title: Mitoflash frequency in early adulthood predicts lifespan in Caenorhabditis elegans.
abstract: 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.
authors: 1] College of Biological Sciences, China Agricultural University, Beijing 100094, China [2] National Institute of Biological Sciences, Beijing, Beijing 102206, China [3].
authors: En-Zhi
authors: EZ
authors: Shen
authors: 1] College of Biological Sciences, China Agricultural University, Beijing 100094, China [2] National Institute of Biological Sciences, Beijing, Beijing 102206, China [3].
authors: Chun-Qing
authors: CQ
authors: Song
authors: 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].
authors: Yuan
authors: Y
authors: Lin
authors: National Institute of Biological Sciences, Beijing, Beijing 102206, China.
authors: Wen-Hong
authors: WH
authors: Zhang
authors: Department of Statistics, National Cheng Kung University, Tainan 70101, Taiwan.
authors: Pei-Fang
authors: PF
authors: Su
authors: National Institute of Biological Sciences, Beijing, Beijing 102206, China.
authors: Wen-Yuan
authors: WY
authors: Liu
authors: National Institute of Biological Sciences, Beijing, Beijing 102206, China.
authors: Pan
authors: P
authors: Zhang
authors: 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.
authors: Jiejia
authors: J
authors: Xu
authors: 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.
authors: Na
authors: N
authors: Lin
authors: National Institute of Biological Sciences, Beijing, Beijing 102206, China.
authors: Cheng
authors: C
authors: Zhan
authors: 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.
authors: Xianhua
authors: X
authors: Wang
authors: Vanderbilt Centre for Quantitative Sciences, Vanderbilt University, Nashville, Tennessee 37232, USA.
authors: Yu
authors: Y
authors: Shyr
authors: 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.
authors: Heping
authors: H
authors: Cheng
authors: National Institute of Biological Sciences, Beijing, Beijing 102206, China.
authors: Meng-Qiu
authors: MQ
authors: Dong
mesh_terms: D000375:Aging / Q000378:metabolism; D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000166:cytology / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D029742:Caenorhabditis elegans Proteins / Q000235:genetics; D003643:Death; D004734:Energy Metabolism; D004777:Environment; D006038:Glyoxylates / Q000378:metabolism; D057850:Hermaphroditic Organisms; D008136:Longevity / Q000235:genetics / Q000502:physiology; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D008954:Models, Biological; D009132:Muscles / Q000166:cytology; D009154:Mutation; D018384:Oxidative Stress; D011972:Receptor, Insulin / Q000235:genetics; D012098:Reproduction; D013269:Stochastic Processes; D013481:Superoxides / Q000032:analysis / Q000378:metabolism*; D013997:Time Factors
chemical_list: D029742:Caenorhabditis elegans Proteins; D006038:Glyoxylates; D013481:Superoxides; C107483:DAF-2 protein, C elegans; D011972:Receptor, Insulin; C031150:glyoxylic acid