Chronological aging in yeast resembles aging in mammalian, postmitotic tissues. Such chronological aging begins with entrance into the stationary phase after the nutrients are exhausted. Many changes in metabolism take place at this moment, and survival in this phase strongly depends on oxidative-stress resistance. In this study, hypo- and hyperglycogenic phenotypes of Saccharomyces cerevisiae strains with deletions of carbohydrate-metabolism enzymes were selected, and a comparison of their chronological longevities was made. Stress sensitivity, ROS, and apoptosis markers during aging were analyzed in the emerged candidates. Among the strains that accumulated greater amounts of glycogen, the deletion of glycogen phosphorylase, gph1delta, was unique in showing a shortened life span, stress intolerance, and higher levels of ROS during its survival. The transcription of superoxide dismutase genes during survival was three- to fourfold lower in gph1delta. Extra copies of SOD1/2 counteracted the stress sensitivity and the accelerated aging of gph1delta. In conclusion, the lack of gph1 produced a rapidly aging strain, which could be attributed, at least in part, to the weakened stress resistance associated with the decreased expression of both SODs. Gph1p seems to be a candidate in a scenario that could link early metabolic changes with other targets of the stress response during stationary-phase survival.

译文

酵母的时间老化类似于哺乳动物有丝分裂后组织的老化。这种按时间顺序排列的衰老始于营养物质耗尽后进入固定相。此时发生了许多代谢变化,并且在此阶段的生存在很大程度上取决于抗氧化应激的抗性。在这项研究中,选择了具有碳水化合物代谢酶缺失的酿酒酵母菌株的低糖和高糖表型,并比较了它们的时间长度。在出现的候选者中分析了衰老过程中的应激敏感性,ROS和凋亡标志物。在积累大量糖原的菌株中,糖原磷酸化酶gph1delta的缺失是独特的,其寿命缩短,应激不耐受和生存期间ROS水平较高。在gph1delta中,存活期间超氧化物歧化酶基因的转录降低了三到四倍。额外的SOD1/2副本抵消了gph1delta的应力敏感性和加速老化。总之,缺乏gph1会产生快速老化的菌株,这至少部分归因于与两种sod表达降低相关的抗逆性减弱。在可以将早期代谢变化与静止期生存期间的应激反应的其他目标联系起来的情况下,Gph1p似乎是候选者。

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