper name is DAF 16, but it was quickly nicknamed 'Sweet Sixteen' because it turned the worms into teenagers.
'It sends out instructions to a whole range of repair and renovation genes,' says Professor Kenyon.
'Your supply of natural antioxidants goes up, damping down damaging free radicals.'
These are the compounds produced by our body and the environment, which are linked to a host of diseases from cancer to Alzheimer's.
The Sweet Sixteen gene also 'boosts compounds that make sure the skin and muscle-building proteins are working properly, the immune system becomes more active to fight infection and genes that are active in cancer get turned off,' she adds.
Kenyon had stumbled on the genetic equivalent of Shangri-La, the fictional valley where people could live for years without really ageing.
Discovering the Grim Reaper gene has prompted the professor to dramatically alter her own diet, cutting right back on carbohydrates. That's because carbs make your body produce more insulin (to mop up the extra blood sugar carbs produce); and more insulin means a more active Grim Reaper.
So the vital second gene, the 'elixir' one, won't get turned on. To test this, last year she added a tiny amount of sugary glucose to the normal diet of some of her worms that had had their genes engineered so they were living much longer, healthier lives.
'The effect was remarkable,' she says. 'The sugary glucose blocked the "youthful" genes and they lost most of the health gains.'
But was this just a special feature of the roundworm or did we all have it?
Following Kenyon's lead, other researchers started looking for the Grim Reaper/ Sweet Sixteen combination in other animals - and of course in humans. They found it.
One clue came from a small remote community of dwarves living in northern Ecuador who are cancer-free. They are missing the part of the Grim Reaper gene that controls a hormone called insulin-like growth factor. The downside is they only grow to 4ft tall because the hormone is needed for growth.
But this missing bit of the Grim Reaper gene also means they don't develop cancer and are less likely to suffer from heart disease or obesity.
Professor Jeff Holly, who specialises in insulin-like growth factor, confirms that it is linked to cancer of the prostate, breast and colon.
In fact raised insulin levels, triggered by high carbohydrate consumption, could be what connects many of our big killers.
Research is at its early stage, but raised insulin triggers an increase in cholesterol production in the liver, makes the walls of blood vessels contract so blood pressure goes up and stimulates the release of fats called triglycerides (linked to heart disease).
Professor Kenyon's work is creating a wave of excitement among drug companies who've been researching molecules that will damp down the Grim Reaper and boost Sweet Sixteen, giving us the benefits of very low-calorie diets without the penalties. So far, none is very near being approved.
One way to reduce insulin levels is to exercise, which makes you more sensitive to it, which in turn means you need less of it. It also gives another health benefit in a surprising way. Exercise actually increases the level of damaging free radicals which stimulates the body to produce more protective anti-oxidants.
So should we all be trying to cut back on carbs to reduce our insulin levels?
It is a suggestion that flies in the face of 30 years of health advice to have a lower fat intake and eat plenty of long-lasting complex carbohydrates to keep the body supplied with energy.
There is no denying the extraordinary breakthrough Kenyon's work represents and she 'deserves the Nobel Prize for her findings about ageing', says David Gems, deputy director of the Institute for Healthy Ageing at University College, London.
However he isn't convinced we know enough for us all to start eating a low-carb diet.
'The exact role of insulin in health and ageing is a promising and fascinating area,' he says. 'But I'm not sure the evidence for the benefit of cutting carbohydrates and keeping insulin levels down is strong enough yet.'
But Professor Kenyon herself doesn't need convincing.
'Carbohydrates, and especially refined ones like sugar, make you produce lots of extra insulin. I've been keeping my intake really low ever since I discovered this.
'I've cut out all starch such as potatoes, noodles, rice, bread and pasta. Instead I have salads, but no sweet dressing, lots of olive oil and nuts, tons of green vegetables along with cheese, chicken and eggs.
'I'll have a hamburger without a bun and fish without batter or chips. I eat some fruit every day, but not too much and almost no processed food. I stay away from sweets, except 80 per cent chocolate.'
She is adamant it will be well worthwhile. 'You could have two completely different careers if you could stay healthy to 90,' she says. 'How fascinating that would be.'