Evolution of Aging

There are remarkable differences in observed aging rates and longevity records across different biological species (compare, for example, mice and humans). These differences are a result of what is known as the evolution of aging, a result of the processes of mutation and selection. The attempt to understand the biological evolution of aging and life span was sparked, in part, by the puzzling life cycles of some biological species. For example, a bamboo plant reproduces vegetatively (asexually) for about one hundred years, forming a dense stands of plants. Then, in one season, all the plants flower simultaneously, reproduce sexually and then die. About one hundred years later the process is repeated. This and the observation of other "suicidal" life cycles of various species, such as salmon, promoted the idea that sexual reproduction may come at the cost of species longevity. Thus, in addition to mutation and selection, the reproductive cost, or, more generally, the trade-offs between different traits of organisms, may contribute to the evolution of species aging and longevity. The evolution of aging is also related to the genetics of aging, because it studies the evolution of heritable manifestations of aging in subsequent generations.

For many decades, the evolution of aging was a puzzling phenomenon, especially in light of the Darwinian theory of evolution by natural selection. Darwin's theory is based on the idea of random and heritable variation of biological traits between individuals (caused by mutations), with subsequent natural selection for preferential reproduction of those individuals who are particularly fit to live in a given environment. Therefore, it is expected (and observed) that biological evolution acts to increase the fitness and performance of species evolving in successive generations. From this optimistic perspective, it was difficult to understand why natural selection seemed to result in such bizarrely injurious features as senescence and late-life degenerative diseases, rather than eternal youth and immortality. How does it happen that the developmental program formed by biological evolution—after having accomplished the miraculous success that leads from a single cell at conception, to a subsequent birth, then to sexual maturity and productive adulthood—fails to maintain the accomplishments of its own work? Another theoretical difficulty in understanding the evolution of aging was the timing problem—many manifestations of aging happen after the reproductive period of evolving organisms, at ages that are beyond the reach of natural selection.

The problem of biological evolution of aging has been studied over the years in a purely theoretical and abstract way by August Weismann (1889), Ronald Fisher (1930), Peter Medawar (1952), George Williams (1957), William Hamilton (1966), Brian Charlesworth (1994) and other researchers. The resulting evolutionary theory of aging has been partially tested by direct evolutionary experiments on laboratory fruit flies and on natural populations of guppies. Researchers found that aging and life span do evolve in subsequent generations of biological species in the expected direction, depending on particular living conditions. For example, a 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 life span in subsequent generations. Therefore, the early criticism of the evolutionary theory of aging as merely a theoretical speculation, with limited and indirect supporting evidence obtained from retrospective and descriptive studies, has been overturned. On the contrary, the evolutionary plasticity of aging and longevity is now an established experimental fact.

The evolutionary theory of aging may be considered as part of a more general life history theory, which tries to explain how evolution designs organisms to achieve reproductive success (that is, to avoid extinction). Life history theory is based on mathematical methods of optimization models with specific biological constraints. Among the questions posed and answered by the life history theory are: Why are organisms small or large? Why do they mature early or late? Why do they have few or many offspring? Why do they have a short or a long life? Why must they grow old and die?

The latter two questions represent the entire scientific agenda of the evolutionary theory of aging. Therefore, it could be said that the evolutionary theory of aging is a subset of the life history theory. On the other hand, the evolutionary theory of aging is considered to be the intellectual core of the biodemography of aging and longevity. Biodemography is a multidisciplinary approach, integrating methods of biological and social sciences in an attempt to explain demographic data (e.g., life tables) and processes (e.g., mortality trends).

Current evolutionary explanations of aging and limited longevity of biological species are based on two major evolutionary theories: the mutation accumulation theory (Medawar) and the antagonistic pleiotropy theory (Williams). These two theories are based on the idea that, from the evolutionary perspective, aging is an inevitable result of the declining force of natural selection with age. For example, a mutant gene that kills young children will be strongly selected against (will not be passed to the next generation), while a lethal mutation with effects confined to people over the age of eighty will experience no selection because people with this mutation will have already passed it to their offspring by that age. So, over successive generations, late-acting deleterious mutations will accumulate, leading to an increase in mortality rates late in life (mutation accumulation theory). Moreover, late-acting deleterious genes may even be favored by selection and be actively accumulated in populations if they have any beneficial effects early in life (antagonistic pleiotropy theory).

Note that these two theories of aging are not mutually exclusive—both evolutionary mechanisms may operate at the same time. The main difference between the two theories is that in the mutation accumulation theory, genes with negative effects at old age accumulate passively from one generation to the next, while in the antagonistic pleiotropy theory these genes are actively kept in the gene pool by selection. The actual relative contribution of each evolutionary mechanism in species aging has not yet been determined, and this scientific problem is now the main focus of research of evolutionary biologists.

Interestingly, since the 1950s no fundamentally new evolutionary theories of aging have been proposed. There have been, however, attempts to find a better name for the antagonistic pleiotropy theory, and to specify in more detail how one and the same gene could have both deleterious and beneficial effects. The disposable soma theory, which was proposed by Thomas Kirkwood in 1977 and developed further by Kirkwood and Robin Holliday in 1979, considered a special class of gene mutations with the following antagonistic pleiotropic effects: mutations that save energy for reproduction (positive effect) and other accuracy promoting devices in somatic cells (negative effect). The authors of 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." While discussing the disposable soma theory, it is important to keep in mind that it was initially proposed to provide evolutionary justification for another (failed) theory of aging—the error catastrophe theory, which considered aging as a result of breakdown in accuracy of macromolecular synthesis within somatic cells. Most researchers agree that the disposable soma theory is a special, more narrowly defined variant of the antagonistic pleiotropy theory of aging. According to Kirkwood and Holliday, "the disposable soma theory is, in a sense, a special case of Williams's (1957) pleiotropic gene hypothesis [antagonistic pleiotropy theory], the gene in question controlling the switch to reduced accuracy in somatic cells. The good effect of the gene is the reduced investment of resources in the soma, while the bad effect is the ultimate somatic disintegration, or ageing."

In addition to legitimate theoretical and experimental studies of the evolution of aging, there is also a more ambitious pro-evolutionary approach that aims "to overthrow the present intellectual order of gerontology [science of aging], and to replace it with one based on evolutionary and genetic foundations" (Rose).

This ambitious pro-evolutionary approach considers all other theories of biological aging— such as the free-radical theory of aging (Beckman and Ames; Harman), the somatic mutation theory of aging (Morley), the reliability theory of aging (Gavrilov and Gavrilova, 1991; 2001), the mitochondrial theory of aging (Gershon), the waste accumulation theory of aging (Terman), and the error catastrophe theory of aging—as far less important to gerontology: "the evolutionary biology of aging, rather than, for example, cell biology, should be the intellectual core of gerontology" (Rose).

Apparently, this ambitious pro-evolutionary doctrine is based on a literal interpretation of the following statement by Theodosius Dobzhansky (1900–1975) : "Nothing in biology makes sense except in the light of evolution" (Rose).

The claim has been made that a simple evolutionary model can explain even the observed age-trajectory of mortality curves, including the late-life mortality plateaus (the tendency of mortality curves to level off at advanced ages), but other investigators have found these claims to be unsubstantiated. Thus, declarations that the evolutionary theory of aging should have a dominating status among other biological theories of aging remain to be justified.