{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T19:27:25Z","timestamp":1789068445337,"version":"build-2803163510"},"reference-count":31,"publisher":"Shared Science Publishers OG","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title id=\"abstract-title-5b9e3a4796a62eb8c706b57257N65731\">Abstract<\/jats:title>\n                  <jats:p id=\"paragraph-5b9e3a4796a62eb8c706b57258N65733\">\n                    Geroprotection aims at extending healthspan by delaying age-associated pathologies. Polyamines including spermine and spermidine are interconvertible metabolites whose longevity-promoting effects have traditionally been attributed to autophagy induction. In addition, recent evidence identifies spermine as an endogenous Fe\n                    <jats:sup>2+<\/jats:sup>\n                    chelator that suppresses ferroptosis, thereby complementing the autophagy-inducing activity of spermidine. Indeed, spermidine inhibits EP300 acetyltransferase activity and supports hypusination-dependent activation of TFEB, both leading to autophagy. However, enhanced autophagic flux may increase susceptibility to ferroptosis through ferritinophagy and lipid remodeling. In parallel, polyamine catabolism generates H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    and acrolein, both of which facilitate lipid peroxidation and ferroptotic demise. The discovery that spermine directly chelates redox-active Fe\n                    <jats:sup>2+<\/jats:sup>\n                    closes a conceptual gap by explaining how polyamine supplementation can promote longevity while avoiding excessive ferroptotic cell loss. Multiple lines of evidence including metabolomics, isotope tracing, cell-free lipid peroxidation systems, Fe\n                    <jats:sup>2+<\/jats:sup>\n                    -binding biophysics, mass spectrometry, Raman spectroscopy, nuclear magnetic resonance and disease models demonstrate that spermine limits labile iron and ferroptosis. Together, these findings support a unified model in which spermidine-driven autophagy and spermine-mediated ferroptosis inhibition cooperate to preserve tissue homeostasis and healthspan.\n                  <\/jats:p>","DOI":"10.15698\/cst2026.07.318","type":"journal-article","created":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T18:17:49Z","timestamp":1783621069000},"page":"49-52","source":"Crossref","is-referenced-by-count":1,"title":["Polyamine-mediated inhibition of ferroptosis contributes to 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