SYSBIO Centre for Systems Biology Milano, Università di Milano-Bicocca, Milano, Italy.
Oxid Med Cell Longev. 2013;2013:802870. doi: 10.1155/2013/802870. Epub 2013 Aug 25.
In Saccharomyces cerevisiae, the chronological lifespan (CLS) is defined as the length of time that a population of nondividing cells can survive in stationary phase. In this phase, cells remain metabolically active, albeit at reduced levels, and responsive to environmental signals, thus simulating the postmitotic quiescent state of mammalian cells. Many studies on the main nutrient signaling pathways have uncovered the strong influence of growth conditions, including the composition of culture media, on CLS. In this context, two byproducts of yeast glucose fermentation, ethanol and acetic acid, have been proposed as extrinsic proaging factors. Here, we report that ethanol and acetic acid, at physiological levels released in the exhausted medium, both contribute to chronological aging. Moreover, this combined proaging effect is not due to a toxic environment created by their presence but is mainly mediated by the metabolic pathways required for their utilization as carbon/energy sources. In addition, measurements of key enzymatic activities of the glyoxylate cycle and gluconeogenesis, together with respiration assays performed in extreme calorie restriction, point to a long-term quiescent program favoured by glyoxylate/gluconeogenesis flux contrary to a proaging one based on the oxidative metabolism of ethanol/acetate via TCA and mitochondrial respiration.
在酿酒酵母中，时序寿命（CLS）被定义为非分裂细胞群体在静止期能够存活的时间长度。在这个阶段，细胞仍然保持代谢活性，尽管活性降低，并且对环境信号有反应，从而模拟哺乳动物细胞的有丝分裂后静止状态。对主要营养信号通路的许多研究揭示了生长条件（包括培养基的组成）对 CLS 的强烈影响。在这种情况下，酵母葡萄糖发酵的两种副产物，乙醇和乙酸，被认为是外在的衰老促进因素。在这里，我们报告说，在耗尽的培养基中以生理水平释放的乙醇和乙酸都有助于时序老化。此外，这种联合的衰老促进作用不是由于它们的存在造成的有毒环境，而是主要通过作为碳/能源来源利用它们所需的代谢途径来介导的。此外，糖异生和糖酵解关键酶活性的测量，以及在极端热量限制下进行的呼吸测定，都指向了由乙醛酸/糖异生通量支持的长期静止程序，而不是基于通过 TCA 和线粒体呼吸进行的乙醇/乙酸氧化代谢的衰老促进程序。
