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This study revealed that the incidence of SUI is associated with mitochondrial homeostasis dysregulation following oxidative stress in the fibrous connective tissue of the pelvic floor. SIRT1 is an essential factor for maintaining mitochondrial homeostasis; however, its potential role and mechanism of action in SUI pathogenesis remain unclear. Both in\u00a0vitro and in\u00a0vivo, we observed that oxidative stress reduced SIRT1 expression to inhibit the PGC\u20101\u03b1\/NRF1\/TFAM and PINK1\/Parkin signalling pathways, eliciting impairment of mitochondrial biogenesis and mitophagy in L929 cells and SUI mice. Decreased SIRT1 levels induced endoplasmic reticulum (ER) stress and altered the structure of mitochondria\u2010associated membranes (MAMs), disrupting ER\u2010mitochondrial calcium homeostasis and exacerbting ROS accumulation. SIRT1 activation can restore mitochondrial function and the structure of MAMs and alleviate ER stress in fibroblasts, promoting anterior vaginal wall repair and improving urodynamic parameters in the SUI model. Our findings provide novel insights into the role and associated mechanism of SIRT1 in ameliorating oxidative stress\u2010induced mitochondrial dysfunction in fibroblasts of the anterior vaginal wall and propose SIRT1 as a potential therapeutic target for SUI.<\/jats:p>","DOI":"10.1111\/cpr.70009","type":"journal-article","created":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T04:03:36Z","timestamp":1740110616000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["<scp>SIRT1<\/scp>\n                    Alleviates Oxidative Stress\u2010Induced Mitochondrial Dysfunction and Mitochondria\u2010Associated Membrane Dysregulation in Stress Urinary Incontinence"],"prefix":"10.1111","volume":"58","author":[{"given":"Liying","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Gynecology and Obstetrics Renmin Hospital of Wuhan University  Wuhan People's Republic of 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