Giovannini Silvia, Marzetti Emanuele, Borst Stephen E, Leeuwenburgh Christiaan
Department of Aging and Geriatric Research, University of Florida, Gainesville, USA.
Mech Ageing Dev. 2008 Oct;129(10):593-601. doi: 10.1016/j.mad.2008.08.001. Epub 2008 Aug 13.
Aging is associated with progressive decline of skeletal muscle mass and function. This condition, termed sarcopenia, is associated with several adverse outcomes, including loss of autonomy and mortality. Due to the high prevalence of sarcopenia, a deeper understanding of its pathophysiology and possible remedies represents a high public health priority. Evidence suggests the existence of a relationship between declining growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels and age-related changes in body composition and physical function. Therefore, the age-dependent decline of GH and IGF-1 serum levels may promote frailty by contributing to the loss of muscle mass and strength. Preclinical studies showed that infusion of angiotensin II produced a marked reduction in body weight, accompanied by decreased serum and muscle levels of IGF-1. Conversely, overexpression of muscle-specific isoform of IGF-1 mitigates angiotensin II-induced muscle loss. Moreover, IGF-1 serum levels have been shown to increase following angiotensin converting enzyme inhibitors (ACEIs) treatment. Here we will review the most recent evidence regarding age-related changes of the GH/IGF-1 axis and its modulation by several interventions, including ACEIs which might represent a potential novel strategy to delay the onset and impede the progression of sarcopenia.
衰老与骨骼肌质量和功能的逐渐衰退相关。这种状况被称为肌肉减少症,与多种不良后果相关,包括自主性丧失和死亡率增加。由于肌肉减少症的高患病率,深入了解其病理生理学及可能的治疗方法是一项高度优先的公共卫生事项。有证据表明,生长激素(GH)和胰岛素样生长因子-1(IGF-1)水平下降与身体成分和身体功能的年龄相关变化之间存在关联。因此,GH和IGF-1血清水平随年龄的下降可能通过导致肌肉质量和力量的丧失而促进身体虚弱。临床前研究表明,输注血管紧张素II会导致体重显著下降,同时血清和肌肉中的IGF-1水平降低。相反,肌肉特异性IGF-1同工型的过表达可减轻血管紧张素II诱导的肌肉损失。此外,血管紧张素转换酶抑制剂(ACEIs)治疗后,IGF-1血清水平已被证明会升高。在此,我们将综述关于GH/IGF-1轴与年龄相关变化及其通过多种干预措施(包括ACEIs)进行调节的最新证据,ACEIs可能是延缓肌肉减少症发病和阻止其进展的一种潜在新策略。