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Circadian autophagy drives iTRF-mediated longevity

机译：昼夜自噬驾驶ITRF介导的长寿

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Time-restricted feeding (TRF) has recently gained interest as a potential anti-ageing treatment for organisms from Drosophila to humans(1-5). 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.
机译：最近被限制的喂养（TRF）最近获得了来自果蝇对人类的生物的潜在抗衰老治疗（1-5）的潜在抗衰老治疗。 TRF将食物摄入到一天中的特定时间。因为TRF控制喂养的时间，而不是营养或热量含量，但TRF已经假设以取决于昼夜规则的功能;其效果的潜在分子机制仍然不清楚。在这里，为了利用遗传工具和果蝇的良好表征性衰老标志物，我们开发了一个间歇性的TRF（ITRF）饮食方案，鲁棒地延伸了蝇寿命，并延迟了肌肉和肠道中的老化标记的发作。我们发现ITRF增强了昼夜调节的转录，并且ITRF介导的寿命延伸需要昼夜调节和自噬，是一个守恒的长寿途径。夜间诱导自噬均为必要且足以延长AD Libitum饮食的寿命，并且还可以预防进一步的ITRF介导的寿命延伸。相比之下，自噬的特异性诱导没有延长寿命。因此，这些结果将昼夜调节的自噬识别为果蝇介导的ITRF介导的健康益处的关键贡献者。由于昼夜调节和自噬在于人类衰老的高度保守的过程，这项工作突出了刺激昼夜调节的自噬的行为或制药干预的可能性可以为人们提供具有类似的健康益处的人，例如延迟老化和寿命延期。

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  • 来源
    《Nature》 |2021年第7880期|353-358|共6页
  • 作者

    Ulgherait Matt; Midoun Adil M.; Park Scarlet J.; Gatto Jared A.; Tener Samantha J.; Siewert Julia; Klickstein Naomi; Canman Julie C.; Ja William W.; Shirasu-Hiza Mimi;

  • 作者单位

    Columbia Univ Dept Genet & Dev Vagelos Coll Phys & Surg New York NY 10032 USA;

    PSL Res Univ Dept Biol Ecole Normale Super Paris France;

    Scripps Res Inst Skaggs Grad Sch Jupiter FL USA|Scripps Res Inst Dept Neurosci Jupiter FL USA;

    Columbia Univ Dept Genet & Dev Vagelos Coll Phys & Surg New York NY 10032 USA;

    Columbia Univ Dept Genet & Dev Vagelos Coll Phys & Surg New York NY 10032 USA;

    Columbia Univ Dept Genet & Dev Vagelos Coll Phys & Surg New York NY 10032 USA;

    Columbia Univ Dept Biol Sci New York NY 10027 USA;

    Columbia Univ Dept Pathol & Cell Biol Vagelos Coll Phys & Surg New York NY USA;

    Scripps Res Inst Skaggs Grad Sch Jupiter FL USA|Scripps Res Inst Dept Neurosci Jupiter FL USA;

    Columbia Univ Dept Genet & Dev Vagelos Coll Phys & Surg New York NY 10032 USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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