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.

衰老的特征是在细胞，组织和生物体水平上生理学的逐渐下降，导致死亡的风险增加。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力，并且越来越多的证据在这些关键特征之间建立了明确的双向联系。在这方面，发芽酵母的有限寿命以及广泛的可用分析工具集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态与发芽酵母中细胞周期进程联系起来的当前数据，重点是衰老，这是衰老细胞显示的固有表型。用于研究酵母母细胞复制的高通量系统的最新进展为系统提供有关衰老相关过程及其时间相互依赖性的重要信息。我们认为，可用数据表明衰老的主要成因中存在多种反馈机制，这些机制将收敛于作为细胞衰老和死亡的节点驱动力的蛋白稳态丧失。