{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T12:07:57Z","timestamp":1779451677122,"version":"3.53.1"},"reference-count":133,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T00:00:00Z","timestamp":1779408000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Postoperative cognitive dysfunction (POCD) is a common complication in older surgical patients. While its pathogenesis remains unclear, ferroptosis\u2014an iron-dependent form of cell death driven by lipid peroxidation\u2014has emerged as a key mechanism in neurodegeneration. This review proposes that aging creates a ferroptosis-prone environment in the brain through iron dyshomeostasis, impaired antioxidant defenses, and enrichment of polyunsaturated fatty acids, and that surgical trauma and anesthetic exposure may trigger ferroptosis by activating interconnected pathways such as neuroinflammation, blood-brain barrier disruption, and oxidative stress, leading to neuronal injury in cognition-critical regions like the hippocampus. However, the available evidence is largely correlative, and whether ferroptosis acts as a proximal driver of neuronal death or as a late consequence of pre-existing damage remains undetermined. We dissect the core molecular machinery (GPX4, ACSL4, NCOA4, Nrf2) and emerging regulators (MD2\/Hepcidin, CPT1A, RUNX1\/RBM47\/cGAS-STING, miRNAs, mitophagy, gut microbiota-exosome axis). Therapeutic strategies including iron chelators, lipophilic antioxidants, natural products, physical therapies, and nanomaterials are reviewed, but most remain preclinical. Elucidating the role of ferroptosis may open new avenues for early diagnosis, targeted prevention, and effective treatment, provided that causality can be rigorously established.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1836516","type":"journal-article","created":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T11:28:01Z","timestamp":1779449281000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Ferroptosis: an emerging key mechanism linking aging, surgical and anesthetic exposure to postoperative cognitive dysfunction"],"prefix":"10.3389","volume":"17","author":[{"given":"Danxia","family":"Jiang","sequence":"first","affiliation":[{"name":"The Second Clinical Medical College of Zhejiang Chinese Medical University","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiaolan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Urology, Lanxi People's Hospital","place":["Jinhua, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yin","family":"Tong","sequence":"additional","affiliation":[{"name":"Department of Urology, Lanxi People's Hospital","place":["Jinhua, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kecheng","family":"Lou","sequence":"additional","affiliation":[{"name":"Department of Urology, Lanxi People's Hospital","place":["Jinhua, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haicheng","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Urology, The Sixth People's Hospital of Huizhou","place":["Huizhou, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3238\/arztebl.2017.0110","article-title":"Cognitive reserve and the risk of postoperative 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