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Omega\u20103 polyunsaturated fatty acids (PUFAs) are essential fatty acids for humans, exerting their functions via free fatty acid receptor 4 (FFAR4). Clinical studies indicate that omega\u20103 PUFAs supplementation shows benefits for the elderly population and CKD patients, but these results remain controversial. Herein, we found that omega\u20103 PUFAs alleviated renal fibrosis and tubular senescence in aged mice, adenine diet\u2010induced CKD mice, and unilateral ureteral obstruction (UUO) mice. Meanwhile, omega\u20103 fatty acid receptor FFAR4 expression in tubular epithelial cells (TECs) were down\u2010regulated in the old population and CKD patients, positively correlated with renal dysfunction. Systemic or TEC\u2010specific knockout of FFAR4 aggravated renal aging and CKD in mice. Mechanically, FFAR4 agonism increases the production of endogenous PPAR\u03b3 activator 15\u2010deoxy\u2010\u220612,14\u2010Prostaglandin J2 (15d\u2010PGJ2), and improves PPAR\u03b3\u2010dependent tubular epithelial cell senescence, which was indicated by anti\u2010aging marker Klotho expression, senescence\u2010associated \u03b2\u2010galactosidase (SA\u2010\u03b2\u2010gal) activity, and profibrotic factor TGF\u2010\u03b21 secretion. The study demonstrated a novel role of FFAR4 from senescent TECs on fibroblast activation via paracrine effects and highlighted the therapeutic effects of omega\u20103 PUFAs with their receptor FFAR4 as an attractive drug target against renal aging and CKD.<\/jats:p>","DOI":"10.1111\/acel.70546","type":"journal-article","created":{"date-parts":[[2026,5,23]],"date-time":"2026-05-23T14:34:42Z","timestamp":1779546882000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Tubular Omega\u20103 Fatty Acid Receptor\n                    <scp>FFAR4<\/scp>\n                    Deficiency Aggravated Renal Aging and Chronic Kidney Disease"],"prefix":"10.1111","volume":"25","author":[{"given":"Letian","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Nephrology, Institute of Kidney Diseases West China Hospital of Sichuan University  Chengdu 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