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.