Editing Senescence (section)

====Mutation accumulation====
{{Main|Mutation accumulation theory}}
[[Natural selection]] can support lethal and harmful [[allele]]s, if their effects are felt after reproduction. The geneticist [[J. B. S. Haldane]] wondered why the dominant mutation that causes [[Huntington's disease]] remained in the population, and why natural selection had not eliminated it. The onset of this neurological disease is (on average) at age 45 and is invariably fatal within 10–20 years. Haldane assumed that, in human prehistory, few survived until age 45. Since few were alive at older ages and their contribution to the next generation was therefore small relative to the large cohorts of younger age groups, the force of selection against such late-acting deleterious mutations was correspondingly small. Therefore, a [[genetic load]] of late-acting deleterious mutations could be substantial at [[mutation–selection balance]]. This concept came to be known as the [[selection shadow]].<ref>{{cite web  |title=The Evolution of Aging |vauthors=Fabian D, Flatt T |date=2011 |work=Nature Education |url=https://core.ac.uk/download/pdf/190039034.pdf}}</ref>

[[Peter Medawar]] formalised this observation in his [[Evolution of ageing#Mutation accumulation|mutation accumulation theory]] of aging.<ref>{{Cite journal| vauthors = Medawar PB |year=1946 |title=Old age and natural death |journal=Modern Quarterly |volume=1 |pages=30–56}}</ref><ref>{{harvnb|Medawar|1952}}{{Page needed|date=September 2010}}</ref> "The force of natural selection weakens with increasing age—even in a theoretically immortal population, provided only that it is exposed to real hazards of mortality. If a genetic disaster... happens late enough in individual life, its consequences may be completely unimportant". Age-independent hazards such as predation, disease, and accidents, called '[[extrinsic mortality]]', mean that even a population with [[negligible senescence]] will have fewer individuals alive in older age groups.