Is it time for the Grim Reaper to pick up his P45?

So scientists have discovered an elixir of life - a `longevity gene' to slow down, even halt, the ageing process. Well, sadly not, writes Steve Connor
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The Independent Online
Death is the one certainty in life, although its timing is frequently unpredictable. Methuselah was supposed to have done it when he was 969 years old. Most of us can expect to do it after a more modest three score and ten. For the lucky few, such as Jeanne Louise Calment, the French woman who celebrated her 120th birthday earlier this year, death might not come until well past the hundred mark.

Ms Calment is old enough to have known Vincent Van Gogh, who she remembers as a loathsome boozer she met in her father's shop in Arles. If she survives the next few months she will become the oldest person ever, overtaking Shigechiuyo Izumi, a Japanese farmer who died in 1986 at the age of 120 years and 237 days. The two share little in common except perhaps a fondness for a regular but modest drink. Ms Calment likes a glass of port, Shigechiuyo's preference was shochu, a powerful white rum. "I would rather die than give up drinking," he once said before he did both.

To live well beyond one's first century is a rare achievement, but more of us are dying older. Life expectancy has improved dramatically over the past 200 years, and it is not all due to lower child mortality. In developed countries, men and women are living longer than they have ever done in history. Between the Bronze Age and the start of the Industrial Revolution life expectancy increased little, from a mere 30 years to 40 years. Over the past 150 years, however, the average lifespan has doubled to about 78 years, with women living slightly longer than men.

Now there is fevered speculation about the implications of scientists discovering a ``gene for longevity'' that could supposedly hold the key to prolonging human life by 40 years, as well as delaying the onset of age-related diseases, from arthritis to senile dementia. Even though the genetic trait has so far only been found in an obscure microscopic worm, this has not stopped some from suggesting that soon we may all live to be healthy, active Jeanne Louise Calments.

But can science cheat death? Although more people are becoming centenarians, primarily because of improvements in health, housing and diet, few if any of us will be able to surpass, let alone equal, the lifespan of Ms Calment. The maximum limit to human life seems stubbornly set at about 120 years. If social and medical advances can improve life expectancy, why can't they push the limits of human longevity nearer to Methuselah's epic (if unconfirmed) achievement? In fact, why can't we live forever?

It all comes down to that other great certainty of life. We grow old. From early adulthood, we begin to deteriorate. At 25 years, our hearts, lungs, muscles and kidneys are at their peak. By 45, they are starting to fade, matched by a rise in cholesterol levels. At 65, maximum heart rate falls to 87 per cent of what it was, lung capacity by 62 per cent. The decline continues into old age with a rise in disorders of later life - cancer, strokes, heart disease and Alzheimer's. The Grim Reaper is never far behind.

Scientists have amassed considerable evidence that genes play the crucial role in deciding the maximum limits to human lifespan. Even if we can avoid all the nasties ready to nobble us on the journey of life, it is our genes that ultimately decide our fate.

Tom Kirkwood, professor of gerontology at Manchester University, has come closest to formulating the definitive theory of ageing, which looks at death from the dispassionate vantage point of our genes.

This view sees our mortal bodies as mere vehicles for conveying our genes to the next generation. But like all complex structures, our bodies are expensive to maintain and repair. We need to expend so much energy on mending things which go wrong that there comes a time when it is no longer cost-effective - or even possible - to carry on. For our genes - our biological raison d'etre - this is fine, providing they are firmly ensconced in the bodies of our offspring, who are being readied for genetic reproduction.

Professor Kirkwood calls this the "disposable soma theory" (soma meaning body), and there are close parallels with the idea of artificial obsolescence. Just as Henry Ford went to great lengths to try to build a Model-T car that did not last forever, so the body has to balance the costs of continual repair against the benefits of a long life.

Anyone accustomed to observing nature will have noticed it is rare to see an animal that is noticeably old. Ageing is a feature peculiar to humans. Professor Kirkwood explains that this is because our systems of body maintenance evolved at a time in human prehistory when life expectancy was much shorter and before the social and medical advances of recent times greatly reduced our early mortality. "At the life stage when most species have died off, we are beginning to experience the effects of ageing."

Scientists can demonstrate the importance of genes in deciding when death strikes by allowing laboratory animals to grow old before they are allowed to reproduce. Fruit flies that are kept until the age of 70 days - astonishingly old by their standards - before breeding will, over successive generations, result in a strain of fly that lives up to 40 per cent longer than ordinary flies. This shows the importance of selecting certain genes in improving longevity, but the drawbacks included a fly that was less fecund than its short-lived cousin. In evolutionary terms it was a non-starter.

Recent interest in ageing research has focused on a tiny nematode worm called Caenorhabditis elegans, following the discovery some years ago of a mutation in a gene called AGE-1 that slows down the ageing process. The mutation appears to cause the increase in production of enzymes in the worm that mop up oxygen-rich substances which are highly damaging to living material, particularly the genetic blueprint, DNA.

