University of California, Berkeley, Berkeley, CA, USA.
University of Maryland School of Medicine, Baltimore, MD, USA.
Geroscience. 2024 Feb;46(1):183-190. doi: 10.1007/s11357-023-01016-9. Epub 2023 Nov 24.
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.
除了在运动和运动中发挥作用外，肌肉在广泛的代谢过程中也起着至关重要的作用，这些过程有助于改善健康或降低患病风险。与年龄相关的肌肉丧失被称为肌肉减少症。肌肉是胰岛素刺激葡萄糖摄取的主要部位，也是基础代谢率的最大组成部分，它直接和间接地影响骨密度，产生具有肌肉和其他组织（包括大脑）多效性的肌肉因子，并储存必需氨基酸，这些氨基酸对于减少食物摄入和压力期间蛋白质合成的维持至关重要。因此，毫不奇怪，骨骼肌健康的恶化，通常表现为肌肉质量和肌肉力量的下降，既是慢性疾病、残疾和丧失独立性的强有力危险因素和主要后果，也是死亡率的最强危险因素之一。然而，骨骼肌仍然是所有组织中最具可塑性的组织之一，其蛋白质合成和降解的速度会根据身体活动和不活动、炎症以及营养和激素状况而迅速变化。这使得开发增加肌肉质量（或防止肌肉减少）的药物治疗方法成为几十年来的一个重要目标。然而，尽管最近在肌肉蛋白代谢的分子和细胞调节方面取得了显著进展，但仍没有批准用于治疗影响数百万老年人的肌肉减少症的药物。本文的目的是描述缺乏新的和有效的药物治疗方法来治疗与年龄相关的疾病和丧失独立性的最重要危险因素之一的可能原因。
