Plasma membrane damage limits replicative lifespan in yeast and induces premature senescence in human fibroblasts.

ABSTRACT: Plasma membrane damage (PMD) occurs in all cell types due to environmental perturbation and cell-autonomous activities. However, cellular outcomes of PMD remain largely unknown except for recovery or death. In this study, using budding yeast and normal human fibroblasts, we found that cellular senescence-stable cell cycle arrest contributing to organismal aging-is the long-term outcome of PMD. Our genetic screening using budding yeast unexpectedly identified a close genetic association between PMD response and replicative lifespan regulations. Furthermore, PMD limits replicative lifespan in budding yeast; upregulation of membrane repair factors ESCRT-III (SNF7) and AAA-ATPase (VPS4) extends it. In normal human fibroblasts, PMD induces premature senescence via the Ca²⁺-p53 axis b

SUBMITTER: Suda K 

PROVIDER: S-EPMC10950784 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature