Mechanical damage to the cell membrane was previously believed to trigger two simple cellular outcomes: recovery or death. However, a new study led by the Okinawa Institute of Science and Technology (OIST) reveals mechanical damage can trigger a third outcome, cellular senescence.

The findings are published in Nature Aging in an article titled, “Plasma membrane damage limits replicative lifespan in yeast and induces premature senescence in human fibroblasts.”

“Plasma membrane damage (PMD) occurs in all cell types due to environmental perturbation and cell-autonomous activities,” the researchers wrote. “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.”

Their genetic screening using budding yeast identified a close genetic association between PMD response and replicative lifespan regulations.

“When I started this project, I simply aimed to understand the repair mechanisms of damaged cell membrane,” recalled Keiko Kono, PhD, professor and head of the membranology unit and senior author of this study. “Unexpectedly, we ended up discovering that cell membrane damage, in a sense, switches cell fate.”

“Here we report that PMD limits replicative lifespan in budding yeast and induces stress-dependent premature senescence in normal human fibroblasts,” the researchers noted. “We developed a simple and universal method to induce PMD and designed a systematic genome-wide screen using budding yeast. Based on the screen, we found that PMD limits replicative lifespan in budding yeast and that overexpression of VPS4 and SNF7 extends it.”

Overall, their study highlights an underappreciated subtype of senescent cells and raises new questions to be addressed. Recent studies have shown that senolytic drugs clearing senescent cells ameliorate age-associated disorders. Their study may provide a potential explanation for the in vivo origin of senescent cells and serve as a basis for further studies aimed at developing new therapeutic strategies for PMD-associated diseases.

Previous articleLeaky Blood Vessels in the Brain Linked to Brain Fog in Long COVID Patients
Next articleALS-Linked Protein Could Be Target for Neurodegenerative Disease Therapies