Plasma membrane damage limits replicative lifespan in yeast and induces premature senescence in human fibroblasts.
Nat Aging
; 4(3): 319-335, 2024 Mar.
Article
em En
| MEDLINE
| ID: mdl-38388781
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 but not the major senescence pathway, DNA damage response pathway. Transient upregulation of ESCRT-III (CHMP4B) suppressed PMD-dependent senescence. Together with mRNA sequencing results, our study highlights an underappreciated but ubiquitous senescent cell subtype PMD-dependent senescent cells.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Limite:
Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article