Maximal human lifespan in light of a mechanistic model of aging
Why has maximal human lifespan barely changed in the past two centuries? To understand this we make a mechanistic link between cellular damage, survival curves, and maximum lifespan using a validated stochastic model of damage accumulation and extensive human data. We show that maximal lifespan is set mainly by damage production and clearance rates, as in progeroid syndromes. In contrast, lifestyle factors such as exercise, nutrition, and sleep chiefly reduce stochastic noise and raise the damage level compatible with survival, shifting the median but not the maximum. Similar constraints arise in other mortality models. Our analysis predicts that lifestyle can extend maximal lifespan by at most [~]1 year; substantial gains will require directly perturbing damage production or removal, suggesting specific molecular targets.