Nature: 间歇性限时禁食方案,可以让果蝇的寿命和健康寿命都显著延长
时间限制摄食(TRF)作为一种潜在的抗衰老治疗方法，最近引起了人们的兴趣，从果蝇到人类1,2,3,4,5。TRF会将食物摄入量限制在一天的特定时间。由于 TRF 控制着进食的时间，而不是营养或热量的含量，因此 TRF 被假设依赖于昼夜节律调节的功能; 其作用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特征明显的衰老标记，我们开发了一种间歇性的 TRF (iTRF)饮食方案，有力地延长了果蝇的寿命，并延缓了肌肉和肠道衰老标记的开始。我们发现 iTRF 增强了昼夜节律调节的转录，iTRF 介导的寿命延长需要昼夜节律调节和自噬，一个保守的长寿途径。夜间特异性诱导的自噬对于自由饮食延长寿命是必要的，也是足够的，同时也防止了 itrf 介导的寿命进一步延长。相比之下，特定日期诱导的自噬并不能延长寿命。
因此，这些研究结果表明，昼夜节律调节的自噬作用是果蝇体内 itrf 介导的健康益处的关键因素。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，这项工作突显了刺激昼夜节律调节的自噬的行为或药物干预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。
TRF和对照组（Ad lib）方案的对比
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.
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1 文中说的itrf间歇性禁食和日夜间隔的规律。以每天6点有光照为例，48小时为周期，具体操作，第一天中午12点前可以吃，过12点禁食到第二天上午6点，之后可进食，第三天12点前可以进食，12点后禁食第二周期开始。（概括就是隔天午后不食，每两天少吃一顿午饭一顿晚饭） 夏天禁食周期提早1小时，冬天延后1小时。
2 按照那个图例，是日出后六个小时可以吃，然后禁食20小时，然后可以吃。 48小时一周期。 举例：如果日出为上午6点 【单号】上午6点到12点可以吃，从中午12点到第二天8点为禁食时间，禁食20小时。 【双号】上午8点后可进食。 【每两天一𠆤周期，循环进行】
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