Evidence that conserved essential genes are enriched for pro-longevity factors

At the cellular level, many aspects of aging are conserved across species. This has been demonstrated by numerous studies in simple model organisms like Saccharomyces cerevisiae, Caenorhabdits elegans, and Drosophila melanogaster. Because most genetic screens examine loss of function mutations or decreased expression of genes through reverse genetics, essential genes have often been overlooked as potential modulators of the aging process. By taking the approach of increasing the expression level of a subset of conserved essential genes, we found that 21% of these genes resulted in increased replicative lifespan in S. cerevisiae. This is greater than the ~3.5% of genes found to affect lifespan upon deletion, suggesting that activation of essential genes may have a relatively disproportionate effect on increasing lifespan. The results of our experiments demonstrate that essential gene overexpression is a rich, relatively unexplored means of increasing eukaryotic lifespan.在细胞层面，衰老的诸多特征在不同物种间具有保守性。这一点已在酿酒酵母（Saccharomyces cerevisiae）、秀丽隐杆线虫（Caenorhabditis elegans）以及黑腹果蝇（Drosophila melanogaster）等简单模式生物的大量研究中得到证实。由于大多数遗传筛选通过反向遗传学技术研究基因的功能缺失突变或表达下调，因此必需基因（essential gene）往往被忽视，未被视为衰老过程的潜在调控因子。本研究通过上调一组保守型必需基因的表达水平，发现在酿酒酵母（S. cerevisiae）中，有21%的这类基因可延长其复制寿命。这一比例远高于通过基因敲除发现的影响寿命的基因比例（约3.5%），这表明激活必需基因对延长寿命的作用相对更为显著。本研究的实验结果表明，必需基因过表达是一种丰富且尚未被充分探索的真核生物寿命延长手段。