Manière X, Krisko A, Pellay F X, Di Meglio J-M, Hersen P, Matic I
Inserm Unit 1001, Université Paris-Descartes, Sorbonne Paris Cité, Faculté de Médecine Paris Descartes, 75014 Paris, France.
Inserm Unit 1001, Université Paris-Descartes, Sorbonne Paris Cité, Faculté de Médecine Paris Descartes, 75014 Paris, France; Mediterranean Institute for Life Sciences (MedILS), 21000 Split, Croatia.
Exp Gerontol. 2014 Dec;60:12-7. doi: 10.1016/j.exger.2014.09.005. Epub 2014 Sep 16.
Individual lifespans of isogenic organisms, such as Caenorhabditis elegans nematodes, fruit flies, and mice, vary greatly even under identical environmental conditions. To study the molecular mechanisms responsible for such variability, we used an assay based on the measurement of post-reproductive nematode movements stimulated by a moderate electric field. This assay allows for the separation of individual nematodes based on their speed. We show that this phenotype could be used as a biomarker for aging because it is a better predictor of lifespan than chronological age. Fast nematodes have longer lifespans, fewer protein carbonyls, higher heat-shock resistance, and higher transcript levels of the daf-16 and hsf-1 genes, which code for the stress response transcription factors, than slow nematodes. High transcript levels of the genes coding for heat-shock proteins observed in slow nematodes correlate with lower heat-shock resistance, more protein carbonyls, and shorter lifespan. Taken together, our data suggests that shorter lifespan results from early-life damage accumulation that causes subsequent faster age-related deterioration.
同基因生物(如秀丽隐杆线虫、果蝇和小鼠)的个体寿命即使在相同环境条件下也存在很大差异。为了研究造成这种差异的分子机制,我们采用了一种基于测量适度电场刺激下生殖后期线虫运动的测定方法。该测定方法能够根据线虫的速度对个体线虫进行分离。我们表明,这种表型可用作衰老的生物标志物,因为与实际年龄相比,它是寿命的更好预测指标。快速移动的线虫比慢速移动的线虫寿命更长、蛋白质羰基含量更少、热休克抗性更高,并且编码应激反应转录因子的daf-16和hsf-1基因的转录水平更高。在慢速移动的线虫中观察到的热休克蛋白编码基因的高转录水平与较低的热休克抗性、更多的蛋白质羰基以及更短的寿命相关。综上所述,我们的数据表明,较短的寿命是由生命早期的损伤积累导致随后与年龄相关的更快衰退所致。