View Program - 63rd Annual Drosophila Research Conference

Time-restricted feeding (TRF) has become an anti-aging treatment of great interest in recent years, with the potential to delay aging and improve health in diverse organisms from Drosophila to humans. TRF consists of restricting food intake to specific hours of the day. Because TRF simply controls the timing of feeding rather than nutrient or caloric content, TRF has been hypothesized to depend on circadian-regulated functions including many metabolic functions. Nonetheless, the underlying molecular mechanisms of TRF-mediated metabolic regulation remain unclear. To exploit the rapid genetic tools and well-characterized aging markers of Drosophila, we developed an alternate-day, intermittent TRF (iTRF) dietary regimen for flies that robustly extended their lifespan and delayed aging-dependent processes such as poly-ubiquitinated protein aggregation in muscles and intestinal dysplasia. We showed that iTRF treatment enhanced circadian-regulated transcription and that iTRF-mediated lifespan extension required molecular components of both the circadian clock and autophagy, a well conserved longevity pathway. Night-specific induction of autophagy was both necessary and sufficient to extend lifespan on ad lib diet and also prevented further iTRF-mediated lifespan extension. In contrast, day-specific induction of autophagy did not extend lifespan. Thus, these results identify “night-specific” circadian-regulated autophagy as a critical contributor to iTRF-mediated health benefits in Drosophila. As both circadian regulation and autophagy are highly conserved processes that play roles in mammalian aging, this work highlights the possibility that behavioral or pharmaceutical interventions stimulating circadian-regulated autophagy may provide people with similar health benefits such as delays in aging pathology and lifespan extension.

Circadian autophagy drives longevity response to Intermittent Time-Restricted-Feeding (iTRF)