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The PRDF1 and RIZ1 homology domain (PRDM) protein exhibits robust transcriptional regulatory activities and governs a wide range of biological processes. However, its roles in cellular senescence remain unclear. Here, this work demonstrates that PRDM16, a member of the PRDM protein family, decreases significantly in multiple organs of aged mice compared to young mice. Global\n                    <jats:italic>Prdm16<\/jats:italic>\n                    deletion contributes to cellular senescence in various organs, including the kidneys, heart, lungs, hippocampus, stomach, and gut, leading to accelerated aging\u2010related organ injury. Furthermore, tubular\u2010specific\n                    <jats:italic>Prdm16<\/jats:italic>\n                    deletion aggravates irradiation\u2010induced kidney aging and aging\u2010related kidney diseases in irradiated mice subjected to ischemia\u2010reperfusion surgery. Exogenous PRDM16 gene delivery by lentivirus effectively attenuates cellular senescence in vitro and in vivo. Mechanistically, PRDM16 improves glutathione metabolism and inhibits oxidative DNA damage, which is a driving force of senescence. Specifically, PRDM16 upregulates the transcription of glutathione S\u2010transferase mu 1 (GSTM1) by binding to its promoter region. Transfection with GSTM1 reverses PRDM16 deficiency\u2010induced cellular senescence and kidney aging. Collectively, these results provide a potential target for the investigation of anti\u2010aging therapies.\n                  <\/jats:p>","DOI":"10.1002\/advs.202501233","type":"journal-article","created":{"date-parts":[[2025,9,14]],"date-time":"2025-09-14T08:01:33Z","timestamp":1757836893000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["PRDM16 Reduces Cellular Senescence by Upregulating GSTM1"],"prefix":"10.1002","volume":"12","author":[{"given":"Qian","family":"Yuan","sequence":"first","affiliation":[{"name":"Department of Nephrology Union Hospital Tongji Medical College Huazhong University of Science and Technology  Wuhan 430022 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuting","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Nephrology Union Hospital Tongji Medical College Huazhong University of Science and Technology  Wuhan 430022 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Nephrology Union Hospital Tongji Medical College Huazhong University of Science and Technology  Wuhan 430022 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaru","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Nephrology Union Hospital Tongji Medical College Huazhong University of Science and Technology  Wuhan 430022 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingcun","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Nephrology Union Hospital Tongji Medical College Huazhong University of Science and Technology  Wuhan 430022 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Nephrology Union Hospital Tongji Medical College Huazhong University of Science and Technology  Wuhan 430022 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youhua","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Organ Failure Research National Clinical Research Center of Kidney Disease and Division of Nephrology Nanfang Hospital Southern Medical University Guangzhou 510515 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3565-8024","authenticated-orcid":false,"given":"Chun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Nephrology Union Hospital Tongji Medical College Huazhong University of Science and Technology  Wuhan 430022 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,14]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0457-8"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2022.11.001"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI64098"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature16932"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4000"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI158450"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00020.2018"},{"key":"e_1_2_9_8_1","volume":"11","author":"Liu Y.","year":"2024","journal-title":"Integr. 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