{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T04:10:12Z","timestamp":1791864612287,"version":"4.3.4"},"reference-count":48,"publisher":"The Endocrine Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>IGF-1 receptor (IGF-1R) signaling is implicated in cardiac hypertrophy and longevity. However, the role of IGF-1R in age-related cardiac remodeling is only partially understood. We therefore sought to determine whether the deletion of the IGF-1R in cardiomyocytes might delay the development of aging-associated myocardial pathologies by examining 2-year-old male cardiomyocyte-specific IGF-1R knockout (CIGF1RKO) mice. Aging was associated with the induction of IGF-1R expression in hearts. Cardiomyocytes hypertrophied with age in wild-type (WT) mice. In contrast, the cardiac hypertrophic response associated with aging was blunted in CIGF1RKO mice. Concomitantly, fibrosis was reduced in aged CIGF1RKO compared with aged WT hearts. Expression of proinflammatory cytokines such as IL-1\u03b1, IL-1\u03b2, IL-6, and receptor activator of nuclear factor-\u03baB ligand was increased in aged WT hearts, but this increase was attenuated in aged CIGF1RKO hearts. Phosphorylation of Akt was increased in aged WT, but not in aged CIGF1RKO, hearts. In cultured cardiomyocytes, IGF-1 induced senescence as demonstrated by increased senescence-associated \u03b2-galactosidase staining, and a phosphoinositide 3-kinase inhibitor inhibited this effect. Furthermore, inhibition of phosphoinositide 3-kinase significantly prevented the increase in IL-1\u03b1, IL-1\u03b2, receptor activator of nuclear factor-\u03baB ligand, and p21 protein expression by IGF-1. These data reveal an essential role for the IGF-1-IGF-1R-Akt pathway in mediating cardiomyocyte senescence.<\/jats:p>","DOI":"10.1210\/en.2015-1709","type":"journal-article","created":{"date-parts":[[2015,10,15]],"date-time":"2015-10-15T13:33:04Z","timestamp":1444915984000},"page":"336-345","source":"Crossref","is-referenced-by-count":93,"title":["Deletion of IGF-1 Receptors in Cardiomyocytes Attenuates Cardiac Aging in Male Mice"],"prefix":"10.1210","volume":"157","author":[{"given":"Sangmi","family":"Ock","sequence":"first","affiliation":[{"name":"Division of Endocrinology and Metabolism (S.O., J.A., H.M.K., J.K.), Seoul, 156\u2013755, Korea;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wang Soo","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Cardiology (W.S.L.), Seoul, 156\u2013755, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jihyun","family":"Ahn","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism (S.O., J.A., H.M.K., J.K.), Seoul, 156\u2013755, Korea;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun Min","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism (S.O., J.A., H.M.K., J.K.), Seoul, 156\u2013755, Korea;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, and Departments of Anesthesiology (H.K.) 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