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The damage-independent evolution of ageing by selective destruction

Lookup NU author(s): Dr James Wordsworth, Hannah O'Keefe, Dr Peter Clark, Dr Daryl Shanley

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Abstract

Ageing is widely believed to reflect the accumulation of molecular damage due to energetic costs of maintenance, as proposed in disposable soma theory (DST). Here we use agent-based modelling to describe an alternative theory by which ageing could undergo positive selection independent of energetic costs. We suggest that the selective advantage of aberrant cells with fast growth might necessitate a mechanism of counterselection we name selective destruction that specifically removes the faster cells from tissues, preventing the morbidity and mortality risks they pose. The resulting survival advantage of slower mutants could switch the direction of selection, allowing them to outcompete both fast mutants and wildtype cells, causing them to spread and induce ageing in the form of a metabolic slowdown. Selective destruction could therefore provide a proximal cause of ageing that is both consistent with the gene expression hallmarks of ageing, and independent of accumulating damage. Furthermore, negligible senescence would acquire a new meaning of increased basal mortality.

Publication metadata

Author(s): Wordsworth J, OKeefe H, Clark P, Shanley D

Publication type: Article

Publication status: Published

Journal: Mechanisms of Aging and Development

Year: 2022

Volume: 207

Print publication date: 01/10/2022

Online publication date: 20/07/2022

Acceptance date: 17/07/2022

Date deposited: 26/06/2023

ISSN (print): 0047-6374

ISSN (electronic): 1872-6216

Publisher: Elsevier

URL: https://doi.org/10.1016/j.mad.2022.111709

DOI: 10.1016/j.mad.2022.111709

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