ArticleAging2023
Sirtuin 6 activation rescues the age-related decline in DNA damage repair in primary human chondrocytes.
Article in Aging, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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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.
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Who cites it
13 citing papers in PubMed, 16 citations in OpenAlex.
- Phase 1, Single-Center, Double-Blind, Randomized, Placebo-Controlled Studies of the Safety, Tolerability, and Pharmacokinetics of Single and Multiple Ascending Oral Doses of the Sirtuin 6 Activator SP-624 in Healthy Adults.Clinical pharmacology in drug development · 2025Trial
- Critical role of Sirtuin 6 (SIRT6) in osteoarthritis chondrocytes: the interaction among various biological processes.Annals of medicine · 2026Review
- Subtype-specific sirtuin expression signatures link mitochondrial-epigenetic networks to breast cancer survival.GeroScience · 2026Article
- Comparative whole-genome analyses of articular chondrocytes and skin fibroblasts reveal distinct genome instability landscapes in mesenchymal cell types.PLoS genetics · 2026Article
- Comparative whole-genome analyses of articular chondrocytes and skin fibroblasts reveal distinct genome instability landscapes in mesenchymal cell types.bioRxiv : the preprint server for biology · 2026Article
- The quantified immune-aging dysregulation index: a large-language model-powered method for annotating and quantifying systems-level dysregulation.Frontiers in artificial intelligence · 2026Article
- The Influence of Sirtuin 6 on Chondrocyte Senescence in Osteoarthritis Under Aging: Focusing on Mitochondrial Dysfunction and Oxidative Stress.Antioxidants (Basel, Switzerland) · 2025Review
- Klotho protein: a multifaceted regulator in aging and cancer dynamics.Molecular biology reports · 2025Review
- Sirt6 deficiency promotes senescence and age-associated intervertebral disc degeneration in mice.Bone research · 2025Article
- Review
- SIRT6 loss causes intervertebral disc degeneration in mice by promoting senescence and SASP status.bioRxiv : the preprint server for biology · 2024Article
- DNA Damage and Cellular Senescence in Osteoarthritis: An Unexpected Role for Interferon Regulatory Factor 1 in Chondrocyte DNA Repair.Arthritis & rheumatology (Hoboken, N.J.) · 2024Article
- ER stress-induced YAP upregulation leads to chondrocyte phenotype loss in age-related osteoarthritis.Frontiers in pharmacology · 2024Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
While advanced age is widely recognized as the greatest risk factor for osteoarthritis (OA), the biological mechanisms behind this connection remain unclear. Previous work has demonstrated that chondrocytes from older cadaveric donors have elevated levels of DNA damage as compared to chondrocytes from younger donors. The purpose of this study was to determine whether a decline in DNA repair efficiency is one explanation for the accumulation of DNA damage with age, and to quantify the improvement in repair with activation of Sirtuin 6 (SIRT6). After acute damage with irradiation, DNA repair was shown to be more efficient in chondrocytes from young (≤45 years old) as compared to middle-aged (50-65 years old) or older (>70 years old) cadaveric donors. Activation of SIRT6 with MDL-800 improved the repair efficiency, while inhibition with EX-527 reduced the rate of repair and increased the percentage of cells that retain high levels of damage. In addition to affecting repair after acute damage, treating chondrocytes from older donors with MDL-800 for 48 hours significantly reduced the amount of baseline DNA damage. Chondrocytes isolated from the knees of mice between 4 months and 22 months of age revealed both an increase in DNA damage with aging, and a decrease in DNA damage following MDL-800 treatment. Lastly, treating murine cartilage explants with MDL-800 lowered the percentage of chondrocytes with high p16 promoter activity, which supports the concept that using SIRT6 activation to maintain low levels of DNA damage may prevent the initiation of senescence.
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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.