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protein 1, or T E P 1 . But it looks as if this protein, although a vital ingredient of telomerase, is not the bit that does the actual reverse transcription to repair the ends of chromosomes. A better candidate for that function has since been found but, as of this writing, its genetic location is still uncertain.4
Between them, these telomerase genes are as close as we may get to finding the 'genes for youth'. Telomerase seems to behave like the elixir of eternal life for cells. Geron Corporation, a company devoted to telomerase research, was founded by the scientist who first showed that telomeres shrink in dividing cells, Cal Harley.
Geron hit the headlines in August 1997 for cloning part of telomerase. Its share price promptly doubled, not so much on the hope that it could give us eternal youth as on the prospect of making anti-cancer drugs: tumours require telomerase to keep them growing.
But Geron went on to immortalise cells with telomerase. In one experiment, Geron scientists took two cell types grown in the laboratory, both of which lacked natural telomerase, and equipped them with a gene for telomerase. The cells continued dividing, vigorous and youthful, far beyond the point where they would normally senesce and die. At the time the result was published the cells that had had the telomerase gene introduced had exceeded their expected lifespan by more than twenty doublings, and they showed no sign of slowing down.5
In normal human development, the genes that make telomerase are switched off in all but a few tissues of the developing embryo.
The effect of this switching off of telomerase has been likened to the setting of a stopwatch. From that moment the telomeres count the number of divisions in each cell line and at a certain point they reach their limit and call a halt. Germ cells never start the stopwatch
- they never switch off the telomerase genes. Malignant tumour cells switch the genes back on. Mouse cells in which one of the telomerase genes has been artificially 'knocked out' have progressively shorter telomeres.6
The lack of telomerase seems to be the principal reason that cells grow old and die, but is it the principal reason bodies grow old and 2 0 0 G E N O M E
die? There is some good evidence in favour: cells in the walls of arteries generally have shorter telomeres than cells in the walls of veins. This reflects the harder lives of arterial walls, which are subject to more stress and strain because arterial blood is under higher pressure. They have to expand and contract with every pulse beat, so they suffer more damage and need more repair. Repair involves cell copying, which uses up the ends of telomeres. The cells start to age, which is why we die from hardened arteries, not from hardened veins.7
The ageing of the brain cannot be explained so easily, because brain cells do not replace themselves during life. Yet this is not fatal to the telomere theory: the brain's support cells, called glial cells, do indeed duplicate themselves; their telomeres do, therefore, probably shrink. However, there are very few experts who now believe that ageing is, chiefly, the accumulation of senescent cells, cells with abridged telomeres. Most of the things we associate with ageing -
cancer, muscle weakness, tendon stiffness, hair greyness, changes in skin elasticity - have nothing to do with cells failing to duplicate themselves. In the case of cancer, the problem is that cells are copying themselves all too enthusiastically.
Moreover, there are huge differences between different species of animal in the rate at which they age. On the whole, bigger animals, such as elephants, live longer than smaller animals, which is at first sight puzzling given that it takes more cell doublings to make an elephant than a mouse — if cell doublings lead to senescent cells.
And lethargic, slow-lived animals such as tortoises and sloths are long-lived for their size. This led to a neat generalisation, which is so tidy it ought to be true and probably would be if physicists ran the world: every animal has roughly the same number of heartbeats per lifetime. An elephant lives longer than a mouse, but its pulse rate is so much slower that, measured in heartbeats, they both live lives of the same length.
The trouble is, there are damning exceptions to the rule: notably bats and birds. Tiny bats can live for at least thirty years, during almost all of which they eat, breathe and pump blood at a frantic I M M O R T A L I T Y 2 0 I
rate — and this applies even in species that do not hibernate. Birds —
whose blood is several degrees hotter, whose blood sugar is at least twice as concentrated and whose oxygen consumption is far faster than in most mammals - generally live long lives. There is a famous pair of photographs of the Scottish ornithologist George Dunnet holding the same wild fulmar petrel in 1950 and 1992. The fulmar looks exactly the same in the two pictures; Professor Dunnet doesn't.
Fortunately, where the biochemists and medics have failed to explain ageing patterns, the evolutionists have come to the rescue.
J. B. S. Haldane, Peter Medawar and George Williams separately put together the most satisfying account of the ageing process.
Each species, it seems, comes equipped with a program of planned obsolescence chosen to suit its expected life-span and the age at which it is likely to have finished breeding. Natural selection carefully weeds out all genes that might allow damage to the body before or during reproduction. It does so by killing or lowering the reproductive success of all individuals that express such genes in youth.
All the rest reproduce. But natural selection cannot weed out genes that damage the body in post-reproductive old age, because there is no reproduction of the successful in old age. Take Dunnet's fulmar, for instance. The reason it lives far longer than a mouse is because in the life of the fulmar there is no equivalent of the cat and the owl: no natural predators. A mouse is unlikely
Evidence for this theory comes from a natural experiment studied by Steven Austad on an island called Sapelo, which lies about five miles off the coast of Georgia in the United States. Sapelo contains a population of Virginia opossums that has been isolated for 10,000
years. Opossums, like many marsupials, age very rapidly. By the age of two years, opossums are generally dead from old age - the victims of cataracts, arthritis, bare skin and parasites. But that hardly matters because by two they have generally been hit by a truck, a coyote, 2 0 2 G E N O M E
an owl or some other natural enemy. On Sapelo, reasoned Austad, where many predators are absent, they would live longer and so —
