Seroude Laurent, Brummel Ted, Kapahi Pankaj, Benzer Seymour
California Institute of Technology, Division of Biology 156-29, Pasadena, CA 91125, USA.
Aging Cell. 2002 Oct;1(1):47-56. doi: 10.1046/j.1474-9728.2002.00007.x.
The relationship between gene expression and the regulation of longevity is poorly understood. Previous studies focusing on microarray or tissue-specific changes in gene expression as a function of age have provided evidence that gene expression is a dynamic process which is regulated, even late in an organism's lifespan. Using the enhancer-trap technique, a systematic analysis of the spatio-temporal regulation of gene expression in tissues of adult Drosophila is presented. As many as 80% of enhancer traps analysed displayed (some form of) transcriptional change with age. In some cases the rate of change in expression was found to correlate with changes in longevity under various conditions, suggesting that they may be indicators of 'physiological age' and therefore valuable markers for dissecting the aging process. Molecular analysis of enhancer traps that showed increased activity with age was performed to identify candidate genes that may be important in the regulation of longevity; we identified changes in reporters associated with immunity, microtubule organization and muscle function.
基因表达与寿命调节之间的关系目前还知之甚少。先前聚焦于基因表达随年龄变化的微阵列或组织特异性变化的研究表明,基因表达是一个动态过程,即使在生物体寿命后期也受到调控。本文利用增强子捕获技术,对成年果蝇组织中基因表达的时空调节进行了系统分析。在分析的增强子捕获中,多达80%表现出(某种形式的)随年龄的转录变化。在某些情况下,发现表达变化率与不同条件下的寿命变化相关,这表明它们可能是“生理年龄”的指标,因此是剖析衰老过程的有价值标记。对随年龄活性增加的增强子捕获进行了分子分析,以鉴定可能在寿命调节中起重要作用的候选基因;我们发现与免疫、微管组织和肌肉功能相关的报告基因发生了变化。