Some of the more flamboyant press coverage of the finding has suggested that the research raises the hope of discovering the elixir of life - a gene for longevity that could prolong human life by 40 years and delay the onset of cancer and other age-related disorders. The reality, as always, is a little less exciting and far more complex.

Caenorhabditis elegans has a precise number of cells to its body - 959 in all - and is exceedingly simple compared with the human body. It is this simplicity that has drawn scientists to studying it, hoping it will shed light on the highly complex ageing process in humans. Despite its usefulness as a laboratory model of ageing, however, Professor Kirkwood believes it is an "enormous extrapolation" to put the worm research into the context of prolonging human life.

``Ultimately, the understanding of human longevity is an extraordinarily complex undertaking," he says. "We believe there is effectively a biological upper limit for human beings which cannot be altered. We are interested in increasing the quality of life rather than increasing lifespan.''

The worm research confirms the importance of mopping up highly reactive chemicals, such as oxygen-rich molecules and "free radicals", so preventing them building up and damaging the tissues. Respiration is essential for life, but it produces many of the chemical by-products that cause ageing. Those organisms that respire slowly, such as alligators and Galapagos tortoises, often live to a ripe old age; others in the respiratory fast lane, like hummingbirds, shrews (and some rock stars), die before they get old.

This all fits neatly into Professor Kirkwood's disposable soma theory. Life is a slow accumulation of errors that result in catastrophic failure because the body is not designed by its genes to keep up with the continual onslaught. Scientists such as Professor Kirkwood believe it may be possible to slow the ageing process down, not by swallowing any elixir or injecting genes, but by eating healthily, taking exercise and keeping mentally active.

The search for the genetic components that give people such as Ms Calment a long life has already begun, in a study of centenarians in Paris and, soon, in Manchester. It is well known that longevity runs in some families, a sign that genes are involved, and the hope is to identify those inherited traits.

For John Grimley Evans, professor of clinical geratology at Oxford University, the real issue is not how to extend the maximum human lifespan, but how to cope with an increasing number of older people. ``More and more people are running into their biological buffers. Genes may give us a certain life expectancy, but the environment eventually gets us,'' he says. The big question is whether living longer means being more disabled in later life, he says.

What is known is that the older you are, the more likely you are to die quickly when you get ill. "The first imperative for those wishing to be a healthy hundred, therefore, is to be informed, to stay in command, and to be thoroughly obstreperous in refusing to be fobbed off with second- rate medical care," Professor Grimley Evans says.

As for dreams of an elixir of life, he gives it a definite no. ``Even if we didn't die of natural causes, we'd fall under a bus or die of some other accident.'' The trouble, it seems, is that death comes in so many guises.

The facts of life and death

Life expectancy has risen dramatically over the past 150 years, primarily because of improvements in living conditions and advances in medical science, notably the introduction of vaccines. The average lifespan in the mid 19th century was 42 years. In the UK today it is 72 for men and 78 for women.

Improvements in life expectancy are true for every age group. If they continued without limit, with mortality rates falling by 1 or 2 per cent a year, it would not be unusual for people to reach the age of 125 by the middle of the next century. Some would even reach 140 before dying.

There is, however, a biological limit on longevity that stops this from happening. As people grow older, the number of further years they are likely to live - their life expectancy - inevitably falls as well. Although life expectancies of people who lived in the last century were lower, the difference between then and now becomes smaller in older people.

For instance, in 1850, a baby boy had a life expectancy of about 40 years, but this was largely due to the enormous childhood mortality at the time. This compares with a life expectancy of over 70 for boys born today. A 20-year-old man living 150 years ago could expect to live about 40 more years. Today, he can expect to live up to 55 more years.

This differential begins to whittle away with age. Only a few years separates the life expectancies of 60-year-old men then and now, and by the time people reach 100, it is almost the same.

Because men living 150 years ago were exposed to very different living conditions and health environments than men alive today, the existence of a limit to life expectancy is a sign that maximum longevity is under the control of our genes - which are the same genes that existed 150 years ago.

According to Emily Grundy, a Medical Research Council demographer at King's College London, the best estimates suggest that about 60 per cent of boys and 70 per cent of girls born in 1981 will survive to celebrate their 75th birthday in 2056. ``Of the girls born a century earlier in 1881, over 40 per cent died before the age of 55, many in infancy, only a third reached 75.'' Only half the boys reached the age of 55 and a mere 20 per cent survived to 75.

At the turn of the century there were fewer than half a million people - about 1.5 per cent of the population - aged 75 and over. In 1991, this proportion had risen to more than 9 per cent, or 3.5 million people. Although this increase is largely due to historic falls in birth rates, it is also due to more people living longer, Dr Grundy says. ``Now that Britain has had low birth and death rates for some time, changes in death rates at older ages are having a stronger effect on age composition."