Introduction to Evolutionary Theories of Aging and Longevity
Evolutionary theories of aging and longevity are those theories that try to explain the remarkable differences in observed aging rates and longevity/life span across different biological species through interplay between the processes of DNA (gene) mutation and selection. In addition to mutation and selection, the reproductive cost, or, more generally, the trade-offs between different traits of organisms may also contribute to the evolution of species aging and longevity. Since evolutionary theories of aging are closely related to the genetics of aging, and because most of our knowledge at present on the molecular mechanisms of human aging are derived from experimental findings across a wide range of biological species, we include the introductory discussion of this topic under “Programmed Epigenomic Theory of Aging”, the interested reader can visit our resource section for additional review articles devoted specifically for this topic.
Three major evolutionary theories of aging are as follows: 1) the theory of programmed death by August Weismann, 2) the mutation accumulation theory of aging by Peter Medawar, and 3) the antagonistic pleiotropy theory of aging by George Williams. Initial idea of the programmed death theory of aging was that “there exists a specific death-mechanism designed by natural selection to eliminate the old, and therefore worn-out, members of a population. The purpose of this programmed death of the old is to clean up the living space and to free up resources for younger generations”.Suggesting the theory of programmed death, Weismann had to think about the exact biological mechanisms for this death program and came to an idea that there is a specific limitation on the number of divisions that somatic cells might undergo which later became known as the Hayflick limit, was ultimately confirmed.
The triumph of Weismann’s idea of a cell division limit did not help, however, to justify his theory of programmed death. The cells stopped dividing, but no programmed cell death occurred. Moreover, the hypothesis was put forward that this cell growth arrest is in fact beneficial for organism survival because it protects against cancer. It was also suggested that the cell division limit may have relevance to another evolutionary theory of aging: the antagonistic pleiotropy theory, which will be discussed later. However his later dispoable soma theory was generally accepted. Disposable Soma Theory State: – Somatic cells are maintained only to ensure continued reproductive success, following reproduction the soma is disposable.
“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 (i.e., avoid extinction). Current evolutionary explanations of aging and limited longevity of biological species are based on two major evolutionary theories: the mutation accumulation theory and the antagonistic pleiotropy theory.
Mutation accumulation theory: 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 80 will experience no selection because people with this mutation will have already passed it to their offspring by that age. Over successive generations, late-acting deleterious mutations will accumulate, leading to an increase in mortality rates late in life.”
Antagonistic pleiotropy theory or “Play Later” Theory propose that 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. “The theory of antagonistic pleiotropy is based on two assumptions. First, it is assumed that a particular gene may have an effect not on one trait only but on several traits of an organism (pleiotropy). The second assumption is that these pleiotropic effects may affect individual fitness in opposite (antagonistic) ways. This antagonistic pleiotropy theory was proposed by George Williams, who noticed that “natural selection may be said to be biased in favor of youth over old age whenever a conflict of interests arises.”
According to Williams, this conflict arises from “pleiotropic genes that have opposite effects on fitnesses at different ages.…Selection of a gene that confers an advantage at one age and a disadvantage at another will depend not only on the magnitudes of the effects themselves, but also on the times of the effects. An advantage during the period of maximum reproductive probability would increase the total reproductive probability more than a proportionately similar disadvantage later on would decrease it. So natural selection will frequently maximize vigor in youth at the expense of vigor later on and thereby produce a declining vigor (aging) during adult life”. These initially verbal arguments of George Williams were later proved mathematically by Brian Charlesworth.
In other words, Williams suggested the existence of so-called pleiotropic genes (demonstrating favorable effects on fitness at young ages and deleterious ones at old age) that could explain the aging process. Such genes will be maintained in the population due to their positive effect on reproduction at young ages despite their negative effects at old postreproductive age (their negative effects in later life will look exactly like the aging process).
For the purpose of illustration, suppose 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 then 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.
Another example of antagonistic pleiotropy refers to replicative cellular senescence (cell division limit), which is known to suppress tumorigenesis by switching cells into a state of arrested growth. This very process that suppresses tumorigenesis early in life, however, may promote cancer in later life because senescent cells stimulate other premalignant and malignant cells to proliferate and to form tumors. Here again there is a trade-off between the earlier protective effect of growth arrest because of cellular senescence and the later detrimental effect caused by cancer promotion.
The antagonistic pleiotropy theory explains why reproduction may come with a cost for species longevity and may even induce death (see the story on bamboo plants and “suicidal” salmon life cycles at the beginning of this article). Indeed, any mutations favoring more intensive reproduction (more offspring produced) will be propagated in future generations even if these mutations have some deleterious effects in later life. For example, mutations causing overproduction of sex hormones may increase the sex drive, libido, reproductive efforts, and success, and therefore they may be favored by selection despite causing prostate cancer (in males) and ovarian cancer (in females) later in life. Thus, the idea of reproductive cost, or more generally of trade-offs, between different traits of the organism follows directly from antagonistic pleiotropy theory.”
