Dietary Restriction Impacts Peripheral Diurnal Rhythms Important for Longevity in Drosophila
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 daily rhythmicity or increased expression of oscillating 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, daily gene regulation links DR-mediated changes in rhythmic transcription to lifespan extension.
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Research summary
The paper claims that the core circadian clock factor Clock and proteasome subunits are necessary for dietary restriction to extend lifespan in Drosophila. This is relevant because it identifies specific molecular mechanisms (circadian regulation of proteasome activity) that mediate a known longevity intervention, offering potential targets for understanding how metabolic and temporal cues interact to influence aging.
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