Is science on the brink of creating the elixir of life?
By MICHAEL HANLON Last updated at 5:00 AM on 9th October 2010
Once I had a very odd dinner with an elderly and distinguished scientist who told me how he planned to live for ever - or at least for a very long time indeed. We ate in his beautiful house by the sea in California. Our meal consisted of one bowl of rice each and a glass of water. With this extreme diet, my host said - limiting himself to 800-1,000 calories a day (the average male is recommended to consume 2,500) - he hoped to stave off death for many more decades.
Such a regime was based on the well-established theory that by reducing calorie intake, people can dramatically increase their lifespans. This had been shown, after numerous scientific investigations, to work in animals from fruit flies to mice. Professor Roy Walford, a biologist at UCLA, was 74 years of age when I met him. He had no doubt that extreme calorie restriction would work in people, too. However, despite his punishing diet, he was to die five years later from the auto-immune disorder Lou Gehrig’s disease. Seventy-nine years was a little better than the three score years and ten which have been approximated as the human lot since Biblical times - but his innings only matched the average lifespan for an educated, middle-class white California male of his generation. It is tempting, then, in the light of this story, to write off the theory that by eating the bare minimum we can slow the ageing process. But it seems Professor Walford was probably on to something, even if the fates conspired to ensure that he personally did not benefit from his diet thesis.
For there is a growing scientific consensus that ageing - against which humanity has been battling for millennia - might not be inevitable.
Of course, the quest for eternal youth has been led by charlatans, frauds and snake-oil salesmen through the ages. There is money to be made by promising the Holy Grail - as the questionable claims on the labels of countless anti-ageing beauty products will attest. For centuries, lotions and potions have been touted as elixirs of longevity. These have ranged from products containing monkey glands to injections of minced dog testicles. Unsurprisingly, all have failed. Still, the search continues.
We have been told that exercise, red wine, chocolate, Vitamin C and various cocktails of antioxidants are the answers. The latest elixir claim comes from scientists in Italy, who announced this week that mice given dietary supplements rich in three amino acids (similar to the concoctions favoured by human bodybuilders) lived on average 12 per cent longer than mice fed on ordinary food (see: ScienceLongLife). For humans, this would mean about an extra ten years of life. And yet the world still awaits its first 125-year-old. The record stands at 122 years - achieved by Frenchwoman Jeanne Calment, who died in 1997. But the truth is, charlatans apart, the ageing process may be more amenable to change than was thought.
For a start, life expectancy (the number of years a newborn is predicted to live) is increasing by five hours a day in Britain. This means a baby born in five years’ time should live a year longer than a baby born today. This is, for the most part, simply a result of better healthcare. For evidence we need only look at the first big jump in life expectancy, which took place in the 19th century when infant mortality rates dropped because of improved diets, better medicine and proper sanitation. We haven’t conquered age, it’s just that more and more of us are living to our full potential. But we may now be nearing a surprising breakthrough.
Until recently, those scientists working on increasing the longevity of fruit flies or mice have shied away from making claims that humans could benefit from their work on genetics. But now, as Stipp points out, this attitude seems to be changing; more and more experts now say that human lifespan can be increased - and what’s more, they agree that it would be a good idea.
How we grew old, and why, was a mystery until recently. It was commonly supposed that our bodies simply wore out, like machines. But this wasn’t a good analogy. Unlike most machines, our bodies are equipped with efficient repair systems that keep our cells healthy for decades. In fact, we do not really start to ‘age’ at all until we are into our 20s. So, discovering why these mechanisms stop working as we enter middle and old-age is the key to understanding the ageing process. Ageing is, after all, not entirely inevitable. Several organisms appear to hardly age at all and live for centuries.
Humans are among the longest-lived of all species, but our longevity is exceeded by some giant tortoises which can live for nearly 200 years. Bowhead whales have recently been found, alive and well, with antique harpoons embedded in their skulls which can be dated back to the 1790s. Some of these animals may be more than 300 years old. There is a pattern in all this. Big creatures tend to live longer than small ones. Anything that can fly or swim tends to live longer than animals stuck on the ground. Understanding these differences gives us our first clue as to how ageing works - and to what might be done to delay it.
The evolutionary theory of ageing states that animals age at a rate commensurate to their likely survival time in the wild. Mice age quickly because - being small and feeble - they are likely to be eaten, starve or perish due to cold before too long. Evolution has given the mouse a body that literally lives fast and dies young. It’s full of sex hormones turbocharging its chances of reproducing before it is eaten by predators. It makes little sense for a mouse to be equipped with, say, anti-cancer mechanisms, if the chances are that it will be an owl or cat’s dinner within a year or two.
