Evolution of ageing

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The aging of the leaf. You can see yellowing and drying, which begins from the outer edge.

Enquiry into the evolution of ageing aims to explain why survival, reproductive success, and functioning of almost all living organisms decline at old age. Leading hypotheses[1][2] suggest that a combination of limited resources, and environmental causes determine an "optimal" level of repair regarding molecular and cellular level damage that accumulates over time. This process is known as self-maintenance.

Theories and hypotheses[edit]

The beginning[edit]

August Weismann 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.[3] The idea that the ageing characteristic was selected (an adaptation) 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.[4] Weismann later abandoned his theory and later followed up with his "programmed death" theory.

Mutation accumulation[edit]

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. 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.[5]

Medawar's theory is referred to as Mutation Accumulation. This theory is based on the idea that random, germline mutations occur that are detrimental to overall health and survival later in life. Overall, senescence would occur through a summation of deleterious mutations, and would explain the overall phenotypic damage we associate with ageing.[6][7][8][9]

Antagonistic pleiotropy[edit]

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.'[1] 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.[10]

Williams eventually proposed his own hypothesis called antagonistic pleiotropy. Pleiotropy, alone, means one mutation that cause multiple effects on phenotype.[11] Antagonistic pleiotropy on the other hand deals with one gene that creates two traits with one being beneficial and the other being detrimental. In essence, this refers to genes that offer benefits early in life, but accumulate a cost later on.[1]

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.[12]

Disposable soma theory[edit]

A third mainstream theory of ageing, the ''Disposable soma theory, proposed in 1977 by Thomas Kirkwood, presumes that the body must budget the resources available to it. The body uses resources derived from the environment for metabolism, for reproduction, and for repair and maintenance, and the body must compromise when there is a finite supply of resources. The theory states that this compromise causes the body to reallocate energy to the repair function that causes the body to gradually deteriorate with age.[13]

A caveat to this theory suggests that this reallocation of energy is based on time instead of limiting resources. This concept focuses on the evolutionary pressure to reproduce in a set, optimal time period that is dictated by age and ecological niche. The way that this is successful is through the allocation of time and energy in damage repair at the cellular level resulting in an accumulation of damage and a decreased lifespan relative to organisms with longer gestation. This concept stems from a comparative analysis of genomic stability in mammalian cells.[14]

One opposing argument is based on caloric restriction (CR) effect, which has demonstrated an increase in life.[15][16][17] But dietary restriction has not been shown to increase lifetime reproductive success (fitness), because when food availability is lower, reproductive output is also lower. Moreover, calories are not the only resource of possibly limited supply to an organism that could have an effect on multiple dimensions of fitness.

DNA damage/error theory[edit]

The DNA damage theory of aging postulates that DNA damage is ubiquitous in the biological world and is the primary cause of ageing.[18] The theory is based off the idea that ageing occurs over time due to the damage of the DNA. As an example, studies of mammalian brain and muscle have shown that DNA repair capability is relatively high during early development when cells are dividing mitotically, but declines substantially as cells enter the post-mitotic state.[19][20][21] The effect of reducing expression of DNA repair capability is increased accumulation of DNA damage. This impairs gene transcription and causes the progressive loss of cellular and tissue functions that define aging.

Damage theories suggest that external/environmental factors cause damage to cells over time through a number of various methods. One such theory is the free radical or rate of living theory which relies on the assumption that the speed at which an organism is able to metabolize oxygen is directly correlated to the release of destructive atoms which break down the cell. The destructive atoms, known as free radicals, are released during oxygen basal metabolism and collide with healthy cells material causing breakdown, and eventual cell death. All organisms have this oxygen basal metabolism, however it is the rate at which oxygen is broken down that determines the rate at which cells die. For Instance, a fly has an incredible metabolic rate, so because of this they expend oxygen quickly causing cell hastened cell death which can explain their life span of only 2-3 weeks.[citation needed]

Programmed maintenance theories[edit]

Theories, such as Weismann's "programmed death" theory, suggest that deterioration and death due to ageing are a purposeful result of an organism's evolved design, and are referred to as theories of programmed ageing or adaptive ageing.

The programmed maintenance theory based on evolvability[22] suggests that the repair mechanisms are controlled by a common control mechanism capable of sensing conditions, such as caloric restriction, and may be responsible for lifespan in particular species. In this theory, the survival techniques are based on control mechanisms instead of individual maintenance mechanism, which you see in the non-programmed theory of mammal ageing.

A non-programmed theory of mammal ageing[23] states that different species possess different capabilities for maintenance and repair. Longer-lived species possess many mechanisms for offsetting damage due to causes such as oxidation, telomere shortening, and other deteriorative processes. Shorter-lived species, having earlier ages of sexual maturity, have less need for longevity and thus did not evolve or retain the more-effective repair mechanisms. Damage therefore accumulates more rapidly, resulting in earlier manifestations and shorter lifespan. Since there are a wide variety of ageing manifestations that appear to have very different causes, it is likely that there are many different maintenance and repair functions.

