Mitoflash frequency in early adulthood predicts lifespan in Caenorhabditis elegans

摘要

It has been theorized for decades that mitochondria act as the biological clock of ageing, but the evidence is incomplete. Here we show a strong coupling between mitochondrial function and ageing by in vivo visualization of the mitochondrial flash (mitoflash), a frequency-coded optical readout reflecting free-radical production and energy metabolism at the single-mitochondrion level. Mitoflash activity in Caenorhabditis elegans pharyngeal muscles peaked on adult day 3 during active reproduction and on day 9 when animals started to die off. A plethora of genetic mutations and environmental factors inversely modified the lifespan and the day-3 mitoflash frequency. Even within an isogenic population, the day-3 mitoflash frequency was negatively correlated with the lifespan of individual animals. Furthermore, enhanced activity of the glyoxylate cycle contributed to the decreased day-3 mitoflash frequency and the longevity of daf-2 mutant animals. These results demonstrate that the day-3 mitoflash frequency is a powerful predictor of C. elegans lifespan across genetic, environmental and stochastic factors. They also support the notion that the rate of ageing, although adjustable in later life, has been set to a considerable degree before reproduction ceases.%关于衰老的线粒体理论(40多年前根据通过线虫所做的研究工作建立）认为，线粒体是衰老 (定义为死亡概率随年龄增长的增加）的主要驱动因素。这项研究是对该理论的一个直接验证，它所采用的方法因下面的最新发现而成为可能：线粒体会发生"超氧化物"之生成的随机高峰，这种高峰能够以"线粒体闪烁"的形式被观测到。这种"线粒体闪烁"的频率对氧化应激和代谢变化是敏感的。作者观察到，一条3天大的成年线虫的咽肌中的"线粒体闪烁" 活动与该动物的寿命负相关。大量基因突变和环境因素在出生后第3天反向改变寿命和"线粒体闪烁"频率。即便是在一群同基因的线虫内，第3天的"线粒体闪烁"频率也与寿命负相关。第3天的"线粒体闪烁"频率被发现是线虫寿命的一个强大预测指标，它反映了一系列基因和环境影响，这也说明在线粒体功能与衰老之间存在密切联系。