February 22, 2024Open Access

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

KSKojiro SudaKyoto Institute of Technology YMYohsuke MoriyamaOkinawa Institute of Science and Technology Graduate University NRNurhanani RazaliOkinawa Institute of Science and Technology Graduate University

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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 Ca

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