Natural selection[edit]

Group selection[edit]

Group selection is based on the idea that all members of a given group will either succeed or fail together depending on the circumstance. With this mechanism, genetic drift occurs collectively to all in the group and sets them apart from other groups of its own species. This is different than individual selection, as it focuses on the group rather than the individual.[24]

Often also postreproductive individuals make intergenerational transfers: bottlenose dolphins and pilot whales guard their grandchildren; there is cooperative breeding in some mammals, many insects and about 200 species of birds; sex differences in the survival of anthropoid primates tend to correlate with the care to offspring; or an Efe infant is often attended by more than 10 people. Lee developed a formal theory integrating selection due to transfers (at all ages) with selection due to fertility.[25]


Evolvability is based on the idea that an organism adapts genetically to its present environment.

Skulachev (1997)[26] has suggested that programmed ageing assists the evolution process by providing a gradually increasing challenge or obstacle to survival and reproduction, and therefore enhancing the selection of beneficial characteristics.

Goldsmith (2008)[27] proposed that though increasing the generation rate and evolution rate is beneficial for a species, it is also important to limit lifespan so older individuals will not dominate the gene pool.

Yang (2013)'s model[4] is also based on the idea that ageing accelerates the accumulation of novel adaptive genes in local populations. However, Yang changed the terminology of "evolvability" into "genetic creativity" throughout his paper to facilitate the understanding of how ageing can have a shorter-term benefit than the word "evolvability" would imply.

Lenart and Vašku (2016) [28] have also invoked evolvability as the main mechanism driving evolution of ageing. However, they proposed that even though the actual rate of aging can be an adaptation the aging itself is inevitable. In other words, evolution can change the speed of aging but some ageing no matter how slow will always occur.


There are two types of mortality: intrinsic and extrinsic mortality. Intrinsic mortality is thought to be a result of ageing from insider factors, whereas extrinsic is a direct result of environmental factors. An example would be that bats have fewer predators, and therefore have a low extrinsic mortality. Birds are warm-blooded and are similar in size to many small mammals, yet often live 5–10 times as long. They have less predation pressure than ground-dwelling mammals, and have a lower extrinsic mortality.[29]

When examining the body-size vs. lifespan relationship, one also observes that predatory mammals tend to live longer than prey mammals in a controlled environment, such as a zoo or nature reserve. The explanation for the long lifespans of primates (such as humans, monkeys, and apes) relative to body size is that their intelligence, and they would have a lower intrinsic mortality.[30]



Progeria is a single-gene genetic disease that cause acceleration of many or most symptoms of ageing during childhood. Those who have this disease are known for failure to thrive and have a series of symptoms that cause abnormalities in the joints, hair, skin, eyes, and face.[31] Although the term progeria applies strictly speaking to all diseases characterized by premature aging symptoms, and is often used as such, it is often applied specifically in reference to Hutchinson–Gilford progeria syndrome (HGPS).

Werner Syndrome[edit]

Werner syndrome, also known as "adult progeria", is another single-gene genetic disease. This syndrome starts to affect individuals during the teenage years, preventing teens from growing at puberty. Once the individual reaches the twenties, there is generally a change in hair color, skin, and voice. This condition can also affect the weight distribution between the arms, legs, and torso.[32]


Theories of ageing affect efforts to understand and find treatments for age-related conditions:

  • Those who believe in the idea that ageing is an unavoidable side effect of some necessary function (antagonistic pleiotropy or disposable soma theories) logically tend to believe that attempts to delay ageing would result in unacceptable side effects to the necessary functions. Altering ageing is therefore "impossible",[1] and study of ageing mechanisms is of only academic interest.
  • Those believing in default theories of multiple maintenance mechanisms tend to believe that ways might be found to enhance the operation of some of those mechanisms. Perhaps they can be assisted by antioxidants or other agents.
  • Those who believe in programmed ageing suppose that ways might be found to interfere with the operation of the part of the ageing mechanism that appears to be common to multiple symptoms, essentially "slowing down the clock" and delaying multiple manifestations. Such effect might be obtained by fooling a sense function. One such effort is an attempt to find a "mimetic" that would "mime" the anti-ageing effect of calorie restriction without having to actually radically restrict diet.[33]

See also[edit]


