Cellular senescence is an irreversible growth arrest that contributes to development, tumor suppression, and age-related conditions. Senescent cells show active metabolism compared with proliferating cells, but the underlying mechanisms remain unclear. Here we show that the SETD8/PR-Set7 methyltransferase, which catalyzes mono-methylation of histone H4 at lysine 20 (H4K20me1), suppresses nucleolar and mitochondrial activities to prevent cellular senescence. SETD8 protein was selectively downregulated in both oncogene-induced and replicative senescence. Inhibition of SETD8 alone was sufficient to trigger senescence. Under these states, the expression of genes encoding ribosomal proteins (RPs) and ribosomal RNAs as well as the cyclin-dependent kinase (CDK) inhibitor p16 was increased, with a corresponding reduction of H4K20me1 at each locus. As a result, the loss of SETD8 concurrently stimulated nucleolar function and retinoblastoma protein-mediated mitochondrial metabolism. In conclusion, our data demonstrate that SETD8 acts as a barrier to prevent cellular senescence through chromatin-mediated regulation of senescence-associated metabolic remodeling.
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http://dx.doi.org/10.1016/j.celrep.2017.02.021 | DOI Listing |
Mech Ageing Dev
December 2024
Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Institute for Plastic and Reconstructive Surgery, Shanghai, China. Electronic address:
The exact mechanisms and key functional molecules involved in skin ageing remain largely unknown. Studies linking the expression of messenger RNAs (mRNAs) and small noncoding RNAs (sncRNAs) to skin ageing are limited. In this study, we performed RNA sequencing to assess the effects of ageing on the expression of mRNAs and sncRNAs in rat skin.
View Article and Find Full Text PDFCancer Lett
December 2024
Pancreas Center, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, State Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Tianjin Key Laboratory of Digestive Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin, PR China. Electronic address:
Senescent cells are in a stable state of cell cycle arrest, leading to a natural barrier to tumorigenesis. Senescent cells secrete a pool of molecules, including cytokines, chemokines, proteases, and growth factors, termed the senescence-associated secretory phenotype (SASP), paradoxically contributing to pro-tumorigenic processes. However, the mechanism for regulating senescence and SASP in tumor cells remains unclear.
View Article and Find Full Text PDFAlzheimers Res Ther
December 2024
Normandie Univ, UNICAEN, INSERM, U1237, PhIND "Physiopathology and Imaging of Neurological Disorders", NeuroPresage Team, Cyceron, Boulevard Henri Becquerel, BP 5229, 14074, Caen Cedex, France.
Background: Accumulation of critically short telomeres (CST) is implicated in decreased tissular regenerative capacity and increased susceptibility to degenerative diseases such as Alzheimer's disease (AD). Telomere shortening has also been associated with age-related brain changes. However, it remains unclear whether CST accumulation is directly associated with AD markers or instead amplifies age-related effects, potentially increasing susceptibility of developing AD in cognitively healthy older adults.
View Article and Find Full Text PDFJ Transl Med
December 2024
Department of Endodontics, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
Stem cells derived from the apical papilla (SCAPs) play a crucial role in tooth root development and dental pulp regeneration. They are important seed cells for bone/tooth tissue engineering. However, replicative senescence remains an unavoidable issue as in vitro amplification increases.
View Article and Find Full Text PDFCell Death Differ
December 2024
Division of Molecular Carcinogenesis, Oncode Institute, Netherlands Cancer Institute, Amsterdam, CX, The Netherlands.
Cellular senescence is a stress response that cells can employ to resist cell death. Senescent cells rely on anti-apoptotic signaling for their survival, which can be targeted by senolytic agents, like the BCL-XL, BCL-2, BCL-W inhibitor ABT-263. However, the response to ABT-263 of senescent cancer cells ranges from highly sensitive to refractory.
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