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The hyperfunction theory: An emerging paradigm for the biology of aging

Gems, D; (2022) The hyperfunction theory: An emerging paradigm for the biology of aging. Ageing Research Reviews , 74 , Article 101557. 10.1016/j.arr.2021.101557. Green open access

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Abstract

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 Magalhães (the developmental theory), and their capacity to make sense of diverse experimental findings is assessed.

Type: Article
Title: The hyperfunction theory: An emerging paradigm for the biology of aging
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.arr.2021.101557
Publisher version: https://doi.org/10.1016/j.arr.2021.101557
Language: English
Additional information: This research was funded in whole, or in part, by the Wellcome Trust Investigator Award (215574/Z/19/Z). For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission.
Keywords: Antagonistic pleiotropy, Hyperfunction, Insulin/IGF-1 signalling, Programmatic aging, Quasi-programs, Theories of aging, mTOR
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Genetics, Evolution and Environment
URI: https://discovery.ucl.ac.uk/id/eprint/10142577
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