exposed for the first time to selection for better health after two years of age - their bodies would deteriorate less rapidly. They would age more slowly. This proved an accurate prediction. On Sapelo, Austad found, the opossums not only lived much longer, but aged more slowly. They were healthy enough to breed successfully in their second year - rare on the mainland — and their tendons showed less stiffness than those in mainland opossums.8
The evolutionary theory of ageing explains all the cross-species trends in a satisfying way. It explains why slow-ageing species tend to be large (elephants), or well protected (tortoises, porcupines), or relatively free from natural predators (bats, seabirds). In each case, because the death rate from accidents or predation is low, so the selective pressure is high for versions of genes that prolong health into later life.
Human beings, of course, have for several million years been large, well protected by weaponry (even chimps can chase leopards off with sticks) and have few natural predators. So we age slowly -
and perhaps more slowly as the eras pass. Our infant mortality rate in a state of nature - of perhaps fifty per cent before the age of five — would be shockingly high by modern, western standards, but is actually low by the standards of other animals. Our Stone-Age ancestors began breeding at about twenty, continued until about thirty- five and looked after their children for about twenty years, so by about fifty-five they could die without damaging their reproductive success. Little wonder that at some time between fifty-five and seventy-five most of us gradually start to go grey, stiff, weak, creaky and deaf. All our systems begin to break down at once, as in the old story of the Detroit car maker who employed somebody to go around breakers' yards finding out which parts of cars did not break down, so that those bits could in future be made to a lower specification.
Natural selection has designed all parts of our bodies to last just long enough to see our children into independence, no more.
Natural selection has built our telomeres of such a length that I M M O R T A L I T Y 2 0 3
they can survive at most seventy-five to ninety years of wear, tear and repair. It is not yet known for certain, but it seems likely that natural selection may have given fulmars and tortoises somewhat longer telomeres, and Virginia opossums much shorter ones. Perhaps even the individual differences in longevity between one human being and another also indicate differences in telomere length. Certainly, there is great variety in telomere length between different people, from about 7,000 D N A 'letters' to about 10,000 per chromosome end. And telomere length is strongly inherited, as is longevity. People from long-lived families, in which members regularly reach ninety, may have longer telomeres, that take longer to fray, than the rest of us. Jeanne Calment, the French woman from Arles who in February 1995 became the first human being with a birth certificate to celebrate her 120th birthday, may have had many more repeats of the message T T A G G G . She eventually died at 122. Her brother lived to ninety-seven.9
In practice, though, it is more likely that Mme Calment could thank other genes for her longevity. Long telomeres are no good if the body decays rapidly; the telomeres will soon be shortened by the need for cell division to repair damaged tissues. In Werner's syndrome, an inherited misfortune characterised by premature and early ageing, the telomeres do indeed get shorter much more rapidly than in other people, but they start out the same size. The reason they get shorter is probably that the body lacks the capability to repair properly the corrosive damage done by so-called free radicals
- atoms with unpaired electrons created by oxygen reactions in the body. Free oxygen is dangerous stuff, as any rusty piece of iron can testify. Our bodies, too, are continually 'rusting' from the effects of oxygen. Most of the mutations that cause 'longevity', at least in flies and worms, turn out to be in genes that inhibit the production of free radicals - i.e., they prevent the damage being done in the first place, rather than prolong the replicating life of cells that repair the damage. One gene, in nematode worms, has enabled scientists to breed a strain that lives to such an exceptional age that they would be 350 years old if they were human beings. In fruit flies, Michael 2 0 4 G E N O M E
Rose has been selecting for longevity for twenty-two years: that is, in each generation he breeds from the flies that live the longest. His
'Methuselah' flies now live for 120 days, or twice as long as wild fruit flies, and start breeding at an age when wild fruit flies usually die. They show no sign of reaching a limit. A study of French centenarians quickly turned up three different versions of a gene on chromosome 6 that seemed to characterise long-lived people.
Intriguingly, one of them was common in long-lived men and another was common in long-lived women.10
Ageing is turning out to be one of those things that is under the control of many genes. One expert estimates that there are 7,000
age-influencing genes in the human genome, or ten per cent of the total. This makes it absurd to speak of any gene as 'an ageing gene'
let alone
It is no accident that the immortal cell lines used by scientists in the laboratory are derived from cancer patients. The most famous of them, the HeLa cell line, originated in the cervical tumour of a patient named Henrietta Lacks, a black woman who died in Balti-more in 1951. Her cancer cells are so wildly proliferative when cultured in the laboratory that they often invade other laboratory samples and take over the Petri dish. They even somehow reached Russia in 1972 where they fooled scientists into thinking they had found new cancer viruses. HeLa cells were used for developing polio vaccines and have gone into space. Worldwide, they now weigh more than 400 times Henrietta's own body weight. They are spectacularly immortal. Yet nobody, at any time, thought to ask Henrietta Lacks's permission or that of her family - who were hurt when they learnt of her cellular immortality. In belated recognition of a 'scientific heroine', the city of Atlanta now recognises 11 October as Henrietta Lacks Day.
I M M O R T A L I T Y 2 0 5
HeLa cells plainly have excellent telomerase. If antisense R N A is added to HeLa cells - that is, R N A containing the exact opposite message to the R N A message in telomerase, so that it will stick to the telomerase R N A - then the effect is to block the telomerase and prevent it working. The HeLa cells are then no longer immortal.
They senesce and die after about twenty-five cell divisions.12
Cancer requires active telomerase. A tumour is invigorated with the biochemical elixir of youth and immortality. Yet cancer is the quintessential disease of ageing. Cancer rates rise steadily with age, more rapidly in some species than others, but still they rise: there is no creature on earth that is less likely to get cancer in old age than in youth. The prime risk factor for cancer is age. Environmental risk factors, such as cigarette smoking, work in part because they accelerate the ageing process: they damage the lungs, which require repair and repair uses up telomere length, thus making the cells
