Mutation Accumulation Underpins Evolution of Lifespan Extension by Dietary Restriction

Dietary restriction (DR) extends lifespan in animals and plants, but its evolutionary causes are elusive. The prevailing explanation is that DR prolongs life by shifting resources from reproduction to somatic maintenance. To test this idea in Caenorhabditis elegans we developed an experimental paradigm that tricks nematodes into increasing their reproductive effort under DR via food odour cues. Although DR improved survival, experimentally increased reproduction under DR did not reduce either immediate or long-term survival benefits, thus contradicting resource allocation theory. Our results suggest that much of the fertility suppression under DR reflects restraint from reproducing in a poor environment. We developed a model based on Hamilton's forces of selection showing that lifespan extension under DR can evolve because DR suppresses fertility, thereby directly increasing selection against mortality in that environment. Our novel analytical approach demonstrates that DR-driven lifespan extension can evolve under a broader range of conditions than previously anticipated, such as a relaxed need for physiological or genetic trade-offs. Instead, we show how reduced survival on plentiful food can evolve via mutation accumulation.