Calorie restriction (CR) is the most robust longevity intervention, extending lifespan from yeast to mammals. Numerous conserved pathways regulating aging and mediating CR have been identified; however, the overall proteomic changes during these conditions remain largely unexplored. We compared proteomes between young and replicatively aged yeast cells under normal and CR conditions using the Stable-Isotope Labeling by Amino acids in Cell culture (SILAC) quantitative proteomics and discovered distinct signatures in the aging proteome. We found remarkable proteomic similarities between aged and CR cells, including induction of stress response pathways, providing evidence that CR pathways are engaged in aged cells. These observations also uncovered aberrant changes in mitochondria membrane proteins as well as a proteolytic cellular state in old cells. These proteomics analyses help identify potential genes and pathways that have causal effects on longevity.

卡路里限制 (CR) 是最有效的长寿干预措施，可以延长从酵母到哺乳动物的寿命。已经确定了许多调节衰老和介导 CR 的保守途径；然而，在这些条件下的整体蛋白质组学变化在很大程度上仍未被探索。我们使用细胞培养中氨基酸的稳定同位素标记 (SILAC) 定量蛋白质组学比较了正常和 CR 条件下年轻和复制性老化酵母细胞之间的蛋白质组，并发现老化蛋白质组中的不同特征。我们发现衰老细胞和 CR 细胞之间存在显着的蛋白质组学相似性，包括诱导应激反应途径，这提供了 CR 途径参与衰老细胞的证据。这些观察还揭示了线粒体膜蛋白的异常变化以及旧细胞中的蛋白水解细胞状态。这些蛋白质组学分析有助于识别对长寿有因果影响的潜在基因和途径。