Molecular Biology Institute of Barcelona (IBMB), CSIC, 08028, Barcelona, Catalonia, Spain.
Molecular Biology Institute of Barcelona (IBMB), CSIC, 08028, Barcelona, Catalonia, Spain.
Exp Cell Res. 2020 Sep 15;394(2):112163. doi: 10.1016/j.yexcr.2020.112163. Epub 2020 Jul 5.
Aging is characterized by the progressive decline of physiology at the cell, tissue and organism level, leading to an increased risk of mortality. Proteotoxic stress, mitochondrial dysfunction and genomic instability are considered major universal drivers of cell aging, and accumulating evidence establishes clear biunivocal relationships among these key hallmarks. In this regard, the finite lifespan of the budding yeast, together with the extensive armamentarium of available analytical tools, has made this single cell eukaryote a key model to study aging at molecular and cellular levels. Here we review the current data that link proteostasis to cell cycle progression in the budding yeast, focusing on senescence as an inherent phenotype displayed by aged cells. Recent advances in high-throughput systems to study yeast mother cells while they replicate are providing crucial information on aging-related processes and their temporal interdependencies at a systems level. In our view, the available data point to the existence of multiple feedback mechanisms among the major causal factors of aging, which would converge into the loss of proteostasis as a nodal driver of cell senescence and death.
衰老是指细胞、组织和机体水平上生理功能的逐渐衰退，导致死亡率增加。蛋白毒性应激、线粒体功能障碍和基因组不稳定性被认为是细胞衰老的主要普遍驱动因素，越来越多的证据确立了这些关键特征之间明确的双向关系。在这方面，出芽酵母的有限寿命，以及广泛的可用分析工具，使这种单细胞真核生物成为研究分子和细胞水平衰老的关键模型。在这里，我们回顾了将蛋白质稳定性与出芽酵母细胞周期进程联系起来的最新数据，重点关注衰老作为衰老细胞表现出的固有表型。最近在研究酵母母细胞复制时使用高通量系统的进展，为衰老相关过程及其在系统水平上的时间相关性提供了关键信息。在我们看来，现有数据表明衰老的主要因果因素之间存在多种反馈机制，这些机制将集中在蛋白质稳定性的丧失上，作为细胞衰老和死亡的节点驱动因素。
