Abstract
Dietary restriction (DR) consistently and universally extends health- and lifespan across taxa. Despite considerable research, precise and universal mechanisms of DR have not been identified, limiting the translational potential of its beneficial outcomes to humans. In biomedical science, DR’s effects are interpreted as stimulating pro-longevity molecular pathways. This rationale is guided by the conviction that DR evolved as an adaptive, pro-longevity physiological response to restricted food supply. Current evolutionary theory states that organisms should invest in their soma more heavily during periods of DR, and, when their resource availability improves, should outcompete age-matched rich-fed controls in survival and/or reproduction. Here we present a formal test of this key prediction utilising a large-scale demographic approach detailing mortality and fecundity in Drosophila melanogaster fed alternating dietary regimes (N > 66,000 flies across 11 genetic lines). Our experiments reveal substantial, unexpected mortality costs when returning to a rich diet following periods of DR, in direct contrast to the predictions from current evolutionary theory of DR. The physiological effects of DR should therefore not be interpreted as being intrinsically pro-longevity, acting through increased investment in somatic maintenance. We suggest DR’s effects could alternatively be considered an escape from costs incurred under nutrient-rich conditions, in addition to novel, discrete costs associated with DR. Our results therefore question the relevance of DR’s current evolutionary explanation in interpreting its mechanistic basis.