Time-restricted feeding (TRF) has recently gained interest as a potential anti-ageing treatment for organisms from Drosophila to humans^1,2,3,4,5. 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.

限时喂养 (TRF) 最近作为一种潜在的抗衰老治疗方法引起了人们的兴趣，它适用于从果蝇到人类的生物体^1,2,3,4,5 。 TRF 将食物摄入量限制在一天中的特定时段。由于 TRF 控制进食时间，而不是营养或热量含量，因此推测 TRF 取决于昼夜节律调节功能；其影响的潜在分子机制仍不清楚。在这里，为了利用果蝇的遗传工具和充分表征的衰老标志物，我们开发了一种间歇性 TRF (iTRF) 饮食方案，可以有效延长果蝇的寿命并延缓肌肉和肠道衰老标志物的出现。我们发现 iTRF 增强了昼夜节律调节的转录，并且 iTRF 介导的寿命延长需要昼夜节律调节和自噬（一种保守的长寿途径）。夜间特异性诱导自噬对于延长随意饮食的寿命来说是必要且充分的，并且还可以防止 iTRF 介导的寿命进一步延长。相比之下，特定日期诱导自噬并不能延长寿命。因此，这些结果表明昼夜节律调节的自噬是 iTRF 介导的果蝇健康益处的关键贡献者。由于昼夜节律调节和自噬都是人类衰老过程中高度保守的过程，因此这项工作强调了刺激昼夜节律调节自噬的行为或药物干预可能为人们提供类似的健康益处的可能性，例如延缓衰老和延长寿命。