On aging and age-specific effects of spontaneous mutations

Abstract

Evolutionary theory assumes that mutations that cause aging either have beneficial early-life effects that gradually become deleterious with advancing age (antagonistic pleiotropy [AP]) or that they only have deleterious effects at old age (mutation accumulation [MA]). Mechanistically, aging is predicted to result from damage accumulating in the soma. While this scenario is compatible with AP, it is not immediately obvious how damage would accumulate under MA. In a modified version of the MA theory, it has been suggested that mutations with weakly deleterious effects at young age can also contribute to aging, if they generate damage that gradually accumulates with age. Mutations with increasing deleterious effects have recently gained support from theoretical work and studies of large-effect mutations. Here we address if spontaneous mutations also have negative effects that increase with age. We accumulate mutations with early-life effects in Drosophila melanogaster across 27 generations and compare their relative effects on fecundity early and late in life. Our mutation accumulation lines on average have substantially lower early-life fecundity compared to controls. These effects were further maintained throughout life, but they did not increase with age. Our results suggest that most spontaneous mutations do not contribute to damage accumulation and aging.

Keywords: Drosophila melanogaster; age-specific effects; aging; mutation accumulation; positive pleiotropy; spontaneous mutations.