Editorials

How can we live forever?

Of course living forever is a myth--sooner or later an accident would catch up with us even if we did not age. But there has been considerable discussion recently of the idea that the human life span might be extended.¹ Much of this discussion can be dismissed as wild optimism, but there are some geneticists who seem willing to extrapolate from work on invertebrates to suggest that 200 year human life spans may be on the horizon.² To understand the status of these claims we need to look at current knowledge of the biology of aging and, in particular, the role of genetics. It has long been held that the best recipe for a long life is to choose your parents well, and a study on longevity records in a sample of 19th century Danish twins has estimated that genetic influences are responsible for about a fifth of the variance in life span.³

What kinds of genes influence aging, how many of them are there likely to be, and can we alter their functions to intervene in the aging process? At this point it should be said, loudly and clearly, that the primary goal of research on the biological basis of aging must be to enhance the quality of later years of life. If quality is not improved, any increase in quantity might prove to be a Pyrrhic victory.

Evolutionary genetics tells us much about the kinds of genes likely to control aging.⁴ These will not be "clocks" that count out our allotted span and then activate to destroy us. The reason is that natural selection is not much concerned with old age. Animals in the wild do not live long enough to grow old, and the evolution of specific death mechanisms is implausible. Instead, evolutionary theory suggests that aging comes about through trade offs, the most important of which involve the costs and benefits of maintenance. We need maintenance to keep us alive, but maintenance is expensive. It requires lots of energy that could otherwise be used for faster growth and reproduction, both of which enhance Darwinian fitness. The upshot is that the body, or "soma," is expected to tune its maintenance levels to be good enough to get through the normal expectation of life in the "wild" environment in reasonably sound condition, but not so good as to last forever. In other words, the soma is disposable.⁵

Having a disposable soma was not a problem when life was nasty, brutish, and short but it is a trifle inconvenient now, when the human race has triumphed over the hazards of the environment to such an extent that most of us live long enough to experience the downside of our limited investment in maintenance.

If aging is due to imperfect maintenance, and there is growing evidence that it is, there is hope that interventions can be developed to slow the onset of age associated diseases by reducing the burden of damage or by enhancing maintenance functions. The complexity will be considerable. After all, evolutionary theory itself predicts that the number of genes will be large. There are many different maintenance systems, and each of these systems involves multiple genes. Genes interact in networks within cells,⁶ cells interact within organs, and organs interact within the body. The potential for synergy is immense.

The value of a genetic understanding of aging is clear, but interventions need not be genetic. For example, regular athletic exercise is associated with a slowing of the accumulation of mutant mitochondria seen in muscle cells with advancing age.⁷ If the association proves to be one of causality, then the fault involves genes but the remedy does not. Drugs being developed against Alzheimer's disease capitalise on genetic insights but do not, as yet, target the genes themselves.⁸

The picture we need to define is of how genes, environments, and lifestyles work together to influence longevity and health in old age. This will not come easily, but come it will if we go at it hard enough. Increasing human life spans to 200 years may take a little longer.

Gerontologist Department of Geriatric Medicine, University of Manchester, Manchester M13 9PT

Tom Kirkwood 

1. Concar D. Death of old age. New Scientist 1996 June 22: 24-9.
2. Gladwell M. Heaven can wait. Independent Magazine 1996 November 23: 11-20.
3. McGue M, Vaupel JW, Holm N, Harvald B. Longevity is moderately heritable in a sample of Danish twins born 1870-1880. J Gerontol 1993;48:B237-44.
4. Kirkwood TBL. Human senescence. BioEssays 1996;18:1009-16. [Medline]
5. Kirkwood TBL. The evolution of ageing. Rev Clin Gerontol 1396;5:3-9.
6. Kowald A, Kirkwood TBL. A network theory of ageing: the interactions of defective mitochondria, aberrant proteins, free radicals and scavengers in the ageing process. Mutat Res 1996;316:209-36. [Medline]
7. Brierley EJ, Johnson MA, James OFW, Turnbull DM. Effects of physical activity and age on mitochondrial function. Q J Med 1996;89:251-8. [Abstract]
8. Marx J. Searching for drugs that combat Alzheimer's. Science 1996;273:50-3. [Medline]