Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, Department of Emergency and Organ Transplantation, University of Bari School of Medicine, Piazza Giulio Cesare, 11, I-70124 Bari, Italy.
J Endocrinol. 2010 Jun;205(3):201-10. doi: 10.1677/JOE-09-0431. Epub 2010 Mar 2.
The widespread increase in life expectancy is accompanied by an increased prevalence of features of physical frailty. Signs and symptoms may include sarcopenia and osteopenia, reduced exercise capacity, and diminished sense of well-being. The pathogenesis of age-associated sarcopenia and osteopenia is multifactorial, and hormonal decline may be a contributing factor. Aging is associated with a progressive decrease in GH secretion, and more than 30% of elderly people have circulating IGF1 levels below the normal range found in the young. GH acts directly on target tissues, including skeletal muscle and bone among many others, but many effects are mediated indirectly by circulating (liver-derived) or locally produced IGF1. Aging is also associated with reduced insulin sensitivity which, in turn, may contribute to the impairment of IGF1 action. Recent experimental evidence suggests that besides the age-dependent decline in GH and IGF1 serum levels, the dysregulation of GH and IGF1 actions due to impairment of the post-receptor signaling machinery may contribute to the loss of muscle mass and osteopenia. This article will focus on the molecular mechanisms of impaired GH and IGF1 signaling and action in aging, and their role in the pathogenesis of sarcopenia and osteoporosis.
预期寿命的广泛延长伴随着身体脆弱特征的患病率增加。迹象和症状可能包括肌肉减少症和骨质疏松症、运动能力下降以及幸福感降低。与年龄相关的肌肉减少症和骨质疏松症的发病机制是多因素的，激素下降可能是一个促成因素。随着年龄的增长，生长激素的分泌逐渐减少，超过 30%的老年人的循环 IGF1 水平低于年轻人的正常范围。生长激素直接作用于靶组织，包括骨骼肌和骨骼等，但许多作用是通过循环（肝脏来源）或局部产生的 IGF1 间接介导的。衰老还与胰岛素敏感性降低有关，而胰岛素敏感性降低反过来又可能导致 IGF1 作用受损。最近的实验证据表明，除了与年龄相关的 GH 和 IGF1 血清水平下降之外，由于受体后信号转导机制受损导致 GH 和 IGF1 作用失调，可能导致肌肉质量减少和骨质疏松症。本文将重点介绍衰老过程中 GH 和 IGF1 信号转导和作用受损的分子机制，以及它们在肌肉减少症和骨质疏松症发病机制中的作用。
