Dietary Restriction Impacts Peripheral Circadian Clock Output Important for Longevity inDrosophila

Abstract

Circadian clocks may mediate lifespan extension by caloric or dietary restriction (DR). We find that the core clock transcription factor Clock is crucial for a robust longevity and fecundity response to DR in Drosophila. 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.

Temperature-driven coordination of circadian transcriptional regulation

“…We further posit that the increased coordination of gene expression activity (i.e., the greater organization of cycling genes with respect to the network) may be advantageous for enhancing metabolic efficiency under suboptimal conditions (“suboptimal” in the sense that enzymatic activity will be reduced at 18°C due to Arrhenius scaling, and that D. melanogaster are observed to prefer 25°C [ 26 , 55 ]). This conjecture is supported by other work [ 58 ] showing that circadian regulation of gene expression is necessary for flies to adapt to lower–nutrient conditions. In that study, flies given a 5% sucrose–yeast solution (vs. 15%, as in our study) exhibited lifespan elongation, but only when they had a functioning clock; Clk mutant flies, which lack behavioral and transcriptional rhythms, showed no change in lifespan as a function of dietary restriction.…”