The damage-independent evolution of ageing by selective destruction

Abstract

Ageing is currently believed to reflect the accumulation of molecular damage due to energetic costs of maintenance, as proposed in disposable soma theory (DST). Here we have used 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 fast-growing mutants might necessitate a mechanism of counterselection we name selective destruction, which removes the faster growing cells from the tissue, preventing the threat of morbidity and mortality they pose. As a result, the survival advantage would shift to the slower cells, allowing them to spread, inducing 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. If true, negligible senescence would acquire a new meaning of increased basal mortality.

Cell Senescence-Independent Ageing of Human Skin

“…Our data from normalisation of ΔCT by value at time zero suggests that adult cells are still capable of similar scale increases in production of mRNA as neonatal cells; but from a smaller starting value the end result is still lower. This may reflect that similar fold change is easier from lower starting values, and thus ageing cells might still have reduced capacity, but another possibility is that homeostasis has shifted toward reduced ECM production and slower metabolism, consistent with a different model of ageing we have recently described as selective destruction theory (SDT) (Wordsworth et al, 2022). SDT predicts that many cells will undergo a reduction in metabolism that may manifest in lower basal rates of anabolic activity such as ECM production.…”