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Lookup NU author(s): Dr James Wordsworth,
Dr Peter Clark,
Dr Daryl Shanley
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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.
Author(s): Wordsworth J, OKeefe H, Clark P, Shanley D
Publication type: Article
Publication status: Published
Journal: Mechanisms of Aging and Development
Print publication date: 01/10/2022
Online publication date: 20/07/2022
Acceptance date: 17/07/2022
ISSN (print): 0047-6374
ISSN (electronic): 1872-6216
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