1] College of Biological Sciences, China Agricultural University, Beijing 100094, China [2] National Institute of Biological Sciences, Beijing, Beijing 102206, China [3].
1] State Key Laboratory of Biomembrane and Membrane Biotechnology, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China [2].
Nature. 2014 Apr 3;508(7494):128-32. doi: 10.1038/nature13012. Epub 2014 Feb 12.
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.
几十年来，人们一直认为线粒体是衰老的生物钟，但证据并不完整。在这里，我们通过体内可视化线粒体闪烁（mitoflash）显示线粒体功能与衰老之间存在很强的耦合，mitoflash 是一种频率编码的光学读出信号，反映了单个线粒体水平的自由基产生和能量代谢。秀丽隐杆线虫咽肌中的 mitoflash 活性在生殖活跃的成虫第 3 天和动物开始死亡的第 9 天达到峰值。大量的遗传突变和环境因素反过来修饰了寿命和第 3 天的 mitoflash 频率。即使在同基因群体中，第 3 天的 mitoflash 频率也与个体动物的寿命呈负相关。此外，乙醛酸循环的活性增强导致第 3 天 mitoflash 频率降低和 daf-2 突变体动物寿命延长。这些结果表明，第 3 天的 mitoflash 频率是秀丽隐杆线虫寿命的一个强大预测因子，跨越了遗传、环境和随机因素。它们还支持这样一种观点，即衰老的速度虽然可以在以后的生活中进行调整，但在生殖停止之前已经在相当程度上确定了。
