Evolution of ageing
Enquiry into the evolution of ageing, or aging, aims to explain why a detrimental process such as ageing would evolve, and why there is so much variability in the lifespans of organisms. The classical theories of evolution suggest that environmental factors, such as predation, accidents, disease, and/or starvation, ensure that most organisms living in natural settings will not live until old age, and so there will be very little pressure to conserve genetic changes that increase longevity. Natural selection will instead strongly favor genes which ensure early maturation and rapid reproduction, and the selection for genetic traits which promote molecular and cellular self-maintenance will decline with age for most organisms.
Theories and hypotheses
The beginning
was responsible for interpreting and formalizing the mechanisms of Darwinian evolution in a modern theoretical framework. In 1889, he theorized that ageing was part of life's program to make room for the next generation in order to sustain the turnover that is necessary for evolution. The idea that the ageing characteristic was selected because of its deleterious effect was largely discounted for much of the 20th century, but a theoretical model suggests that altruistic ageing could evolve if there is little migration among populations. Weismann later abandoned his theory and after some time followed up with his "programmed death" theory.Natural selection is a process that allows organisms to better adapt to the environment, it is the survival of the fittest which are predicted to produce more offsprings. Natural selection acts on life history traits in order to optimize reproductive success and lifetime fitness. Fitness in this context refers to how likely an organism is to survive and reproduce. It is based on the environment and is also relative to other individuals in the population. Examples of life history traits include; age and size at first reproduction, number of size and offsprings produced, and the period of reproductive lifespan. Organisms put energy into growth, reproduction, and maintenance by following a particular pattern which changes throughout their lifetime due to the trade-offs that exist between the different energy allocations. Investment in current vs future reproduction, for example, comes at the expense of the other. Natural selection, however is not so effective on organisms as they age. Mutation accumulation and antagonistic pleiotropy are two factors which contribute to senescence. Both MA, and AP contribute to age-related declines in fitness. The accumulation of random, germline age-related mutated alleles is known as mutation accumulation. Note that somatic mutations are not heritable, they are only a source of developmental variation. Studies done on Drosophila melanogaster have shown that mutation accumulation drives the combination of alleles which have "age-specific additive effects" that cause a decline in stress response and ultimately an age-related decline in fitness. The number of germ cell divisions per generation is variable among lineages, and relates to genome size; for humans; 401 germ cell divisions occur per generation in males and 31 in females.
Mutation accumulation
Germ line
The first modern theory of mammal ageing was formulated by Peter Medawar in 1952. This theory formed in the previous decade with J. B. S. Haldane and his selection shadow concept. The development of human civilization has shifted the selective shadow as the conditions that humans now live in include improved quality of food, living conditions, and healthcare. This improved healthcare includes modern medicine such as antibiotics and new medical technology. A few studies in Drosophila have shown that the age of expression of novel deleterious mutations, defines the effects they contribute on mortality. Overall, however; although their frequency increases, their effects and variation decreases with age.There is no theory that explains how these deleterious mutations affect fitness on different ages and the evolution of senescence. Their idea was that ageing was a matter of neglect, as nature is a highly competitive place. Almost all animals die in the wild from predators, disease, or accidents, which lowers the average age of death. Therefore, there is not much reason why the body should remain fit for the long haul because selection pressure is low for traits that would maintain viability past the time when most animals would have died anyway. Metabolic diseases come along due to the low demand for physical activity in modern civilization compared to times where humans had to forage in the wild for survival. With the selective shadow now shifted, humans must deal with these new selective pressures.
Senescence is considered a by-product of physiology because our cell metabolism creates products that are toxic, we get mutations when we age, and we don't have enough stem cells that regenerate. Why did selection not find and favor mutations in ways that allow us, for example, to regenerate our cells, or to not produce toxic metabolism? Why did menopause evolve? Because selection is more efficient on traits that appear early in life. Mutations that have an effect early in life will increase fitness much more than mutations that manifest late. Most people have already reproduced before any disease manifest; this means that parents will pass their alleles to their offsprings before they show any fitness problems, and it is therefore "too late" for selection.
