{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T03:29:58Z","timestamp":1773372598495,"version":"3.50.1"},"reference-count":27,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T00:00:00Z","timestamp":1748476800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Health"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: One of the most debated topics in experimental and clinical endocrinology is the impact of hypo- and hyper-somatotropism on the extension\/shortening of the lifespan, the results of experimental, clinical, and epidemiological studies being extremely conflicting. Biological age, a surrogate of lifespan, can be measured through different methods, including the age-related epigenetic modifications of DNA. Objective: The present study aimed to evaluate the biological (epigenetic) age and age acceleration in a group of growth hormone (GH)-deficient (GHD) children (F\/M = 5\/5; age: 11.0 \u00b1 2.7 years), treated with recombinant human GH (rhGH) for 6 months at a daily dose of 0.025\u20130.035 mg\/kg. Results: Treatment with rhGH significantly increased height velocity and circulating insulin-like growth factor 1 (IGF-1) levels. Biological and chronological ages were significantly correlated at baseline and after 6 months of rhGH replacement therapy. Treatment with rhGH reduced age acceleration, an effect that became significant only after adjustment for IGF-1. In a linear regression model for longitudinal data, after adjustment for rhGH treatment, age acceleration was significantly associated with IGF-1 levels, an effect missing when considering the interaction rhGH treatment \u00d7 age acceleration at 6 months of rhGH treatment. Conclusions: (rh)GH, when administered to GHD children, exerts anti-ageing effects, which become evident after removal of the presumably pro-ageing effects of IGF-1.<\/jats:p>","DOI":"10.3390\/jcm14113840","type":"journal-article","created":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T04:27:58Z","timestamp":1748579278000},"page":"3840","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Evaluation of Epigenetic Age Acceleration in Growth Hormone (GH)-Deficient Children After 6 Months of Recombinant Human GH Replacement Therapy: Anti-Ageing GH vs. Pro-Ageing Insulin-like Growth Factor 1 (IGF-1)?"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2489-9108","authenticated-orcid":false,"given":"Antonello E.","family":"Rigamonti","sequence":"first","affiliation":[{"name":"Department of Clinical Sciences and Community Health, Dipartimento di Eccellenza 2023\u20132027, University of Milan, 20129 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0370-9598","authenticated-orcid":false,"given":"Valentina","family":"Bollati","sequence":"additional","affiliation":[{"name":"EPIGET Lab, Department of Clinical Sciences and Community Health, Dipartimento di Eccellenza 2023\u20132027, University of Milan, 20122 Milan, Italy"},{"name":"Occupational Health Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara","family":"Favero","sequence":"additional","affiliation":[{"name":"EPIGET Lab, Department of Clinical Sciences and Community Health, Dipartimento di Eccellenza 2023\u20132027, University of Milan, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benedetta","family":"Albetti","sequence":"additional","affiliation":[{"name":"EPIGET Lab, Department of Clinical Sciences and Community Health, Dipartimento di Eccellenza 2023\u20132027, University of Milan, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9145-5400","authenticated-orcid":false,"given":"Adele","family":"Bondesan","sequence":"additional","affiliation":[{"name":"Experimental Laboratory for Auxo-endocrinological Research, Istituto Auxologico Italiano, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), 28824 Piancavallo-Verbania, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicoletta","family":"Marazzi","sequence":"additional","affiliation":[{"name":"Experimental Laboratory for Auxo-endocrinological Research, Istituto Auxologico Italiano, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), 20145 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6884-3766","authenticated-orcid":false,"given":"Silvano G.","family":"Cella","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences and Community Health, Dipartimento di Eccellenza 2023\u20132027, University of Milan, 20129 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9620-4133","authenticated-orcid":false,"given":"Alessandro","family":"Sartorio","sequence":"additional","affiliation":[{"name":"Experimental Laboratory for Auxo-endocrinological Research, Istituto Auxologico Italiano, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), 28824 Piancavallo-Verbania, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1038\/nrendo.2013.67","article-title":"The GH\/IGF-1 axis in ageing and longevity","volume":"9","author":"Junnila","year":"2013","journal-title":"Nat. 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