According to this theory, persons loaded with a deleterious mutation have fewer chances to reproduce if the deleterious effect of this mutation is expressed earlier in life. For example, patients with progeria, a genetic disease with symptoms of premature ageing, live for only about 12 years and, therefore, cannot pass their mutant genes to subsequent generations. In such conditions, the progeria is only due to new mutations and is not from the genes of parents. By contrast, people expressing a mutation at older ages can reproduce before the illness occurs; such as is the case with familial Alzheimer’s disease. As an outcome, progeria is less frequent than late diseases such as Alzheimer’s because the mutant genes responsible for the Alzheimer’s disease are not removed from the gene pool as readily as progeria genes, and can thus accumulate in successive generations. In other words, the mutation accumulation theory correctly predicts that the frequency of genetic diseases should increase at older ages.
A second theory postulates that there might be genes whose expression is harmful in later life, but which are not silent earlier in life because they are actually beneficial to survival or reproductive fitness, and have some beneficial effects. Such mutations could thus have a selective advantage in early life and then a negative one later on. These genes will be maintained in the population due to their positive effect on reproduction at young ages despite their negative effects at old post-reproductive age, and their negative effects in later life will look exactly like the ageing process. Suppose, for example, that there is a gene increasing the fixation of calcium in bones. Such a gene may have positive effects early in life because the risk of bone fracture and subsequent death is decreased, but such a gene may have negative effects later in life because of increased risk of osteoarthritis due to excessive calcification. In the wild, such a gene has no actual negative effect because most animals die long before its negative effects can be observed. There is thus a trade-off between an actual positive effect at a young age, and a potential negative one at old age; this negative effect may become effective only if animals live in protected environments such as zoos or laboratories. Costly ornaments of male birds to attract females are essential for reproduction but a burden in later life—peacocks have limited mobility.
Although these concepts as to how mutations can cause ageing have guided attempts to merge evolutionary theory with empirical studies of the biology of ageing, there is little evidence of cumulative mutations that give rise to ageing, and only rare examples of genes that display the necessary early and late functions have been found. These theories do explain the universal occurrence of ageing. But they do not explain the actual process of ageing.
Ageing is best understood as the result of accumulation of random molecular damage in cells for a variety of causes—essentially errors due to wear and tear, and the mechanisms that cause this, and that involve damage to genes and proteins which the cells are unable to reliably repair, will be discussed next. These chance events occur in all body cells, and there are some mechanisms to repair the damage. An exception to such damage is in the germ cells that give rise to the next generation. Germ cells dare not suffer age-related damage, as if they did there would soon be no future healthy offspring. Evolution knows this and ensures that they do not age. By contrast, body cells do age, and evolution only cares to limit this so that reproduction can occur. Evolution selects those cellular activities that delay ageing until reproduction is completed.
Explaining ageing in these terms is partly based on an idea of Weismann, who dropped his theory that ageing was adaptive, and then suggested that ageing evolved because organisms separate in their body those organs involved in reproduction, particularly those that give rise to germ cells—eggs and sperm—from the rest of the body. They invest heavily in those organs involved in reproduction, and this neglect of the body results in ageing. Support for this is found in model organisms, where fertility and lifespan are closely linked. In the nematode C. elegans, cutting out of germline precursor cells of the gonad abolishes reproduction but extends lifespan, as do mutations that reduce germline proliferation. In the fruit-fly D. melanogaster, a reduction in reproduction extends lifespan in females, and certain long-lived mutant females exhibit reduced egg laying, with some being almost sterile. Certain mice that have mutations causing dwarfism are long-lived and sterile.
Researchers have also found that ageing and lifespan do evolve in subsequent generations of biological species in a theoretically predicted direction, depending on particular living conditions. For example, selection for later reproduction—artificial selection of late-born progeny for further breeding—produced, as expected, longer-lived fruit flies, while placing animals in a more dangerous environment with high extrinsic mortality redirected evolution, as predicted, to a shorter lifespan in subsequent generations. Selection of eggs from older flies progressively led to much older flies which lived twice as long.
This all fits with Thomas Kirkwood’s disposable soma theory, where soma refers to the body. The power of selection fades with age. The disposable soma theory argued that ‘it may be selectively advantageous for higher organisms to adopt an energy saving strategy of reduced accuracy in somatic cells to accelerate development and reproduction, but the consequence will be eventual deterioration and death’. Given finite resources, the more the body spends on maintenance of the body, the less it can spend on reproduction. Molecular proofreading is reduced and so are other accuracy-promoting devices in body cells. Energy must be devoted to germ cell reliability but damage can accumulate in body cells—there are so few germ cells by comparison. From the point of view of evolution, the prevention of ageing is only necessary until the animals have reproduced and cared for the young sufficiently well; nature has therefore provided repair measures to delay the process until that is done. According to this theory, we and other animals are disposable once reproduction and the rearing of children have been completed.
Pacific salmon of both sexes do not care for the young and they die a few weeks after spawning. The male marsupial mouse dies after intense spawning from immune system collapse, but not the female. There are also animals that live well past their reproductive period—including whales and human females. In both cases this is due to their looking after and nursing the young, their own as well as those of others in the case of whales.
There is overwhelming evidence that there are strong genetic influences on the rate of ageing. Perhaps the most compelling evidence is that the differences of rates of ageing within individuals of a species are negligible compared with the vast differences across species. Honeybee workers live only a few weeks compared to the queen, who lives for years because she was fed honey when a larva. A mayfly moults, reproduces and dies within a single day, in some cases with a functional lifespan measured in hours; by contrast, giant tortoises can live for over 150 years, helped probably by their protective armour. The powerful influence of genetics is further reflected by the ever increasing number of single-gene mutations that can influence the lifespan of organisms ranging from yeast to mice.