{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T12:33:33Z","timestamp":1793277213756,"version":"4.5.0"},"reference-count":105,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Alliance of Cardiovascular Researchers"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The age-related decline in growth hormone (GH) secretion, termed the somatopause, parallels the structural and functional deterioration of the ageing heart. How this endocrine withdrawal translates into myocardial failure at the molecular level remains incompletely mapped. GH\/insulin-like growth factor 1 (IGF-1) signalling acts via phosphoinositide 3-kinase\/Akt\/mechanistic target of rapamycin and Ras\/mitogen-activated protein kinase\/c-Myc cascades on four processes central to cardiac ageing: Akt-dependent nuclear retention of telomerase reverse transcriptase (TERT), established primarily in non-cardiomyocyte models; peroxisome proliferator-activated receptor-\u03b3 coactivator 1\u03b1 (PGC-1\u03b1)-driven mitochondrial biogenesis; suppression of the p53\/p16INK4a senescence programme; and metabolic-epigenetic regulation of cell-cycle competence via \u03b1-ketoglutarate\/lysine demethylase 5 and Jumonji domain-containing protein 3 chromatin gating. In mouse cardiomyocytes, positive transcription elongation factor b is rate limiting for Myc-driven proliferation, plausibly explaining why adult cardiomyocytes retain latent cell-cycle machinery yet rarely divide. A candidate GH-releasing hormone receptor\u2013hypoxia-inducible factor 1\u03b1 axis, supported by a single recent experimental study, is examined as an emerging hypothesis for cell-type-selective cardioprotection independent of systemic GH. We integrate these strands along a single tractable axis: IGF-1\/Akt\/TERT\/p53\/PGC-1\u03b1 with metabolic-epigenetic modulation. The 2025 Marra trial (NCT03775993; 64 randomized, 45 completers; surrogate and functional endpoints not powered for clinical events) reports that physiological GH restoration improves peak VO2 (+3.1 vs. \u22121.8\u2005mL\/kg\/min, P &amp;lt; 0.01), New York Heart Association class, and quality of life in heart failure (HF) with confirmed GH deficiency. A meta-analysis of 25 studies quantifies the U-shaped IGF-1\u2013HF relationship, with the HF vs. control IGF-1 difference derived from six of those studies. Plasma proteomic organ-ageing signatures show accelerated cardiac ageing is associated with 2.5-fold heart-failure risk. We present a hypothesis-generating framework identifying GH\/IGF-1 axis restoration as a candidate determinant of heart-failure progression, warranting event-driven confirmation.<\/jats:p>","DOI":"10.1093\/cvr\/cvag225","type":"journal-article","created":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T11:37:35Z","timestamp":1791286655000},"source":"Crossref","is-referenced-by-count":0,"title":["Growth hormone and ageing cardiomyocytes"],"prefix":"10.1093","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6687-139X","authenticated-orcid":false,"given":"Eckhard U","family":"Alt","sequence":"first","affiliation":[{"name":"Applied Stem Cell Laboratory, Department of Medicine\/Cardiology, Tulane University School of Medicine , 1430 Tulane Avenue, New Orleans, LA 70112 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4520-8150","authenticated-orcid":false,"given":"Reza","family":"Izadpanah","sequence":"additional","affiliation":[{"name":"Applied Stem Cell Laboratory, Department of Medicine\/Cardiology, Tulane University School of Medicine , 1430 Tulane Avenue, New Orleans, LA 70112 ,","place":["USA"]},{"name":"Department of Surgery, Tulane University School of Medicine , 1430 Tulane Avenue, New Orleans, LA 70112 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,10,8]]},"reference":[{"key":"2026102907520912400_cvag225-B1","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1161\/01.CIR.0000048892.83521.58","article-title":"Arterial and cardiac aging: major shareholders in cardiovascular disease 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