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Mitoflash frequency in early adulthood predicts lifespan in Caenorhabditis elegans
En-Zhi Shen, Chun-Qing Song, Yuan Lin, Wen-Hong Zhang, Pei-Fang Su, Wen-Yuan Liu, Pan Zhang, Jiejia Xu, Na Lin, Cheng Zhan, Xianhua Wang, Yu Shyr, Heping Cheng & Meng-Qiu Dong
It has been theorized for decades that mitochondria act as the biological clock of ageing1, 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 level2, 3. 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.