{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:57:24Z","timestamp":1792789044100,"version":"4.5.0"},"reference-count":170,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T00:00:00Z","timestamp":1760313600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Shanghai Key Lab of Human Performance","award":["11DZ2261100"],"award-info":[{"award-number":["11DZ2261100"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Osteoarthritis (OA) is one of the most common joint diseases worldwide, which is characterized by degenerative changes in articular cartilage and secondary osteophyte formation. Numerous factors influence OA, including aging, obesity, joint injury and chronic overloading. Among them, the senescence of chondrocytes is one of the key factors leading to OA. Chondrocyte senescence can trigger inflammatory responses, extracellular matrix (ECM) degradation, mitochondrial dysfunction and oxidative stress (OS), and autophagy. Sirtuin 6 (SIRT6), as a deacetylase related to aging, can regulate chondrocyte senescence and plays a certain part in OA. SIRT6 regulates the number and membrane integrity of mitochondria, alleviates excessive Reactive Oxygen Species (ROS) in mitochondria and reduces inflammation-mediated mitochondrial damage. In addition, SIRT6 can also regulate the activity of antioxidant enzymes, inhibit excessive ROS induced by inflammatory factors, and alleviate OS. However, as aging progresses, the activity of SIRT6 will decrease. Activating the activity of SIRT6 becomes a potential therapeutic target and has a certain alleviating effect on the development of OA. The supplementation of nicotinamide adenine dinucleotide (NAD+) precursors and SIRT6-specific activators can increase SIRT6, alleviate chondrocyte senescence, and reduce OA. This paper aims to focus on mitochondrial dysfunction and OS to explore SIRT6\u2019s effects on OA chondrocytes\u2019 senescence under aging and summarize the potential therapeutic targets for activating SIRT6 to provide assistance for the improvement of OA.<\/jats:p>","DOI":"10.3390\/antiox14101228","type":"journal-article","created":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T13:13:27Z","timestamp":1760361207000},"page":"1228","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["The Influence of Sirtuin 6 on Chondrocyte Senescence in Osteoarthritis Under Aging: Focusing on Mitochondrial Dysfunction and Oxidative Stress"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-5180-4017","authenticated-orcid":false,"given":"Huiying","family":"Zhao","sequence":"first","affiliation":[{"name":"School of Exercise and Health, Shanghai University of Sports, Shanghai 200438, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0401-7363","authenticated-orcid":false,"given":"Wei","family":"Wu","sequence":"additional","affiliation":[{"name":"School of Athletic Performance, Shanghai University of Sports, Shanghai 200438, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1697","DOI":"10.1002\/art.34453","article-title":"Osteoarthritis: A disease of the joint as an organ","volume":"64","author":"Loeser","year":"2012","journal-title":"Arthritis Rheum."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1016\/S0140-6736(14)60802-3","article-title":"Osteoarthritis","volume":"386","author":"Palmer","year":"2015","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Chen, X., Tang, H., Lin, J., and Zeng, R. 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