Evolutionary causes of lifespan extension by dietary restriction: linking theory and mechanisms

Dietary restriction (DR), reduced food intake without malnutrition, increases lifespan across a broad range of taxa, but the evolutionary underpinning of this phenomenon is poorly understood. The resource reallocation hypothesis proposes that dietary restricted animals divert resources from reproduction to somatic maintenance to increase survival in times of nutrient scarcity in favour of future reproduction. The “longevity by-product” hypothesis proposes instead that dietary restricted animals increase nutrient recycling via autophagy to maximise immediate reproduction, thereby reducing cellular toxic waste and leading to longer lifespan as an unselected by-product. The “longevity by-product” hypothesis makes a unique prediction that blocking autophagy in DR animals will simultaneously reduce lifespan and reproduction. To test the adaptive value of autophagy under dietary restriction, we inhibited autophagy using bec-1 RNAi knockdown in DR and fully-fed Caenorhabditis elegans nematodes. Our findings confirm that autophagic inhibition results in a significantly shorter lifespan under DR, suggesting that autophagy is important for survival in times of famine. Remarkably, we also show that inhibiting autophagy throughout adult life significantly increases reproduction in both dietary restricted and fully fed worms. Moreover, this did not come at a transgenerational cost to offspring fitness. Our results suggest that autophagy is an energetically costly process that reduces resources available for reproduction, but is necessary for survival during famine, and are thus consistent with the resource reallocation hypothesis.