  1. ^ a b c d Williams, George C. (December 1957). "Pleiotropy, Natural Selection, and the Evolution of Senescence". Evolution. 11 (4): 398–411. doi:10.1111/j.1558-5646.1957.tb02911.x. JSTOR 2406060.
  2. ^ Kirkwood, T. B. L. (November 1977). "Evolution of ageing". Nature. 270 (5635): 301–4. Bibcode:1977Natur.270..301K. doi:10.1038/270301a0. PMID 593350.
  3. ^ Weismann A. (1889). Essays upon heredity and kindred biological problems. Oxford: Clarendon Press. Work that describes Weismann's theory about making room for the young.
  4. ^ a b Yang J (2013). "Viscous populations evolve altruistic programmed ageing in ability conflict in a changing environment". Evolutionary Ecology Research. 15: 527–543.
  5. ^ Fabian D, Flatt T (2011). "The Evolution of Aging". Scitable. Nature Publishing Group. Retrieved May 20, 2014.
  6. ^ Medawar PB (1952). An Unsolved Problem of Biology. London: H.K. Lewis.
  7. ^ Edney EB, Gill RW (October 1968). "Evolution of senescence and specific longevity". Nature. 220 (5164): 281–2. doi:10.1038/220281a0. PMID 5684860.
  8. ^ Monaco TO, Silveira PS (May 2009). "Aging is not senescence: a short computer demonstration and implications for medical practice". Clinics. 64 (5): 451–7. doi:10.1590/S1807-59322009000500013. PMC 2694250. PMID 19488612.
  9. ^ Edney EB, Gill RW (October 1968). "Evolution of senescence and specific longevity". Nature. 220 (5164): 281–2. Bibcode:1968Natur.220..281E. doi:10.1038/220281a0. PMID 5684860. Further describes theory of mutation accumulation.
  10. ^ Carter AJ, Nguyen AQ (December 2011). "Antagonistic pleiotropy as a widespread mechanism for the maintenance of polymorphic disease alleles". BMC Medical Genetics. 12: 160. doi:10.1186/1471-2350-12-160. PMC 3254080. PMID 22151998.
  11. ^ Curtsinger, J.W. (2001). "Senescence: Genetic Theories". International Encyclopedia of the Social & Behavioral Sciences. pp. 13897–902. doi:10.1016/B0-08-043076-7/03374-X. ISBN 978-0-08-043076-8.
  12. ^ Leroi AM, Chippindale AK, Rose MR (August 1994). "Long-term laboratory evolution of a genetic life-history tradeoff in Drosophila melanogaster. 1. The role of genotype-by-environment interaction". Evolution; International Journal of Organic Evolution. 48 (4): 1244–1257. doi:10.1111/j.1558-5646.1994.tb05309.x. PMID 28564485.
  13. ^ Kirkwood TB (November 1977). "Evolution of ageing". Nature. 270 (5635): 301–4. Bibcode:1977Natur.270..301K. doi:10.1038/270301a0. PMID 593350. Origin of the disposable soma theory.
  14. ^ Lorenzini A, Stamato T, Sell C (November 2011). "The disposable soma theory revisited: time as a resource in the theories of aging". Cell Cycle. 10 (22): 3853–6. doi:10.4161/cc.10.22.18302. PMID 22071624.
  15. ^ Weindruch R, Walford IL (1986). The Retardation of Aging and Disease by Dietary Restriction. Springfield, IL: Thomas.
  16. ^ Weindruch R (1996). "The retardation of aging by caloric restriction: studies in rodents and primates". Toxicologic Pathology. 24 (6): 742–5. doi:10.1177/019262339602400618. PMID 8994305.
  17. ^ Masoro EJ (September 2005). "Overview of caloric restriction and ageing". Mechanisms of Ageing and Development. 126 (9): 913–22. doi:10.1016/j.mad.2005.03.012. PMID 15885745. Overview of caloric restriction and aging.
  18. ^ Gensler HL, Bernstein H (September 1981). "DNA damage as the primary cause of aging". The Quarterly Review of Biology. 56 (3): 279–303. doi:10.1086/412317. PMID 7031747.
  19. ^ Gensler HL (1981). "Low level of U.V.-induced unscheduled DNA synthesis in postmitotic brain cells of hamsters: possible relevance to aging". Experimental Gerontology. 16 (2): 199–207. doi:10.1016/0531-5565(81)90046-2. PMID 7286098.
  20. ^ Karran P, Moscona A, Strauss B (July 1977). "Developmental decline in DNA repair in neural retina cells of chick embryos. Persistent deficiency of repair competence in a cell line derived from late embryos". The Journal of Cell Biology. 74 (1): 274–86. doi:10.1083/jcb.74.1.274. PMC 2109876. PMID 559680.
  21. ^ Lampidis TJ, Schaiberger GE (December 1975). "Age-related loss of DNA repair synthesis in isolated rat myocardial cells". Experimental Cell Research. 96 (2): 412–6. doi:10.1016/0014-4827(75)90276-1. PMID 1193184.
  22. ^ Goldsmith T (2009). "Mammal aging: active and passive mechanisms". Journal of Bioscience Hypotheses. 2 (2): 59–64. doi:10.1016/j.bihy.2008.12.002. Article compares programmed and non-programmed maintenance theories of ageing in light of empirical evidence.
  23. ^ Holliday R (May 2006). "Aging is no longer an unsolved problem in biology". Annals of the New York Academy of Sciences. 1067 (1): 1–9. Bibcode:2006NYASA1067....1H. doi:10.1196/annals.1354.002. PMID 16803964.
  24. ^ Mitteldorf, J. (2006). "Chaotic population dynamics and the evolution of ageing: proposing a demographic theory of senescence". Evolutionary Ecology Research. 8: 561–74. On population dynamics as a mechanism for the evolution of ageing.
  25. ^ Lee RD (August 2003). "Rethinking the evolutionary theory of aging: transfers, not births, shape senescence in social species". Proceedings of the National Academy of Sciences of the United States of America. 100 (16): 9637–42. doi:10.1073/pnas.1530303100. PMC 170970. PMID 12878733.
  26. ^ Skulachev VP (November 1997). "Aging is a specific biological function rather than the result of a disorder in complex living systems: biochemical evidence in support of Weismann's hypothesis". Biochemistry. Biokhimiia. 62 (11): 1191–5. PMID 9467841.
  27. ^ Goldsmith TC (June 2008). "Aging, evolvability, and the individual benefit requirement; medical implications of aging theory controversies". Journal of Theoretical Biology. 252 (4): 764–8. doi:10.1016/j.jtbi.2008.02.035. PMID 18396295.
  28. ^ Lenart P, Bienertová-Vašků J (August 2017). "Keeping up with the Red Queen: the pace of aging as an adaptation". Biogerontology. 18 (4): 693–709. doi:10.1007/s10522-016-9674-4. PMID 28013399.
  29. ^ Koopman JJ, Wensink MJ, Rozing MP, van Bodegom D, Westendorp RG (July 2015). "Intrinsic and extrinsic mortality reunited". Experimental Gerontology. 67: 48–53. doi:10.1016/j.exger.2015.04.013. PMID 25916736.
  30. ^ Shokhirev MN, Johnson AA (2014-01-21). "Effects of extrinsic mortality on the evolution of aging: a stochastic modeling approach". PLOS ONE. 9 (1): e86602. doi:10.1371/journal.pone.0086602. PMC 3897743. PMID 24466165.
  31. ^ "Hutchinson-Gilford progeria syndrome". Genetics Home Reference. Retrieved 2019-03-27.
  32. ^ Navarro CL, Cau P, Lévy N (October 2006). "Molecular bases of progeroid syndromes". Human Molecular Genetics. 15 (suppl_2): R151–61. doi:10.1093/hmg/ddl214. PMID 16987878.
  33. ^ Chen D, Guarente L (February 2007). "SIR2: a potential target for calorie restriction mimetics". Trends in Molecular Medicine. 13 (2): 64–71. doi:10.1016/j.molmed.2006.12.004. PMID 17207661.


