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.
Tom Kirkwood
Gerontologist Department of Geriatric Medicine,
University of
Manchester,
Manchester M13 9PT
References:
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 J W, 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 T B L. Human senescence. BioEssays
1996;18:1009-16.
5 Kirkwood T B L. The evolution of ageing. Rev Clin
Gerontol 1396;5:3-9.
6 Kowald A, Kirkwood T B L. 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.
7 Brierley E J, Johnson
MA, James OFW, Turnbull DM. Effects of physical activity and age on mitochondrial function.
Q J Med 1996;89:251-8.
8 Marx J. Searching for drugs that combat
Alzheimer's. Science 1996;273:50-3.
