Slowing the clock

Some of our cells are immortal and some die with us. Tom Wilkie reports on how understanding the difference may help us slow down ageing
April 19, 1999

In Petronius's satyricon, old age is portrayed as a terrible thing. Deiphobe, the Sibyl of Cumae, hangs from the roof of her cave, withered, ancient and shrunken. Apollo has granted her wish to live for as many years as she holds grains of sand in her hand. But when asked what she now most desired in the world, she replies: "I desire only death." She had asked for eternal life, not eternal youth.

Now, more than 2,000 years later, modern science may be opening the way to refuting the wisdom of the classical writers. According to Tom Kirkwood, human ageing is neither necessary nor inevitable. He should know. He is Britain's first professor of biological gerontology (at Manchester University) and the main author of the most influential model of ageing in modern science: the "disposable soma" theory.

Kirkwood does not promise practical applications yet-he is not peddling elixirs of youth. But he holds out the prospect that, with increased understanding of why we age naturally, it may be possible to intervene to slow or even to stop human ageing.

In a sense, the process has already begun. In the week that his book was published, the annual British Social Trends reported that life expectancy is now 75 for men and 80 for women, much longer than the Biblical limit of three score years and ten. Much longer, too, than in Germany a century ago, when Bismark set the pension age at 65 on the understanding that average male life expectancy was then just 66.

The process is global. Around the world, people are living longer. There has also been a widespread decline in infant mortality. The two processes combined means that by 2050, more than one in five of the world's population will be aged over 65.

But is this just the result of modern medicine removing other causes of death which used to carry us off prematurely? And, if so, will our extended life span leave us wishing we were dead, like the Sibyl? The same Social Trends reports that in the age group 65-74, 52 per cent of men and 51 per cent of women say that they suffer regular pain.

But for Kirkwood, the "wear and tear" theory of ageing is fallacious. Human beings are not like motor cars or other artefacts of our modern world. We are made up of living cells which can repair and renew themselves indefinitely. Bacteria do so on a microscopic level, and some larger animals, such as the sea hydra, are truly immortal (barring accidents).

Some of the cells in our bodies are also immortal: the egg cells belong to a lineage which stretches back billions of years, to the very beginning of life itself, and this lineage has not been broken by wear and tear. But it is only these egg cells-the germ line-which have a future and which will survive into the future. All the other cells in our bodies-the somatic cells-will die with us. The puzzle is why somatic cells die when germline cells-the eggs-are immortal.

The answer for Kirkwood is to be found in evolutionary theory. Animals in the wild do not, usually, die of old age. Predation, not degeneration, carries off most of them. For those few who are at the top of their respective food chains and do not have to fear predators, accident, starvation and disease are the normal causes of death.

And what if we avoid the latter? Our cells depend upon oxygen to function, but oxygen is a notoriously reactive chemical capable of forming what are known as "free radicals." These cut huge swathes of damage through the orderly society within a body cell. The damage can be repaired, but it costs energy to do so. And what is the point of investing huge amounts of energy in repairing and maintaining body cells, if the only result is that a predator gets a better meal?

By a process of trial and error, evolution reaches a trade-off. It invests hugely in germline cells, because some of them at least will get through to following generations. But it invests only enough in the somatic cells to get them through reproduction to roughly the point at which the animal would die anyway, as a result of predation or other natural causes.

How long we live, then, is regulated not by genes designed to cut us off for the good of the species, but rather by the limits of genes designed to keep us alive. Just as wrong as the wear and tear theory is the terminator gene: the idea that we are programmed to die so that we do not hang around using up scarce resources which younger and fitter individuals could use better. Such a gene would disappear from the population, because it confers no advantage on its possessor.

Now that humanity is no longer dying of natural causes in the wild, we are, according to Kirkwood, bumping up against the limits of the disposable soma design of humans. But his point is that the limits can be shifted. Increase the amount of energy spent on repair and maintenance, and we should age more slowly.

As yet, there is no "magic bullet," no pill we can pop, only a moderate diet; healthy exercise; perhaps a touch more vitamins E and C (for their antioxidant benefits); and hormone therapy for post-menopausal women. But ageing need not mean pain and discomfort. The Social Trends finding may be peculiar to post-Thatcherite Britain. Studies in the US show an improvement in the health and sense of well-being of older people.

More people are living longer and better lives than ever before. But politicians and economists describe what is surely a triumph of the late 20th century, in the gloomy terms of "the demographic timebomb." Science seems to be out of step with the economy. Science is creating more older people just as the public and the private sectors are switching to a younger (and cheaper) workforce and encouraging workers to retire even earlier than the state pension age of 65. But this imbalance can be cured at a stroke of the pen. If, in the future, men live healthy lives until they are 75 and women until they are 80, then the pension age should be raised to 70 and 75 respectively.
Time of our lives

Tom Kirkwood

Weidenfeld and Nicolson 1999, ?20