Evolution of Ageing - Mutation Accumulation

Mutation Accumulation

The first modern, successful theory of mammal aging was formulated by Peter Medawar in 1952. His idea was that aging was a matter of neglect. Nature is a highly competitive place, and almost all animals in nature die before they attain old age. Therefore, there is not much reason why the body should remain fit for the long haul - not much selection pressure for traits that would maintain viability past the time when most animals would be dead anyway, killed by predators or disease or by accident.

Medawar's theory is referred to as Mutation Accumulation. The mechanism of action involves random, detrimental mutations of a kind that happen to show their effect only late in life. Unlike most detrimental mutations, these would not be efficiently weeded out by natural selection. Hence they would 'accumulate' and, perhaps, cause all the decline and damage that we associate with aging.

Modern genetics science has disclosed a possible problem with the mutation accumulation concept in that it is now known that genes are typically expressed in specific tissues at specific times (see regulation of gene expression). Expression is controlled by some genetic "program" that activates different genes at different times in the normal growth, development, and day-to-day life of the organism. Defects in genes cause problems (genetic diseases) when they are not properly expressed when required. A problem late in life suggests that the genetic program called for expression of a gene only in late life and the mutational defect prevented proper expression. This implies existence of a program that called for different gene expression at that point in life. Why, given Medawar's concept, would there exist genes only needed in late life or a program that called for different expression only in late life? The maintenance mechanism theory (discussed below) avoids this problem.

Medawar's concept suggested that the evolution process was affected by the age at which an organism was capable of reproducing. Characteristics that adversely affected an organism prior to that age would severely limit the organism's ability to propagate its characteristics and thus would be highly "selected against" by natural selection. Characteristics that caused the same adverse effects that only appeared well after that age would have relatively little effect on the organism's ability to propagate and therefore might be allowed by natural selection. This concept fit well with the observed multiplicity of mammal life spans (and differing ages of sexual maturity) and is important to all of the subsequent theories of aging discussed below.

Medawar did not suggest that there were fundamental limitations on life span. Organisms exhibiting negligible senescence suggest that aging is not a fundamental limitation, at least not in the scale of mammal life span.