Zahn Jacob M, Kim Stuart K
Department of Developmental Biology, Stanford University Medical Center, Stanford, CA 94305, USA.
Curr Opin Biotechnol. 2007 Aug;18(4):355-9. doi: 10.1016/j.copbio.2007.07.004. Epub 2007 Aug 2.
Using DNA microarrays to generate transcriptional profiles of the aging process is a powerful tool for identifying biomarkers of aging. In Caenorhabditis elegans, a number of whole-genome profiling studies identified genes that change expression levels with age. High-throughput RNAi screens in worms determined a number of genes that modulate lifespan when silenced. Transcriptional profiling of the fly head identified a molecular pathway, the 'response to light' gene set, that increases expression with age and could be directly related to the tendency for a reduction in light levels to extend fly's lifespan. In mouse, comparing the gene expression profiles of several drugs to the gene expression profile of caloric restriction identified metformin as a drug whose action could potentially mimic caloric restriction in vivo. Finally, genes in the mitochondrial electron transport chain group decrease expression with age in the human, mouse, fly, and worm.
使用DNA微阵列生成衰老过程的转录谱是识别衰老生物标志物的有力工具。在秀丽隐杆线虫中,多项全基因组分析研究确定了随年龄变化表达水平的基因。在蠕虫中进行的高通量RNA干扰筛选确定了一些基因,这些基因沉默时会调节寿命。果蝇头部的转录谱分析确定了一条分子途径,即“对光的反应”基因集,其表达随年龄增加,可能与光照水平降低延长果蝇寿命的趋势直接相关。在小鼠中,将几种药物的基因表达谱与热量限制的基因表达谱进行比较,确定二甲双胍是一种其作用可能在体内模拟热量限制的药物。最后,线粒体电子传递链组中的基因在人类、小鼠、果蝇和蠕虫中随年龄降低表达。