Circadian autophagy drives iTRF-mediated longevity

IF 50.5 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES
Nature Pub Date : 2021-09-29 DOI:10.1038/s41586-021-03934-0
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
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引用次数: 77

Abstract

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. Circadian-regulated autophagy contributes to the health benefits of intermittent time-restricted feeding in Drosophila.

Abstract Image

昼夜节律自噬驱动 iTRF 介导的长寿
限时进食(TRF)作为一种潜在的抗衰老疗法,最近在从果蝇到人类的生物体内引起了广泛关注1-5。TRF将食物摄入限制在一天中的特定时段。由于TRF控制的是进食的时间,而不是营养或热量的含量,因此TRF被假定依赖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,我们利用果蝇的遗传工具和表征良好的老化标记物,开发了一种间歇性TRF(iTRF)饮食方案,它能有效延长果蝇的寿命,并推迟肌肉和肠道老化标记物的发生。我们发现,iTRF增强了昼夜节律调控的转录,iTRF介导的寿命延长需要昼夜节律调控和自噬这一保守的 长寿途径。夜间特异性诱导自噬既是必要的,也足以延长自由饮食的寿命,还能防止iTRF介导的寿命进一步延长。相比之下,白天特异性诱导自噬并不能延长寿命。因此,这些结果确定了昼夜节律调节的自噬是iTRF介导的果蝇健康益处的关键因素。由于昼夜节律调节和自噬在人类衰老过程中都是高度保守的过程,这项研究强调了刺激昼夜节律调节自噬的行为或药物干预措施可能会给人类带来类似的健康益处,如延缓衰老和延长寿命。昼夜节律调节的自噬有助于果蝇间歇性限时进食对健康的益处。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Nature
Nature 综合性期刊-综合性期刊
CiteScore
90.00
自引率
1.20%
发文量
3652
审稿时长
3 months
期刊介绍: Nature is a prestigious international journal that publishes peer-reviewed research in various scientific and technological fields. The selection of articles is based on criteria such as originality, importance, interdisciplinary relevance, timeliness, accessibility, elegance, and surprising conclusions. In addition to showcasing significant scientific advances, Nature delivers rapid, authoritative, insightful news, and interpretation of current and upcoming trends impacting science, scientists, and the broader public. The journal serves a dual purpose: firstly, to promptly share noteworthy scientific advances and foster discussions among scientists, and secondly, to ensure the swift dissemination of scientific results globally, emphasizing their significance for knowledge, culture, and daily life.
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