| RRC ID |
82120
|
| Author |
Suda K, Moriyama Y, Razali N, Chiu Y, Masukagami Y, Nishimura K, Barbee H, Takase H, Sugiyama S, Yamazaki Y, Sato Y, Higashiyama T, Johmura Y, Nakanishi M, Kono K.
|
| Title |
Plasma membrane damage limits replicative lifespan in yeast and induces premature senescence in human fibroblasts.
|
| Journal |
Nat Aging
|
| 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.
|
| Volume |
4(3)
|
| Pages |
319-335
|
| Published |
2024-3-1
|
| DOI |
10.1038/s43587-024-00575-6
|
| PII |
10.1038/s43587-024-00575-6
|
| PMID |
38388781
|
| PMC |
PMC10950784
|
| MeSH |
Adenosine Triphosphatases / metabolism
Cell Membrane / metabolism
Cellular Senescence / genetics
Endosomal Sorting Complexes Required for Transport / genetics
Fibroblasts
Humans
Longevity
Saccharomyces cerevisiae* / genetics
Saccharomyces cerevisiae Proteins* / metabolism
Tumor Suppressor Protein p53 / genetics
|
| Resource |
| Human and Animal Cells |
HeLa(RCB0007)
WI-38(RCB0702) |