The two theories; non-adaptive, and adaptive, are used to explain the evolution of senescence, which is the decline in reproduction with age. The non-adaptive theory assumes that the evolutionary deterioration of human age occurs as a result of accumulation of deleterious mutations in the germline. These deleterious mutations start expressing themselves late in life, by the time we are weak/wobbly and have already reproduced, this means that Natural selection cannot act on them because reproduction has ended. Studies done on Drosophila melanogaster have shown an inverse relationship between the mean optimal age at maturity and mutation rates per gene. Mutation accumulation affects the allocation of energy, and time that are directed towards growth and reproduction over the lifetime of an organism, especially the period of reproductive lifespan due to the fact that mutation accumulation accelerates senescence, this means that organisms must reach the optimum age of maturity at a younger age as their reproductive lifespan is shortened with accumulated mutation.
Mutations happen, and they are completely random with respect to a need in the environment and fitness. Mutations can either be beneficial in which they increase an organism's fitness, neutral in which they do not affect an organism's fitness or deleterious where they negatively affect an organism's fitness. Previously done experiments have shown that most mutation accumulations are deleterious, and just a few are beneficial. Mutations of genes that interact with one another during the developmental process create biological and, thus, phenotypical diversities. Mutations is genetic information that are expressed among organisms via gene expression, which is the translation of genetic information into a phenotypic character. Evolution is the change in a heritable trait in a population across generations since mutations generate variations in the heritable traits; they are considered the raw material for evolution. Therefore, beneficial mutation accumulations during the developmental processes could generate more phenotypic variations, which increases their gene frequency and affect the capacity of phenotypic evolution.
Somatic cells
The somatic mutation theory of ageing states that accumulation of mutations in somatic cells is the primary cause of aging. A comparison of somatic mutation rate across several mammal species found that the total number of accumulated mutations at the end of lifespan was roughly equal across a broad range of lifespans. The authors state that this strong relationship between somatic mutation rate and lifespan across different mammalian species suggests that evolution may constrain somatic mutation rates, perhaps by selection acting on different DNA repair pathways.Antagonistic pleiotropy
Medawar's theory was critiqued and later further developed by George C. Williams in 1957. Williams noted that senescence may be causing many deaths even if animals are not 'dying of old age.' He began his hypothesis with the idea that ageing can cause earlier senescence due to the competitive nature of life. Even a small amount of ageing can be fatal; hence natural selection does indeed care and ageing is not cost-free.Williams eventually proposed his own hypothesis called antagonistic pleiotropy. Pleiotropy, alone, means one mutation that cause multiple effects on phenotype. Antagonistic pleiotropy on the other hand deals with one gene that creates two traits with one being beneficial and the other detrimental. In essence, this refers to genes that offer benefits early in life, but later accumulate a cost. In other words, antagonistic pleiotropy is when the resultant relationship between two traits is negative. It's when one phenotypic trait positively affects current reproduction at the expense of later accelerated senescence, growth, and maintenance. Antagonistic pleiotropy is permanent unless a mutation that modifies the effects of the primary locus occurs.
Although antagonistic pleiotropy is a prevailing theory today, this is largely by default, and has not been well verified. Research has shown that this is not true for all genes and may be thought of as partial validation of the theory, but it cuts the core premise: that genetic trade-offs are the root cause of ageing.
In breeding experiments, Michael R. Rose selected fruit flies for long lifespan. Based on antagonistic pleiotropy, Rose expected that this would surely reduce their fertility. His team found that they were able to breed flies that lived more than twice as long as the flies they started with, but to their surprise, the long-lived, inbred flies actually laid more eggs than the short-lived flies. This was another setback for pleiotropy theory, though Rose maintains it may be an experimental artifact.