Sex-specific mutation accumulation: A parsimonious explanation for sex differences in lifespan and ageing

Jacob A. Moorad, Tracey Chapman, Alexei A. Maklakov

Sex differences in lifespan and ageing pervade the tree of life, yet their evolutionary origin is still debated. Adaptive trade-off models have long dominated the field but show mixed empirical support. Here we argue that sex-specific mutation accumulation is the most parsimonious evolutionary cause of sex-biased ageing. Because anisogamy and ecology shape reproductive and survival schedules, natural selection weakens faster in one sex than in the other. The sex with the fastest declines in selection gradients with age will accumulate a greater load of late-acting deleterious mutations, leading to faster ageing and shorter lifespans. Critically, this mechanism works without requiring sex-specific resource allocation or genetic trade-offs. Therefore, it can resolve previously puzzling and contradictory variation observed in experimental and comparative studies because its predictions are context-dependent according to prevailing demographic patterns. Because this model requires only sex-biased gene expression and differences in late-age reproductive contributions towards future generations, it is sufficient to explain sexual dimorphism in lifespan and ageing across organisms with different sex determination systems. We discuss existing empirical support for this new model and outline approaches to test its predictions and quantify the role of sex-specific mutation accumulation in the evolution of sex differences in lifespan and ageing.