{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,22]],"date-time":"2026-02-22T10:46:42Z","timestamp":1771757202581,"version":"3.50.1"},"reference-count":44,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2017,5,29]],"date-time":"2017-05-29T00:00:00Z","timestamp":1496016000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["RO1\u2010DK80157"],"award-info":[{"award-number":["RO1\u2010DK80157"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["RO1\u2010DK089229"],"award-info":[{"award-number":["RO1\u2010DK089229"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K01AG038555"],"award-info":[{"award-number":["K01AG038555"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["CTSA 1UL1RR025767\u201001"],"award-info":[{"award-number":["CTSA 1UL1RR025767\u201001"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000041","name":"American Diabetes Association","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000041","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000965","name":"American Federation for Aging Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000965","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2017,8]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Older adults universally suffer from sarcopenia and approximately 60\u201370% are diabetic or prediabetic. Nonetheless, the mechanisms underlying these aging\u2010related metabolic disorders are unknown. <jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\u03baB has been implicated in the pathogenesis of several aging\u2010related pathologies including sarcopenia and type 2 diabetes and has been proposed as a target against them. <jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\u03baB also is thought to mediate muscle wasting seen with disuse, denervation, and some systemic diseases (<jats:italic>e.g<\/jats:italic>., cancer, sepsis). We tested the hypothesis that lifelong inhibition of the classical <jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\u03baB pathway would protect against aging\u2010related sarcopenia and insulin resistance. Aged mice with muscle\u2010specific overexpression of a super\u2010repressor I\u03baB\u03b1 mutant (<jats:styled-content style=\"fixed-case\">MISR<\/jats:styled-content>) were protected from insulin resistance. However, <jats:styled-content style=\"fixed-case\">MISR<\/jats:styled-content> mice were not protected from sarcopenia; to the contrary, these mice had decreases in muscle mass and strength compared to wild\u2010type mice. In <jats:styled-content style=\"fixed-case\">MISR<\/jats:styled-content> mice, <jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\u03baB suppression also led to an increase in proteasome activity and alterations in several genes and pathways involved in muscle growth and atrophy (<jats:italic>e.g<\/jats:italic>., myostatin). We conclude that the mechanism behind aging\u2010induced sarcopenia is <jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\u03baB independent and differs from muscle wasting due to pathologic conditions. Our findings also indicate that, while suppressing <jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\u03baB improves insulin sensitivity in aged mice, this transcription factor is important for normal muscle mass maintenance and its sustained inhibition is detrimental to muscle function.<\/jats:p>","DOI":"10.1111\/acel.12613","type":"journal-article","created":{"date-parts":[[2017,5,29]],"date-time":"2017-05-29T07:02:41Z","timestamp":1496041361000},"page":"847-858","source":"Crossref","is-referenced-by-count":25,"title":["Sustained <scp>NF<\/scp>\u03baB inhibition improves insulin sensitivity but is detrimental to muscle health"],"prefix":"10.1111","volume":"16","author":[{"given":"Ning","family":"Zhang","sequence":"first","affiliation":[{"name":"Barshop Institute for Longevity and Aging Studies University of Texas Health Science Center at San Antonio 15355 Lambda Drive San Antonio TX 78245 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph M.","family":"Valentine","sequence":"additional","affiliation":[{"name":"Barshop Institute for Longevity and Aging Studies University of Texas Health Science Center at San Antonio 15355 Lambda Drive San Antonio TX 78245 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"You","family":"Zhou","sequence":"additional","affiliation":[{"name":"Barshop Institute for Longevity and Aging Studies University of Texas Health Science Center at San Antonio 15355 Lambda Drive San Antonio TX 78245 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mengyao E.","family":"Li","sequence":"additional","affiliation":[{"name":"Barshop Institute for Longevity and Aging Studies University of Texas Health Science Center at San Antonio 15355 Lambda Drive San Antonio TX 78245 USA"},{"name":"Joslin Diabetes Center 1 Joslin Place Boston MA 02215 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E.","family":"Fischer","sequence":"additional","affiliation":[{"name":"Barshop Institute for Longevity and Aging Studies University of Texas Health Science Center at San Antonio 15355 Lambda Drive San Antonio TX 78245 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven N.","family":"Austad","sequence":"additional","affiliation":[{"name":"Barshop Institute for Longevity and Aging Studies University of Texas Health Science Center at San Antonio 15355 Lambda Drive San Antonio TX 78245 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pawel","family":"Osmulski","sequence":"additional","affiliation":[{"name":"Barshop Institute for Longevity and Aging Studies University of Texas Health Science Center at San Antonio 15355 Lambda Drive San Antonio TX 78245 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Gaczynska","sequence":"additional","affiliation":[{"name":"Barshop Institute for Longevity and Aging Studies University of Texas Health Science Center at San Antonio 15355 Lambda Drive San Antonio TX 78245 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven E.","family":"Shoelson","sequence":"additional","affiliation":[{"name":"Joslin Diabetes Center 1 Joslin Place Boston MA 02215 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Holly","family":"Van Remmen","sequence":"additional","affiliation":[{"name":"Barshop Institute for Longevity and Aging Studies University of Texas Health Science Center at San Antonio 15355 Lambda Drive San Antonio TX 78245 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hung I.","family":"Chen","sequence":"additional","affiliation":[{"name":"Greehey Children's Cancer Research Institute 8403 Floyd Curl Dr San Antonio TX 78229 USA"},{"name":"Department of Epidemiology and Biostatistics University of Texas Health Science Center at San Antonio 7703 Floyd Curl Dr San Antonio TX 78229 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