Department of Biological Sciences, Rensselaer Polytechnic Institute, Troy, NY, USA.
Department of Biological Sciences, Rensselaer Polytechnic Institute, Troy, NY, USA; Wadsworth Center, New York State Department of Health, Albany, NY, USA.
Exp Gerontol. 2018 Jul 15;108:189-200. doi: 10.1016/j.exger.2018.04.020. Epub 2018 Apr 26.
A variety of mild stresses have been shown to extend lifespan in diverse species through hormesis, which is a beneficial response to a stress or toxin that would cause a negative response at a higher exposure. Whether particular stresses induce hormesis can vary with genotype for a given species, and the underlying mechanisms of lifespan extension are only partly understood in most cases. We show that low doses of the DNA damaging or replication stress agents hydroxyurea, methyl methanesulfonate, 4-nitroquinoline 1-oxide, or Zeocin (a phleomycin derivative) lengthened chronological lifespan in Saccharomyces cerevisiae if cells were exposed during growth, but not if they were exposed during stationary phase. Treatment with these agents did not change mitochondrial activity, increase resistance to acetic acid, ethanol, or heat stress, and three of four treatments did not increase resistance to hydrogen peroxide. Stationary phase yeast populations consist of both quiescent and nonquiescent cells, and all four treatments increased the proportion of quiescent cells. Several mutant strains with deletions in genes that influence quiescence prevented Zeocin treatment from extending lifespan and from increasing the proportion of quiescent stationary phase cells. These data indicate that mild DNA damage stress can extend lifespan by promoting quiescence in the absence of mitohormesis or improved general stress responses that have been frequently associated with improved longevity in other cases of hormesis. Further study of the underlying mechanism may yield new insights into quiescence regulation that will be relevant to healthy aging.
多种轻度应激已被证明通过激素作用延长了不同物种的寿命，激素作用是指对一种应激或毒素的有益反应，这种应激或毒素在更高暴露水平下会产生负面反应。在给定物种中，特定应激是否会引起激素作用可能因基因型而异，而且在大多数情况下，延长寿命的潜在机制仅部分得到理解。我们表明，如果细胞在生长过程中暴露于低剂量的 DNA 损伤或复制应激剂羟脲、甲基甲磺酸酯、4-硝基喹啉 1-氧化物或 Zeocin（一种博来霉素衍生物），则会延长酿酒酵母的时序寿命，但如果在静止期暴露则不会。这些药物处理不会改变线粒体活性，不会增加对乙酸、乙醇或热应激的抗性，并且四种处理中的三种不会增加对过氧化氢的抗性。静止期酵母群体由休眠和非休眠细胞组成，所有四种处理都增加了休眠细胞的比例。影响休眠的基因缺失的几种突变株阻止了 Zeocin 处理延长寿命和增加静止期休眠细胞比例。这些数据表明，轻度 DNA 损伤应激可以通过促进休眠来延长寿命，而不需要线粒体激素作用或改善一般应激反应，这些反应在其他激素作用情况下与改善长寿经常相关。对潜在机制的进一步研究可能会为休眠调节提供新的见解，这将与健康老龄化相关。
