Circadian autophagy drives iTRF-mediated longevity

昼夜节律 自噬 长寿 生物 老化 生物钟 细胞生物学 内分泌学 遗传学 细胞凋亡
作者
Matt Ulgherait,Adil M. Midoun,Scarlet J. Park,Jared A. Gatto,Samantha J. Tener,Julia Siewert,Naomi Klickstein,Julie C. Canman,William W. Ja,Mimi Shirasu‐Hiza
出处
期刊:Nature [Springer Nature]
卷期号:598 (7880): 353-358 被引量:114
标识
DOI:10.1038/s41586-021-03934-0
摘要

Time-restricted feeding (TRF) has recently gained interest as a potential anti-ageing treatment for organisms from Drosophila to humans1-5. TRF restricts food intake to specific hours of the day. Because TRF controls the timing of feeding, rather than nutrient or caloric content, TRF has been hypothesized to depend on circadian-regulated functions; the underlying molecular mechanisms of its effects remain unclear. Here, to exploit the genetic tools and well-characterized ageing markers of Drosophila, we developed an intermittent TRF (iTRF) dietary regimen that robustly extended fly lifespan and delayed the onset of ageing markers in the muscles and gut. We found that iTRF enhanced circadian-regulated transcription and that iTRF-mediated lifespan extension required both circadian regulation and autophagy, a conserved longevity pathway. Night-specific induction of autophagy was both necessary and sufficient to extend lifespan on an ad libitum diet and also prevented further iTRF-mediated lifespan extension. By contrast, day-specific induction of autophagy did not extend lifespan. Thus, these results identify circadian-regulated autophagy as a critical contributor to iTRF-mediated health benefits in Drosophila. Because both circadian regulation and autophagy are highly conserved processes in human ageing, this work highlights the possibility that behavioural or pharmaceutical interventions that stimulate circadian-regulated autophagy might provide people with similar health benefits, such as delayed ageing and lifespan extension.
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