Time-restricted feeding prolongs lifespan in Drosophila in a peripheral clock-dependent manner

Abstract Time-restricted feeding/eating (TRF/TRE) – limiting not the amount of food but the daily time window of food intake – is a dietary intervention that has been shown to improve health markers in model organisms and humans, but whether these benefits translate into positive effects on aging and longevity is not clear. We demonstrate here that TRF robustly prolongs lifespan in the short-lived genetically tractable model organism Drosophila melanogaster . Median TRF lifespan extensions range between ∼10% and ∼50% dependent on sex, reproductive status, TRF duration, and genotype. TRF’s positive effect on longevity is independent of food intake and at least in part relies on a functioning circadian clock: TRF benefits on longevity are abolished in arrhythmic per 0 and tim 01 mutants as well as in constant light, suggesting that timed feeding acts as a zeitgeber partitioning eating and associated metabolic processes into certain phases of day and night. TRF-mediated longevity extension is unaffected in flies whose neural circadian clocks have been abolished genetically, pointing towards peripheral clocks as the target of TRF mediating lifespan extension.