PDF(Pubmed)
Abstract：
In addition to the role of skeletal muscle in movement and locomotion, muscle plays a critical role in a broad array of metabolic processes that can contribute to improved health or risk of disease. The age-associated loss of muscle has been termed sarcopenia. The muscle is the primary site of insulin-stimulated glucose disposal and the largest component of basal metabolic rate, directly and indirectly affects bone density, produces myokines with pleiotropic effect on muscle and other tissues including the brain, and stores essential amino acids essential for the maintenance of protein synthesis during periods of reduced food intake and stress. As such, not surprisingly deterioration of skeletal muscle health, typically operationalized as decline of muscle mass and muscle strength is both a powerful risk factor and main consequence of chronic diseases, disability, and loss of independence, and it is one of the strongest risk factors for mortality. However, skeletal muscle remains one of the most plastic of all tissues, with rapid changes in rates of protein synthesis and degradation in response to physical activity and inactivity, inflammation, and nutritional and hormonal status. This has made the development of pharmacological therapies to increase muscle mass (or prevent loss), an important goal for decades. However, while remarkable advances in the understanding of molecular and cellular regulation of muscle protein metabolism have occurred recently, there are no approved drugs for the treatment of sarcopenia, the loss of skeletal muscle affecting millions of older people. The goal of this paper is to describe the possible reasons for the lack of new and effective pharmacotherapies to treat one of the most important risk factors for age-associated disease and loss of independence.
摘要：
除了骨骼肌在运动和运动中的作用，肌肉在广泛的代谢过程中起着关键作用，这些代谢过程可以改善健康或疾病风险。与年龄相关的肌肉损失被称为肌肉减少症。肌肉是胰岛素刺激的葡萄糖处置的主要部位，是基础代谢率的最大组成部分，直接和间接影响骨密度，产生对肌肉和包括大脑在内的其他组织具有多效性作用的肌细胞因子，并储存在食物摄入减少和压力减少期间维持蛋白质合成所必需的必需氨基酸。因此，骨骼肌健康恶化并不令人惊讶，通常，由于肌肉质量和肌肉力量的下降是慢性疾病的强大风险因素和主要后果，残疾,失去独立性，它是死亡的最大危险因素之一。然而,骨骼肌仍然是所有组织中最具可塑性的组织之一，随着身体活动和不活动而导致的蛋白质合成和降解速率的快速变化，炎症,营养和荷尔蒙状况。这使得药物疗法的发展，以增加肌肉质量（或防止损失），几十年来的重要目标。然而,虽然最近在了解肌肉蛋白质代谢的分子和细胞调节方面取得了显著进展，没有批准的治疗肌肉减少症的药物，影响数百万老年人的骨骼肌损失。本文的目的是描述缺乏新的有效药物疗法来治疗与年龄相关的疾病和失去独立性的最重要风险因素之一的可能原因。
