Science：“饥饿感”如何让果蝇不用少吃也能长寿？
- ①限制膳食支链氨基酸（BCAA）尤其异亮氨酸，或激活促进饥饿感/进食动机的特定神经，能诱导果蝇的饥饿状态，使其在进食量增加的情况下延长寿命；
- ②BCAA限制可改变果蝇神经的组蛋白修饰模式，在分子层面上编码饥饿感，但饥饿似乎通过不同的神经途径调节进食和衰老；
- ③组蛋白乙酰化组的变化介导了BCAA限制引起的进食增加，并部分介导其延寿作用；
- ④此外，BCAA限制通过增加组蛋白变体H3.3促进短期进食，而长期饥饿似乎可改变食欲调控设定点，从而延缓衰老。
主编推荐语
热量限制在一些实验动物中有延长寿命的作用。Science最新发表的一项研究表明，饥饿能增加果蝇的寿命。通过限制果蝇的支链氨基酸摄入，或通过光遗传学刺激与进食动机相关的大脑神经元，可诱导果蝇的饥饿感，在促进果蝇进食的同时，延长了它们的寿命。饥饿的这种作用与大脑中特定神经元的组蛋白的变化有关，且其对进食和衰老的调控似乎是通过不同的神经通路实现的。
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Effects of hunger on neuronal histone modifications slow aging in Drosophila
饥饿对神经元组蛋白修饰的影响减缓了果蝇的衰老速度
10.1126/science.ade1662
05-11, Article
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Hunger is an ancient drive, yet the molecular nature of pressures of this sort and how they modulate physiology are unknown. We find that hunger modulates aging in Drosophila. Limitation of branched-chain amino acids (BCAAs) or activation of hunger-promoting neurons induced a hunger state that extended life span despite increased feeding. Alteration of the neuronal histone acetylome was associated with BCAA limitation, and preventing these alterations abrogated the effect of BCAA limitation to increase feeding and extend life span. Hunger acutely increased feeding through usage of the histone variant H3.3, whereas prolonged hunger seemed to decrease a hunger set point, resulting in beneficial consequences for aging. Demonstration of the sufficiency of hunger to extend life span reveals that motivational states alone can be deterministic drivers of aging.
First Authors:
K J Weaver
Correspondence Authors:
K J Weaver,S D Pletcher
All Authors:
K J Weaver,R A Holt,E Henry,Y Lyu,S D Pletcher
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