Population size shapes the evolution of lifespan

Biological aging results from the age-dependent change in the force of natural selection, which increases the probability of germline variants that limit survival to accumulate in genes acting predominantly in late life1. The evolutionary mechanisms underlying the accumulation of neutral mutations and antagonistically pleiotropic gene variants that cause biological aging have been analyzed to date under the assumption of infinitely large population size. However, even though population size importantly shapes genetic and phenotype variation via drift and selection2,3, we still have a limited understanding of how finite population size impacts the evolution of mortality at the population level. Here, we study the impact of population size on lifespan evolution under mutation accumulation and antagonistic pleiotropy. We found that larger population size leads to lower age-independent, as well as age-dependent mortality under mutation accumulation, due to more effective purifying selection against deleterious germline variants. Strikingly, large population size can lead to extended lifespan under antagonistic pleiotropy, due to more effective positive selection on gene variants increasing survival in early-life, while leading to increased post-maturation mortality. Our findings provide a comprehensive numerical framework for the two major evolutionary genetic theories of aging and reveal a fundamental and yet non-appreciated role for population size in the evolution of mortality trajectories.