期刊
AGEING RESEARCH REVIEWS
卷 74, 期 -, 页码 -出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.arr.2021.101557
关键词
Antagonistic pleiotropy; Insulin/IGF-1 signalling; Hyperfunction; Quasi-programs; mTOR; Theories of aging; Programmatic aging
资金
- Wellcome Trust Investigator Award [215574/Z/19/Z]
- Wellcome Trust [215574/Z/19/Z] Funding Source: Wellcome Trust
The process of aging is determined by wild-type genes, which are not necessarily adaptive. Two important theories, antagonistic pleiotropy and programmatic development, explain the causes of aging.
The process of senescence (aging) is predominantly determined by the action of wild-type genes. For most organisms, this does not reflect any adaptive function that senescence serves, but rather evolutionary effects of declining selection against genes with deleterious effects later in life. To understand aging requires an account of how evolutionary mechanisms give rise to pathogenic gene action and late-life disease, that integrates evolutionary (ultimate) and mechanistic (proximate) causes into a single explanation. A well-supported evolutionary explanation by G.C. Williams argues that senescence can evolve due to pleiotropic effects of alleles with antagonistic effects on fitness and late-life health (antagonistic pleiotropy, AP). What has remained unclear is how gene action gives rise to late-life disease pathophysiology. One ultimate-proximate account is T.B.L. Kirkwood's disposable soma theory. Based on the hypothesis that stochastic molecular damage causes senescence, this reasons that aging is coupled to reproductive fitness due to preferential investment of resources into reproduction, rather than somatic maintenance. An alternative and more recent ultimate-proximate theory argues that aging is largely caused by programmatic, developmental-type mechanisms. Here ideas about AP and programmatic aging are reviewed, particularly those of M.V. Blagosklonny (the hyperfunction theory) and J.P. de Magalha & SIM;es (the developmental theory), and their capacity to make sense of diverse experimental findings is assessed.
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