How to live for ever

DEATH is a fact of life—at least it has been so far. Humans grow old. From early adulthood, performance starts to wane. Muscles become progressively weaker, cognition fails. But the point at which age turns to ill health and, ultimately, death is shifting—that is, people are remaining healthier for longer. And that raises the question of how death might be postponed, and whether it might be postponed indefinitely.

Humans are certainly living longer. An American child born in 1970 could expect to live 70.8 years. By 2000, that had increased to 77 years. Moreover, an adult still alive at the age of 75 in 2002 could expect a further 11.5 years of life.

Much of this change has been the result of improved nutrition and better medicine. But to experience a healthy old age also involves maintaining physical and mental function. Age-related non-pathological changes in the brain, muscles, joints, immune system, lungs and heart must be minimised. These changes are called “senescence”.

Research shows that exercise can help to maintain physical function late in life and that exercising one's brain can limit the progression of senescence. Other work—on the effects of caloric restriction, consuming red wine and altering genes in yeast, mice and nematodes—has shown promise in slowing senescence.

The approach advocated by Aubrey de Grey of the University of Cambridge, in England, and presented at last week's meeting of the American Association for the Advancement of Science, is rather more radical. As an engineer, he favours intervening directly to repair the changes in the body that are caused by ageing. This is an approach he dubs “strategies for engineered negligible senescence”. In other words, if ageing humans can be patched up for 30 years, he argues, science will have developed sufficiently to make further repairs more effective, postponing death indefinitely.

Dr de Grey's ideas, which are informed by literature surveys rather than experimental work, have been greeted with scorn by those working at developing such repair kits. Steven Austad, a gerontologist based at the University of Texas, warns that such therapies are many years away and may never arrive at all. There are also the side effects to consider. While mice kept on low-calorie diets live longer than their fatter friends, the skinny mice are less fertile and are sometimes sterile. Humans wishing both to prolong their lives and to procreate might thus wish to wait until their child-bearing years were behind them before embarking on such a diet, although, by then, relatively more age-related damage will have accumulated.

No one knows exactly why a low-calorie diet extends the life of mice, but some researchers think it is linked to the rate at which cells divide. There is a maximum number of times that a human cell can divide (roughly 50) before it dies. This is because the ends of chromosomes, structures called telomeres, shorten each time the cell divides. Eventually, there is not enough left for any further division.

Cell biologists led by Judith Campisi at the Lawrence Berkeley National Laboratory in California doubt that every cell has this dividing limit, and believe that it could be only those cells that have stopped dividing that cause ageing. They are devising an experiment to create a mouse in which senescent cells—those that no longer divide—are prevented from accumulating. They plan to activate a gene in the mouse that will selectively eliminate senescent cells. Such a mouse could demonstrate whether it is possible to avoid growing old.

But successful ageing is being promoted here and now. Older people who engage in a lot of social interactions stay young for their chronological age, argues John Rowe, a professor of medicine and geriatrics at the Mount Sinai School of Medicine in New York. Research has shown that people who receive emotional support not only have higher physical performance than their isolated counterparts, but also that they show lower levels of hormones that are associated with stress.

Other work, led by Teresa Seeman of the University of California, Los Angeles, shows that “allostatic load”—the cumulative physiological toll exacted on the body—predicts life expectancy well. It is measured using variables including blood pressure and levels of stress hormones.

Dr Seeman found that elderly people with high degrees of social engagement had lower allostatic loads. They were also more likely to be well educated and to have a high socio-economic status. It would thus appear that death can be postponed by various means and healthy ageing extended by others. Whether death will remain the ultimate consequence of growing old remains to be seen.

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