{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T17:08:58Z","timestamp":1790874538264,"version":"4.1.0"},"reference-count":45,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2018,8,31]],"date-time":"2018-08-31T00:00:00Z","timestamp":1535673600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008783","name":"National Research Council of Science and Technology","doi-asserted-by":"publisher","award":["CRC-15-02-KRIBB"],"award-info":[{"award-number":["CRC-15-02-KRIBB"]}],"id":[{"id":"10.13039\/501100008783","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2018,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Aging is associated with an inevitable and universal loss of cell homeostasis and restricts an organism's lifespan by an increased susceptibility to diseases and tissue degeneration. The glucose uptake associated with producing energy for cell survival is one of the major causes of ROS production under physiological conditions. However, the overall mechanisms by which glucose uptake results in cellular senescence remain mysterious. In this study, we found that TXNIP deficiency accelerated the senescent phenotypes of MEF cells under high glucose condition. TXNIP<jats:sup>\u2010\/\u2010<\/jats:sup> MEF cells showed greater induced glucose uptake and ROS levels than wild\u2010type cells, and <jats:italic>N<\/jats:italic>\u2010acetylcysteine (NAC) treatment rescued the cellular senescence of TXNIP<jats:sup>\u2010\/\u2010<\/jats:sup> MEF cells. Interestingly, TXNIP<jats:sup>\u2010\/\u2010<\/jats:sup> MEF cells showed continuous activation of AKT during long\u2010term subculture, and AKT signaling inhibition completely blocked the cellular senescence of TXNIP<jats:sup>\u2010\/\u2010<\/jats:sup> MEF cells. In addition, we found that TXNIP interacted with AKT via the PH domain of AKT, and their interaction was increased by high glucose or H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> treatment. The inhibition of AKT activity by TXNIP was confirmed using western blotting and an in vitro kinase assay. TXNIP deficiency in type 1 diabetes mice (Akita) efficiently decreased the blood glucose levels and finally increased mouse survival. However, in normal mice, TXNIP deficiency induced metabolic aging of mice and cellular senescence of kidney cells by inducing AKT activity and aging\u2010associated gene expression. Altogether, these results suggest that TXNIP regulates cellular senescence by inhibiting AKT pathways via a direct interaction under conditions of glucose\u2010derived metabolic stress.<\/jats:p>","DOI":"10.1111\/acel.12836","type":"journal-article","created":{"date-parts":[[2018,8,31]],"date-time":"2018-08-31T10:24:02Z","timestamp":1535711042000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["TXNIP regulates AKT\u2010mediated cellular senescence by direct interaction under glucose\u2010mediated metabolic stress"],"prefix":"10.1111","volume":"17","author":[{"given":"Hangsak","family":"Huy","sequence":"first","affiliation":[{"name":"Immunotherapy Convergence Research Center Korea Research Institute of Bioscience and Biotechnology (KRIBB) Daejeon Korea"},{"name":"Department of Functional Genomics University of Science and Technology (UST) Daejeon 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