Mitoflash frequency in early adulthood predicts lifespan in Caenorhabditis elegans

• Published in: Nature (London) Vol. 508; no. 7494; pp. 128 - 132
• Main Authors: Shen, En-Zhi, Song, Chun-Qing, Lin, Yuan, Zhang, Wen-Hong, Su, Pei-Fang, Liu, Wen-Yuan, Zhang, Pan, Xu, Jiejia, Lin, Na, Zhan, Cheng, Wang, Xianhua, Shyr, Yu, Cheng, Heping, Dong, Meng-Qiu
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 03.04.2014; Nature Publishing Group
• Subjects: 14; 14/19; 14/35; 631/136/7; 631/208/182; 631/443/7; 631/80/642/333/1465; 64/11; 82/58; 9/10; Age; Aging; Aging - metabolism; Analysis; Animals; Animals, Genetically Modified; Biological clocks; Caenorhabditis elegans; Caenorhabditis elegans - cytology; Caenorhabditis elegans - genetics; Caenorhabditis elegans - metabolism; Caenorhabditis elegans - physiology; Caenorhabditis elegans Proteins - genetics; Death; Energy Metabolism; Environment; Environmental aspects; Environmental factors; Forecasts and trends; Genetic aspects; Glyoxylates - metabolism; Hermaphroditic Organisms; Humanities and Social Sciences; Insulin; letter; Life span; Life spans (Biology); Longevity - genetics; Longevity - physiology; Male; Mitochondria; Mitochondria - metabolism; Mitochondrial biogenesis; Models, Biological; multidisciplinary; Muscles; Muscles - cytology; Mutation; Oxidative Stress; Proteins; Receptor, Insulin - genetics; Reproduction; Science; Stochastic Processes; Superoxides - analysis; Superoxides - metabolism; Testing; Time Factors; China
• ISSN: 0028-0836; 1476-4687; 1476-4687
• DOI: 10.1038/nature13012

In Caenorhabditis elegans , mitochondrial activity as measured by the frequency of the mitochondrial flash in young adult animals is a powerful predictor of lifespan across genetic, environmental and stochastic factors. Mitoflash activity tests ageing theory The mitochondrial theory of ageing, developed more than 40 years ago based on work on the roundworm Caenorhabditis elegans , proposes that the mitochondria are the main drivers of ageing — defined as an increase in the probability of death with increasing chronological age. This study is a direct test of the theory using an approach made possible by the recent demonstration that mitochondria undergo stochastic bursts of superoxide production that can be visualized as mitochondrial flashes. The flash frequency of these 'mitoflashes' is sensitive to oxidative stress and metabolic changes. The authors observe that mitoflash activity in the pharyngeal muscles of a 3-day-old adult C. elegans worm inversely correlates with lifespan of the animal. A large variety of genetic mutations and environmental factors inversely modify the lifespan and the mitoflash frequency at day 3. Even within an isogenic population of worms the day-3 mitoflash frequency negatively correlates with lifespan. Day-3 mitoflash frequency is shown to be a powerful predictor of C. elegans lifespan reflecting a range of genetic and environmental influences, suggesting an intimate connection between mitochondrial function and ageing. It has been theorized for decades that mitochondria act as the biological clock of ageing 1 , 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 2 , 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.