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昼夜自噬驱动iTRF介导的长寿
作者:小柯机器人 发布时间:2021/10/9 13:55:19

美国哥伦比亚大学Mimi Shirasu-Hiza团队发现昼夜自噬驱动iTRF介导的长寿。2021年9月29日,《自然》杂志在线发表了这项成果。

为了利用果蝇的遗传工具和特征明显的衰老标志物,研究人员开发了一种间歇性时间限制性喂养(iTRF)饮食方案,该方案能有力地延长果蝇的寿命并延迟肌肉和肠道中衰老标志物的出现。研究人员发现,iTRF增强了昼夜调节的转录,iTRF介导的寿命延长需要昼夜调节和自噬,这是一条保守的长寿途径。夜间特异性诱导自噬对延长自由饮食的寿命是必要的,也是充分的,同时也能阻止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调节的自噬是iTRF介导的果蝇健康益处的一个重要贡献因素。

由于昼夜节律调节和自噬在人类衰老中是高度保守的过程,这项工作突出表明,刺激昼夜节律调节的自噬的行为或药物干预可能为人们提供类似的健康益处,如延迟衰老和延长寿命。

据了解,时间限制性喂养(TRF)作为一种潜在的抗衰老治疗方法,最近在从果蝇到人类的生物体中获得了关注。TRF将食物摄入限制在一天中的特定时段。由于TRF控制进食的时间,而不是营养或热量的含量,TRF被推测为依赖于昼夜节律的调节功能,其影响的潜在分子机制仍不清楚。

附:英文原文

Title: Circadian autophagy drives iTRF-mediated longevity

Author: 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

Issue&Volume: 2021-09-29

Abstract: Time-restricted feeding (TRF) has recently gained interest as a potential anti-ageing treatment for organisms from Drosophila to humans1,2,3,4,5. 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.

DOI: 10.1038/s41586-021-03934-0

Source: https://www.nature.com/articles/s41586-021-03934-0

期刊信息

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html