By William Carter
Every aspect of our biology is ultimately determined by the millions of years of evolution that has shaped it; the discerning and patient hand of natural selection working over countless generations to sculpt our every feature and trait. Our mortality, the apparent absolute antithesis of an advantageous attribute, is a product of this process. Why exactly, is a question disputed to this day.
A seminal step towards understanding the evolutionary bases of ageing was made in 1952 by Peter Medawar(Medawar, 1952), who observed that the force of natural selection declines with age.
We can explain this by thinking of natural selection acting on mutations according to their effect on an individual’s overall reproductive success. For example, a mutation that halts puberty will be vigorously selected against, as it rules out any chance of having offspring; conferring no reproductive success whatsoever. On the other hand, a mutation that effectively sterilises individuals over the age of 40 will not be selected against as forcefully, as the carriers are likely to have already reproduced, so the effect of the mutation on their reproductive success is reduced.
Take, for example, Huntington’s disease, a deadly neurological genetic disorder. The disease slowly kills off brain cells, causing the gradual neurological decline of the patient; an incurable genetic condition whose respective mutation you’d think would be selected fiercely against. Huntington’s, however, is heritable. This is thought to be because the disease only begins to manifest symptoms between the ages of 30-50 years. By this time the carrier of the mutation is likely to have already been reproductively successful, and so have passed the mutation to their offspring. The Huntington’s mutation, therefore, experiences much less selective pressure against it than you might have thought, due to its late-acting nature.
Having recognised and articulated this phenomenon of natural selection, Medawar built upon the basis it provided to propose his theory of Mutation Accumulation (MAt).
Mutation Accumulation Theory states that because of the lack of selective pressure against them, late-acting, deleterious mutations accumulate in a population over time, resulting in increased mortality in later life due to the gradual deterioration of cellular and metabolic processes as these mutations manifest themselves. Medawar’s theory has more recently been refined and expressed mathematically by Charlesworth (Charlesworth, 1994).
Despite the ‘sense’ such a theory seems to make, there exists little conclusive evidence to support Medawar’s theory. A theory with a greater body of evidence to support it, however, is that of Antagonistic Pleiotropy, proposed by George Williams (Williams, 1957).
Williams first assumes that there exist particular genes which influence not just one, but multiple traits in an organism, called pleiotropic genes. It is also assumed that, among these pleiotropic genes, there exist those with effects beneficial at earlier ages, but other effects harmful at later ages – meaning the genes have opposite (antagonistic) effects. Williams reasons that, rather than natural selection neglecting older individuals, as Medawar’s theory suggests, ageing is simply a trade-off between the different effects of pleiotropic genes acting over the course of an organism’s lifespan.
The Antagonistic Pleiotropy theory states that a pleiotropic mutation with a beneficial effect in youth, yet a detrimental effect in later life will be selected for.
This is because, according to Williams, “natural selection may be said to be biased in favour of youth over old age whenever a conflict of interests arises”. In the eyes of natural selection, the pleiotropic mutation’s benefit to reproductive success in youth outweighs its harmful effects in later life.
Let’s look again at Huntington’s disease, which we know is caused by an inherited mutation that results in the gradual neurodegeneration of the patient. Interestingly, recent research has shown that this same mutation greatly increases the activity of a tumour-suppressing protein called p53. The increased expression of this protein results in lower rates of cancer among Huntington’s patients, which can help improve reproductive success. Huntington’s disease is a prime example of Williams’ theory; the mutation is selected for because its overall effect on reproductive success is positive.
Williams made several testable predictions using his theory, which have been tested to varying degrees of success in experiments using Drosophila, a species of fruit fly. Williams predicted that: “Successful selection for increased longevity should result in decreased fitness (ability to reproduce) in youth.” The work of Rose with Drosophila has demonstrated a close relationship between longevity and fitness in early life, supporting Williams’ prediction (Rose, 1991). In the experiments, selection for reduced lifespans improved early-life fitness and thus, reproductive success, whereas selection for longer lifespans reduced fitness in youth, so reducing reproductive success.
Other predictions made by Williams’ have been less successful, experiments testing them often returning inconclusive results. Even the above experiment by Rose, must be viewed with a critical lens. While Rose’s results have been repeated, the continued use of Drosophila in almost all experiments testing these evolutionary hypotheses suggests that any results, such as Rose’s, may only apply to Drosophila. Evolutionary experiments with mammals are far less common, for example, and though they have shown there are trade-offs between fitness and longevity, the relationships are much less distinct than that of Drosophila.
Very similar to Williams’ theory in respect to the idea of trade-offs is Kirkwood’s Disposable Soma Theory.
In his 1977 paper “Evolution of Ageing”, Kirkwood, though accepting the precedent upon which Medawar and Williams base their theories, tackles the problem of ageing from a different perspective in the formulation of his own.
Kirkwood views the life of an individual as an investment of resources (energy, matter, etc…) in the creation and maintenance of a soma (body) in return for reproductive success. Due to uncontrollable environmental risks, it can be assumed that every individual will have a finite lifespan and as such, no investment in the maintenance of a soma will prevent the inevitable death of the individual. Acknowledging this, Kirkwood reasons reproductive success is maximised when the level of resources invested in maintenance is less than would be required for indefinite survival.
The concept is best expressed by the man himself:
“Too low an investment in the prevention or repair of somatic damage is obviously a mistake because then the individual may disintegrate too soon. However, too high an investment in maintenance is also wasteful because there is no advantage in maintaining the soma better than is necessary to survive the expected lifetime in the wild environment in reasonably sound condition, and excess investment in maintenance will reduce the resources available for growth and reproduction.”
Natural selection acts on genes regulating maintenance and repair to strike a balance between longevity and reproduction. The evolved limitations placed on the maintenance of the body and its systems allows for the accumulation of damage over time that results eventually in death.
All three theories try to explain why we age and thus why we die from an evolutionary standpoint. Common to the theories is the understanding that ageing is not a process that has been selected for, but rather a by-product of the evolution of other aspects of our biology. The selective pressure simply does not exist to solve all the little problems in our genome and biology that bring about our inevitable physiological descent into the grave. Callous and cold though it may sound, I conclude that we die because it is not evolutionarily beneficial to continue to live.
References:
Medawar, P. 1952. An Unsolved Problem of Biology. London: HK Lewis
Charlesworth, B. 1994. Evolution in Age-Structured Populations. Cambridge: Cambridge University Press.
Williams, G. 1957 Pleiotropy, natural selection, and the evolution of senescence. Evolution 11(4), 398-411.
Rose, M. 1991. Evolutionary Biology of Ageing. New York: Oxford University Press.
Imperial Bioscience Review 