Department of Biology, Virginia Commonwealth University, Richmond, VA, 23284, USA.
Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, 98195, USA.
Geroscience. 2022 Aug;44(4):1995-2006. doi: 10.1007/s11357-022-00604-5. Epub 2022 Jun 13.
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.
在细胞水平上，许多衰老的方面在不同物种中是保守的。这已被许多在简单模式生物如酿酒酵母、秀丽隐杆线虫和黑腹果蝇中的研究证明。由于大多数遗传筛选都是通过反向遗传学检查功能丧失突变或基因表达降低，因此，作为衰老过程的潜在调节剂，必需基因往往被忽视。通过增加一组保守的必需基因的表达水平的方法，我们发现这些基因中有 21%导致酿酒酵母的复制寿命延长。这大于通过缺失发现影响寿命的基因的 3.5%左右，这表明必需基因的激活可能对延长寿命有相对不成比例的影响。我们实验的结果表明，必需基因的过表达是一种丰富的、相对未被探索的增加真核生物寿命的方法。
