A damage accumulation model identifies distinct aging regimes across species.

Abstract

Different species age in similar ways but their lifespans differ by orders of magnitude. It is not clear how these similarities and differences arise from the accumulation of damage that underlies aging. Does long lifespan arise from reduced damage production, increased removal or enhanced robustness to damage? Here we apply the saturating removal model-a stochastic model of damage accumulation and removal-and fit it to survival data from well-studied species. Several parameters have near-universal values including ratios of removal rate, noise amplitude and death threshold. The model parameter that best predicts lifespan is the damage production rate, which spans seven orders of magnitude. We identify two distinct aging regimes: ballistic aging where damage production outpaces removal, characterizing yeast, nematodes, flies and mice, and quasi-steady-state aging, where damage tracks a moving set point of balanced production and removal, characterizing humans, dogs, guinea pigs and cats. These results provide a mechanistic model-based basis of comparative aging that awaits experimental validation.