Rigamonti Antonello E, Bollati Valentina, Favero Chiara, Albetti Benedetta, Bondesan Adele, Marazzi Nicoletta, Cella Silvano G, Sartorio Alessandro
Department of Clinical Sciences and Community Health, Dipartimento di Eccellenza 2023-2027, University of Milan, 20129 Milan, Italy.
EPIGET Lab, Department of Clinical Sciences and Community Health, Dipartimento di Eccellenza 2023-2027, University of Milan, 20122 Milan, Italy.
J Clin Med. 2025 May 29;14(11):3840. doi: 10.3390/jcm14113840.
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. 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 ± 2.7 years), treated with recombinant human GH (rhGH) for 6 months at a daily dose of 0.025-0.035 mg/kg. 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 × age acceleration at 6 months of rhGH treatment. (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.
实验和临床内分泌学中最具争议的话题之一是生长激素分泌不足和分泌过多对寿命延长/缩短的影响，实验、临床和流行病学研究的结果极不一致。生物学年龄作为寿命的一个替代指标，可以通过不同的方法来测量，包括与年龄相关的DNA表观遗传修饰。本研究旨在评估一组生长激素（GH）缺乏（GHD）儿童（男/女=5/5；年龄：11.0±2.7岁）的生物学（表观遗传）年龄和年龄加速情况，这些儿童接受了6个月的重组人生长激素（rhGH）治疗，每日剂量为0.025 - 0.035mg/kg。rhGH治疗显著提高了身高增长速度和循环胰岛素样生长因子1（IGF-1）水平。在基线时以及rhGH替代治疗6个月后，生物学年龄和实际年龄显著相关。rhGH治疗降低了年龄加速，这种效果仅在对IGF-1进行调整后才变得显著。在一个针对纵向数据的线性回归模型中，在对rhGH治疗进行调整后，年龄加速与IGF-1水平显著相关，而在考虑rhGH治疗×rhGH治疗6个月时的年龄加速之间的相互作用时，这种效果并不明显。给GHD儿童使用（rh）GH会产生抗衰老作用，在消除了IGF-1可能的促衰老作用后，这种作用变得明显。
