Dietary Restriction Impacts Peripheral Circadian Clock Output Important for Longevity inDrosophila

Abstract

AbstractCircadian clocks may mediate lifespan extension by caloric or dietary restriction (DR). We find that the core clock transcription factorClockis crucial for a robust longevity and fecundity response to DR inDrosophila. To identify clock-controlled mediators, we performed RNA-sequencing from abdominal fat bodies across the 24 h day after just 5 days under control or DR diets. In contrast to more chronic DR regimens, we did not detect significant changes in the rhythmic expression of core clock genes. Yet we discovered that DR induced de novo rhythmicity or increased expression of rhythmic clock output genes. Network analysis revealed that DR increased network connectivity in one module comprised of genes encoding proteasome subunits. Adult, fat body specific RNAi knockdown demonstrated that proteasome subunits contribute to DR-mediated lifespan extension. Thus, clock control of output links DR-mediated changes in rhythmic transcription to lifespan extension.