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-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.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10950784 | PMC |
| http://dx.doi.org/10.1038/s43587-024-00575-6 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Mitochondria and the Repurposing of Diabetes Drugs for Off-Label Health Benefits.
Int J Mol Sci
January 2025
Department of Microbiology & Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore.
This review describes our current understanding of the role of the mitochondria in the repurposing of the anti-diabetes drugs metformin, gliclazide, GLP-1 receptor agonists, and SGLT2 inhibitors for additional clinical benefits regarding unhealthy aging, long COVID, mental neurogenerative disorders, and obesity. Metformin, the most prominent of these diabetes drugs, has been called the "Drug of Miracles and Wonders," as clinical trials have found it to be beneficial for human patients suffering from these maladies. To promote viral replication in all infected human cells, SARS-CoV-2 stimulates the infected liver cells to produce glucose and to export it into the blood stream, which can cause diabetes in long COVID patients, and metformin, which reduces the levels of glucose in the blood, was shown to cut the incidence rate of long COVID in half for all patients recovering from SARS-CoV-2.
View Article and Find Full Text PDFTungsten Carbide/Tungsten Oxide Catalysts for Efficient Electrocatalytic Hydrogen Evolution.
Molecules
December 2024
Key Laboratory of Applied Surface and Colloid Chemistry, Ministry of Education, School of Chemistry and Chemical Engineering, Shaanxi Normal University, Xi'an 710119, China.
Catalyzing hydrogen evolution reaction (HER) is a key process in high-efficiency proton exchange membrane water electrolysis (PEMWE) devices. To replace the use of Pt-based HER catalyst, tungsten carbide (WC) is one of the most promising non-noble-metal-based catalysts with low cost, replicable catalytic performance, and durability. However, the preparation access to scalable production of WC catalysts is inevitable.
View Article and Find Full Text PDFAnalysis of different strains of the turquoise killifish identify transcriptomic signatures associated with heritable lifespan differences.
J Gerontol A Biol Sci Med Sci
January 2025
BIO@SNS, Scuola Normale Superiore, Piazza dei Cavalieri,7, Pisa, 56126, Italy.
The African turquoise killifish Nothobranchius furzeri represents an emerging short-lived model for aging research. Captive strains of this species are characterized by large differences in lifespan. To identify the gene expression correlates of this lifespan differences, we analyzed a public transcriptomic dataset consisting of four different tissues in addition to embryos.
View Article and Find Full Text PDFBackground: Atypical teratoid rhabdoid tumor (ATRT) is the most common malignant brain tumor in infants, and more than 60% of children with ATRT die from their tumor. ATRT is associated with mutational inactivation/deletion of , a member of the SWI/SNF chromatin remodeling complex, suggesting that epigenetic events play a critical role in tumor development and progression. Moreover, disruption of SWI/SNF allows unopposed activity of epigenetic repressors, which contribute to tumorigenicity.
View Article and Find Full Text PDFSNP rs6543176 is associated with extreme human longevity but increased risk for cancer.
Geroscience
January 2025
Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Boston, MA, 02111, USA.
Using whole-genome sequencing (WGS) might offer insights into rare genetic variants associated with healthy aging and extreme longevity (EL), potentially pointing to useful therapeutic targets. In this study, we conducted a genome-wide association study using WGS data from the Long Life Family Study and identified a novel longevity-associated variant rs6543176 in the SLC9A2 gene. This SNP also showed a significant association with reduced hypertension risk and an increased, though not statistically significant, cancer risk.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!