The hidden costs of dietary restriction: implications for its evolutionary and mechanistic origins

Dietary restriction (DR) extends life span across taxa. Despite considerable research, universal mechanisms of DR have not been identified, limiting its translational potential. Guided by the conviction that DR evolved as an adaptive, pro-longevity physiological response to food scarcity, biomedical science has interpreted DR as an activator of pro-longevity molecular pathways. Current evolutionary theory predicts that organisms invest in their soma during DR, and thus when resource availability improves, should outcompete rich-fed controls in survival and/or reproduction. Testing this prediction in Drosophila melanogaster (N > 66,000 across 11 genotypes), our experiments revealed substantial, unexpected mortality costs when flies returned to a rich diet following DR. The physiological effects of DR should therefore not be interpreted as intrinsically pro-longevity, acting via somatic maintenance. We suggest DR could alternatively be considered an escape from costs incurred under nutrient-rich conditions, in addition to costs associated with DR.Funding provided by: American Federation*Crossref Funder Registry ID: Award Number: GR5290420Funding provided by: National Institute on AgingCrossref Funder Registry ID: http://dx.doi.org/10.13039/100000049Award Number: R37 AG024360Funding provided by: National Institute on AgingCrossref Funder Registry ID: http://dx.doi.org/10.13039/100000049Award Number: T32 AG 41688Funding provided by: Natural Environment Research CouncilCrossref Funder Registry ID: http://dx.doi.org/10.13039/501100000270Award Number: M005941Funding provided by: Natural Environment Research CouncilCrossref Funder Registry ID: http://dx.doi.org/10.13039/501100000270Award Number: N013832Funding provided by: American FederationCrossref Funder Registry ID: Award Number: GR5290420Csvs have been broken down by experimental date and analysis, for ease of use