Publication Date:
2014-02-14
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉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 -- England -- Nature. 2014 Apr 3;508(7494):128-32. doi: 10.1038/nature13012. Epub 2014 Feb 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉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]. ; National Institute of Biological Sciences, Beijing, Beijing 102206, China. ; Department of Statistics, National Cheng Kung University, Tainan 70101, Taiwan. ; 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. ; Vanderbilt Centre for Quantitative Sciences, Vanderbilt University, Nashville, Tennessee 37232, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24522532" target="_blank"〉PubMed〈/a〉
Keywords:
Aging/metabolism
;
Animals
;
Animals, Genetically Modified
;
Caenorhabditis elegans/cytology/genetics/*metabolism/physiology
;
Caenorhabditis elegans Proteins/genetics
;
Death
;
Energy Metabolism
;
Environment
;
Glyoxylates/metabolism
;
Hermaphroditic Organisms
;
*Longevity/genetics/physiology
;
Male
;
Mitochondria/*metabolism
;
Models, Biological
;
Muscles/cytology
;
Mutation
;
Oxidative Stress
;
Receptor, Insulin/genetics
;
Reproduction
;
Stochastic Processes
;
Superoxides/analysis/*metabolism
;
Time Factors
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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