Analysis of long-lived C. elegans daf-2 mutants using serial analysis of gene expression
Analysis of long-lived C. elegans daf-2 mutants using serial analysis of gene expression
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DOI：
10.1101/gr.3274805
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发表时间：
2005-05-01
期刊：
影响因子：
7
通讯作者：
Riddle, DL
中科院分区：
文献类型：
--
作者：
Halaschek-Wiener, J;Khattra, JS;Riddle, DL
我们已经使用基因表达序列分析(SAGE)在一个长寿的秀丽线虫daf-2(胰岛素/LGF受体)突变体中鉴定了与长寿相关的基因，这是一种通过对短标签进行测序来有效量化大量mRNA转录本的方法。这些突变的蠕虫中daf-2信号的减少导致平均寿命翻了一番。我们从1、6和10d龄的成虫daf-2以及1和6d龄的对照成虫制备了线虫鼠尾草文库。代表不同年龄的daf-2文库之间以及daf-2与对照文库之间的基因表达差异不仅鉴定了单个基因，而且鉴定了差异调控的整个基因微弱。这些基因家族是主要代谢途径的一部分，包括脂肪、蛋白质和能量代谢、应激反应和细胞结构。亲缘关系密切的家庭成员的相似表达模式强调了这些基因在衰老相关过程中的重要性。对代谢相关基因的全球分析显示，DAF-2中年突变体的低代谢特征随着年龄的增加而减弱。将我们的结果与最近的微阵列研究进行比较，突出了一组重叠的基因，这些基因在整个进化过程中高度保守，因此代表了控制衰老和长寿的强有力的候选基因。
We have identified longevity-associated genes in a long-lived Caenorhabdids elegans daf-2 (insulin/lGF receptor) mutant using serial analysis of gene expression (SAGE), a method that efficiently quantifies large numbers of mRNA transcripts by sequencing short tags. Reduction of daf-2 signaling in these Mutant worms leads to a doubling in mean lifespan. We prepared C elegans SAGE libraries from 1, 6, and 10-d-old adult daf-2 and from 1 and 6-d-old control adults. Differences in gene expression between daf-2 libraries representing different ages and between daf-2 versus control libraries identified not only single genes, but whole gene fainilies that were differentially regulated. These gene families are part of major metabolic pathways including lipid, protein, and energy metabolism, stress response, and cell structure. Similar expression patterns of closely related family members emphasize the importance of these genes in aging-related processes. Global analysis of metabolism-associated genes showed hypometabolic features in mid-life daf-2 mutants that diminish with advanced age. Comparison Of Our results to recent microarray Studies highlights sets of overlapping genes that are highly conserved throughout evolution and thus represent strong candidate genes that control aging and longevity.