{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T06:34:42Z","timestamp":1792996482003,"version":"4.5.0"},"reference-count":83,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"SELENOBESITY","award":["ANR-23-CE14-0049"],"award-info":[{"award-number":["ANR-23-CE14-0049"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Antioxidants &amp; Redox Signaling"],"abstract":"<jats:sec>\n                    <jats:title>Aims:<\/jats:title>\n                    <jats:p>\n                      Selenoprotein T (SELENOT) is an endoplasmic reticulum (ER)-resident thioredoxin-like oxidoreductase implicated in redox and calcium (Ca\n                      <jats:sup>2+<\/jats:sup>\n                      ) homeostasis and protein quality control. Although SELENOT is highly expressed in the brain, its role in hypothalamic pro-opiomelanocortin (POMC) neurons, which regulate energy balance, remains poorly understood. We investigated whether SELENOT is required for maintaining ER homeostasis and neuronal integrity in POMC neurons.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Using CRISPR-edited and siRNA-silenced POMC neuronal models together with a POMC-specific SELENOT knockout mouse, we demonstrated that SELENOT loss induces a senescent-like phenotype including cellular hypertrophy, loss of neurite outgrowth, senescence-associated \u03b2-galactosidase activity, increased P16 and P21 expression, and acquisition of senescence-associated secretory phenotype. Senescence markers were elevated not only in SELENOT-deficient POMC neurons but also throughout the surrounding arcuate nucleus\n                      <jats:italic toggle=\"yes\">in\u00a0vivo<\/jats:italic>\n                      , suggesting propagation of a pro-inflammatory microenvironment. Mechanistically, prolonged SELENOT deficiency produced selective activation of the ATF6\u03b1 arm of the unfolded protein response, depletion of ER Ca\n                      <jats:sup>2+<\/jats:sup>\n                      stores, and profound alterations in\n                      <jats:italic toggle=\"yes\">N<\/jats:italic>\n                      -glycan maturation. Notably, leptin-induced POMC processing and secretion were spared. Glycomics revealed a shift toward immature glycans, whereas thiol-trapping proteomics identified candidate SELENOT interactors linked to ER Ca\n                      <jats:sup>2+<\/jats:sup>\n                      regulation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Innovation and Conclusions:<\/jats:title>\n                    <jats:p>\n                      This study provides the first evidence that SELENOT deficiency is sufficient to trigger cellular senescence in POMC neurons, acting as a central regulator integrating ER proteostasis, Ca\n                      <jats:sup>2+<\/jats:sup>\n                      homeostasis, redox adaptation, and glycosylation. These results reveal a previously unrecognized mechanism potentially linking neuronal senescence to hypothalamic dysfunction and suggest that SELENOT-dependent pathways may represent therapeutic targets for obesity, metabolic disease, and age-related neuroendocrine disorders.\n                      <jats:italic toggle=\"yes\">Antioxid. Redox Signal.<\/jats:italic>\n                      00, 000\u2013000.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/15230864261494912","type":"journal-article","created":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T02:31:43Z","timestamp":1791426703000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Loss of Selenot in POMC Neurons Disrupts ER Homeostasis and Induces A Senescent-like Phenotype"],"prefix":"10.1177","author":[{"given":"C\u00e9dric","family":"Jehan","sequence":"first","affiliation":[{"name":"Univ Rouen Normandie, INSERM, INSERM U1239, Normandie Univ, Rouen, France."},{"name":"Institute of Research and Innovation in Biomedicine (IRIB), Rouen, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"In\u00e8s","family":"Drissa","sequence":"additional","affiliation":[{"name":"Univ Rouen Normandie, INSERM, INSERM U1239, Normandie Univ, Rouen, France."},{"name":"Institute of Research and Innovation in Biomedicine (IRIB), Rouen, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorthe","family":"Cartier","sequence":"additional","affiliation":[{"name":"Univ Rouen Normandie, INSERM, INSERM U1239, Normandie Univ, Rouen, France."},{"name":"Institute of Research and Innovation in Biomedicine (IRIB), Rouen, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Bucharles","sequence":"additional","affiliation":[{"name":"Univ Rouen Normandie, INSERM, INSERM U1239, Normandie Univ, Rouen, France."},{"name":"Institute of Research and Innovation in Biomedicine (IRIB), Rouen, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Az\u00e9nor","family":"Abgrall","sequence":"additional","affiliation":[{"name":"Univ Rouen Normandie, INSERM, INSERM U1239, Normandie Univ, Rouen, France."},{"name":"Institute of Research and Innovation in Biomedicine (IRIB), 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