On the other hand, elephants age slowly because, being big, they are hard to kill. It takes a long time for them to die of starvation and they cope well when times get tough. So elephant bodies have evolved complex DNA repair systems which can keep them going for half a century or more.
Birds also live a long time because, although small, they can fly and thus avoid predators. Bats live longer than mice for the same reason, and porcupines and tortoises are long-lived simply because they make a difficult meal. In each case, their bodies age slowly to make the most of their potential life spans. Still, knowing why we age tells us little about how we age - and even less about what we might be able to do about it. There is growing evidence, however, that the very hormones that enable us to reproduce - those which produce eggs and sperm - may in themselves contribute to the ageing process. ‘Death,’ said one biologist, ‘is the price we pay for sex.’
Advances in DNA analysis - reading the entire genetic codes of organisms - have opened up exciting new areas in ageing research, allowing scientists to pinpoint individual genes which may be be responsible for the breakdown in our bodies over time. Yet the reality is that many of the resulting ‘breakthroughs’ have proved to be dead ends. For decades, ‘free radicals’ (waste chemicals produced by our bodies as by-products of respiration, digestion and the action of muscles) have been suggested as possible drivers of the ageing process.
Big creatures tend to live longer than small ones. Anything that can fly or swim tends to live longer than animals on the ground.
Some scientists have claimed that we should take large quantities of free-radical neutralisers called antioxidants (which include Vitamin C and are best found in fruit and vegetables). Yet Vitamin C, it turns out, may actually increase free-radical damage and very large doses can interfere with the body’s natural repair mechanisms.
It is such contradictions that have led researchers to focus, instead, on calorific restriction. Mice placed on near-starvation diets have seen their life expectancies increase 20-35 per cent. If such results were achievable in humans, the average Briton’s life expectancy would rise to almost 100 - with the potential to carry on to 150. This is precisely what Professor Roy Walford was trying to achieve with his grimly tedious rice and water diet in California. And the truth is that research into whether calorie restriction will greatly extend our lifespans would take decades to reach firm conclusions - simply because we are so much larger than mice.
Even so, research on rodents has uncovered how extreme calorie restriction appears to switch on a genetic mechanism called a stress response. This has evolved to allow animals to survive tough conditions (such as a very hard winter when little food is available). It seems the bodies of mice - and possibly those of humans, too - react to starvation by boosting their repair mechanisms, triggering anti-inflammatory responses which slow the damage done to vital organs as they age.
The problem for humans is that near-starvation is unlikely to catch on. What people are much more likely to turn to are drugs which mimic the effects of extreme calorie restriction, without having to live on lettuce. And such drugs may soon be available. One could be based on the chemical resveratrol which is a plant compound found in red wine. In 2006, Harvard scientist David Sinclair found that this could activate a stress-response gene called Sir2 in mice which extended their lives.
Vast fortunes are being spent by the big drug firms on anti-ageing drugs
The happy fact that the elixir of youth is found in wine was suggested as the possible reason why the French, who eat a lot of supposedly unhealthy meat and cheese, smoke too much and drink a lot of alcohol, have one of the world’s highest life expectancies.
Then, last year, three teams of researchers in the U.S. reported that another chemical which mimics the effects of starvation, called rapamycin, makes mice live longer by suppressing the onset of cancer. The chemical was isolated from a fungus found on Easter Island in the Pacific. Unsurprisingly, the big drug firms are trying to exploit these discoveries. Vast fortunes are being spent on anti-ageing drugs which mimic calorie restriction. The problem, sceptics point out, is that the ageing mechanism in rodents may be quite different to the one in humans.
Therefore, resveratrol and similar chemicals may not prove to be the answer (the same may be true of the Mr Universe protein supplements trumpeted this week). But the likelihood is that, in a few years, pills will be developed that will be able chemically to copy the effects of a near-starvation diet and that may well increase lifespan in humans.
If this happens, what would a world of 130-year-olds be like? Of course, there is a big difference between being a healthy 130-year-old and someone who has spent the last 40 years of their life suffering from dementia. So what about the anti-ageing pioneer Roy Walford? Ironically, his death was caused by a rare disease that is exacerbated, not ameliorated, by a low-calorie diet. But if he was right, then by helping publicise what was once an obscure field of scientific research, his last, hungry years by the Pacific may not have been in vain.
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