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Mitochondrial dysfunction and cellular senescence are two hallmarks of aging that drive a progressional renal decline; however, the underlying molecular mechanisms and endogenous regulators behind these processes remain incompletely understood. The metabolism of polyunsaturated fatty acids by CYP450 enzymes produces numerous bioactive lipid mediators that can be further metabolized by soluble epoxide hydrolase (sEH) and microsomal epoxide hydrolase (mEH) into diol metabolites, often with reduced biological effects. The objective of this study was to assess renal mitochondrial alterations and cellular senescence in young and aged wild-type (WT) and sEH-deficient (sEH null) female mice. We found aged sEH null mice exhibited better physiological health, as reflected by lower frailty index scores and reduced circulating levels of GDF-15 levels, creatinine, and urea nitrogen. Notably, the expression of both sEH and mEH was significantly elevated in aged WT kidneys, accompanied by increased expression of the kidney injury marker (\n                    <jats:italic>Kim-1<\/jats:italic>\n                    ) and evidence of structural abnormalities. In contrast, sEH deletion attenuated the age-related upregulation of senescence markers (p53, p21, p16) and SASP components (MCP-1, IL-1\u03b2, and caspase-1), as well as the inflammatory zBP1 expression and downstream interferons. Additionally, sEH deletion preserved age-related disruption of mitochondrial dynamics, content, and respiratory function. Together, these data suggest that sEH deletion confers renoprotective effects in aging, characterized by improved systemic health, reduced renal injury and inflammation as preserves mitochondrial integrity and function.\n                  <\/jats:p>","DOI":"10.1007\/s11357-025-01814-3","type":"journal-article","created":{"date-parts":[[2025,7,26]],"date-time":"2025-07-26T06:18:20Z","timestamp":1753510700000},"page":"2707-2725","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Alterations in mitochondria and cellular senescence in aged sEH null female kidneys"],"prefix":"10.1007","volume":"48","author":[{"given":"Ala","family":"Yousef","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liye","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mobina","family":"Heidari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andy","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Kondraciuk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristen A.","family":"Yee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Mengel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0764-3933","authenticated-orcid":false,"given":"John M.","family":"Seubert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,7,26]]},"reference":[{"issue":"10","key":"1814_CR1","doi-asserted-by":"publisher","first-page":"1359","DOI":"10.1001\/jamainternmed.2021.4813","volume":"181","author":"P Liu","year":"2021","unstructured":"Liu P, Quinn RR, Lam NN, Elliott MJ, Xu Y, James MT, et al. 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