Further reading[edit]

  • Gavrilova NS, Gavrilov LA, Semyonova VG, Evdokushkina GN (June 2004). "Does exceptional human longevity come with a high cost of infertility? Testing the evolutionary theories of aging". Annals of the New York Academy of Sciences. 1019 (1): 513–7. Bibcode:2004NYASA1019..513G. CiteSeerX doi:10.1196/annals.1297.095. PMID 15247077.
  • Gavrilova NS, Gavrilov LA (2005). "Human longevity and reproduction: An evolutionary perspective.". In Voland E, Chasiotis A, Schiefenhoevel W (eds.). Grandmotherhood - The Evolutionary Significance of the Second Half of Female Life. New Brunswick, NJ, USA: Rutgers University Press. pp. 59–80.
  • Gavrilova NS, Gavrilov LA (2002). "Evolution of Aging". In Ekerdt DJ (ed.). Encyclopedia of Aging. 2. New York: Macmillan Reference USA. pp. 458–467.
  • Gavrilov LA, Gavrilova NS (February 2002). "Evolutionary theories of aging and longevity". TheScientificWorldJournal. 2: 339–56. doi:10.1100/tsw.2002.96. PMC 6009642. PMID 12806021.
  • Gavrilova NS, Gavrilov LA, Evdokushkina GN, Semyonova VG, Gavrilova AL, Evdokushkina NN, Kushnareva YE, Kroutko VN (August 1998). "Evolution, mutations, and human longevity: European royal and noble families". Human Biology. 70 (4): 799–804. PMID 9686488.

External links[edit]

  1. ^ Jin, Kunlin (2010-08-01). "Modern Biological Theories of Aging". Aging and Disease. 1 (2): 72–74. ISSN 2152-5250. PMC 2995895. PMID 21132086.