Ruzanov Peter, Riddle Donald L, Marra Marco A, McKay Sheldon J, Jones Steven M
Genome Sciences Centre, BC Cancer Research Centre, 570 West 7th Avenue, Vancouver, BC, Canada.
Exp Gerontol. 2007 Aug;42(8):825-39. doi: 10.1016/j.exger.2007.04.002. Epub 2007 Apr 21.
We used Serial Analysis of Gene Expression (SAGE) to compare the global transcription profiles of long-lived mutant daf-2 adults and dauer larvae, aiming to identify aging-related genes based on similarity of expression patterns. Genes that are expressed similarly in both long-lived types potentially define a common life-extending program. Comparison of eight SAGE libraries yielded a set of 120 genes, the expression of which was significantly different in long-lived worms vs. normal adults. The gene annotations indicate a strong link between oxidative stress and life span, further supporting the hypothesis that metabolic activity is a major determinant in longevity. The SAGE data show changes in mRNA levels for electron transport chain components, elevated expression of glyoxylate shunt enzymes and significantly reduced expression for components of the TCA cycle in longer-lived nematodes. We propose a model for enhanced longevity through a cytochrome c oxidase-mediated reduction in reactive oxygen species commonly held to be a major contributor to aging.
我们使用基因表达序列分析(SAGE)来比较长寿突变体daf-2成虫和 dauer 幼虫的整体转录谱,旨在基于表达模式的相似性鉴定与衰老相关的基因。在两种长寿类型中表达相似的基因可能定义了一个共同的寿命延长程序。对八个 SAGE 文库的比较产生了一组 120 个基因,其在长寿蠕虫与正常成虫中的表达存在显著差异。基因注释表明氧化应激与寿命之间存在紧密联系,进一步支持了代谢活动是寿命的主要决定因素这一假说。SAGE 数据显示,在寿命更长的线虫中,电子传递链成分的 mRNA 水平发生变化,乙醛酸循环酶的表达升高,而三羧酸循环成分的表达显著降低。我们提出了一个通过细胞色素 c 氧化酶介导的活性氧减少来延长寿命的模型,活性氧通常被认为是衰老的主要促成因素。