ArticleProceedings of the National Academy of Sciences of the United States of America2012
Sirtuin 6 (SIRT6) rescues the decline of homologous recombination repair during replicative senescence.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
97 citing papers in PubMed, 1 synthesis or guideline pooled it, 176 citations in OpenAlex.
- The Role of c-Abl in Alzheimer's Disease: Guilty or not Guilty?Cellular and molecular neurobiology · 2025Pooled it
- The association of the SIRT6 rs117385980 variant with frailty and longevity: an exploratory study.Scientific reports · 2025Article
- Intermedin Inhibits DNA Damage-Promoted Senescent Phenotype Transition of Vascular Smooth Muscle Cells in Aorta by Activating NAMPT/PARP1 in Mice.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Age-dependent cytokine surge in blood precedes cancer diagnosis.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- ACSS2 drives senescence-associated secretory phenotype by limiting purine biosynthesis through PAICS acetylation.Nature communications · 2025Article
- Amodiaquine ameliorates stress-induced premature cellular senescence via promoting SIRT1-mediated HR repair.Cell death discovery · 2024Article
- The Structures, Functions, and Roles of Class III HDACs (Sirtuins) in Neuropsychiatric Diseases.Cells · 2024Review
- Review
- YIPF2 regulates genome integrity.Cell & bioscience · 2024Article
- The transcription factor PAX5 activates human LINE1 retrotransposons to induce cellular senescence.EMBO reports · 2024Article
- Senescence-Associated Heterochromatin Foci Suppress γ-H2AX Focus Formation Induced by Radiation Exposure.International journal of molecular sciences · 2024Article
- Sirtuins in kidney diseases: potential mechanism and therapeutic targets.Cell communication and signaling : CCS · 2024Review
- TKT-PARP1 axis induces radioresistance by promoting DNA double-strand break repair in hepatocellular carcinoma.Oncogene · 2024Article
- Effects of p53 and ATRX inhibition on telomeric recombination in aging fibroblasts.Frontiers in oncology · 2024Article
- Sirtuin 6 activation rescues the age-related decline in DNA damage repair in primary human chondrocytes.Aging · 2023Article
- Genomic Instability and Epigenetic Changes during Aging.International journal of molecular sciences · 2023Review
- IDDoR: a novel reporter mouse system for simultaneous and quantitative in vivo analysis of both DNA double-strand break repair pathways.Protein & cell · 2023Article
- Loss of the receptors ER, PR and HER2 promotes USP15-dependent stabilization of PARP1 in triple-negative breast cancer.Nature cancer · 2023Article
- Multifaceted Influence of Histone Deacetylases on DNA Damage Repair: Implications for Hepatocellular Carcinoma.Journal of clinical and translational hepatology · 2023Review
- DNA damage and repair in age-related inflammation.Nature reviews. Immunology · 2023Review
37 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Genomic instability is a hallmark of aging tissues. Genomic instability may arise from the inefficient or aberrant function of DNA double-stranded break (DSB) repair. DSBs are repaired by homologous recombination (HR) and nonhomologous DNA end joining (NHEJ). HR is a precise pathway, whereas NHEJ frequently leads to deletions or insertions at the repair site. Here, we used normal human fibroblasts with a chromosomally integrated HR reporter cassette to examine the changes in HR efficiency as cells progress to replicative senescence. We show that HR declines sharply with increasing replicative age, with an up to 38-fold decrease in efficiency in presenescent cells relative to young cells. This decline is not explained by a reduction of the number of cells in S/G(2)/M stage as presenescent cells are actively dividing. Expression of proteins involved in HR such as Rad51, Rad51C, Rad52, NBS1, and Sirtuin 6 (SIRT6) diminished with cellular senescence. Supplementation of Rad51, Rad51C, Rad52, and NBS1 proteins, either individually or in combination, did not rescue the senescence-related decline of HR. However, overexpression of SIRT6 in "middle-aged" and presenescent cells strongly stimulated HR repair, and this effect was dependent on mono-ADP ribosylation activity of poly(ADP-ribose) polymerase (PARP1). These results suggest that in aging cells, the precise HR pathway becomes repressed giving way to a more error-prone NHEJ pathway. These changes in the processing of DSBs may contribute to age-related genomic instability and a higher incidence of cancer with age. SIRT6 activation provides a potential therapeutic strategy to prevent the decline in genome maintenance.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.