Pathways for Skeletal Muscle Hypertrophy

保持骨骼肌的完整性对于正常的运动功能至关重要。在成年过程中，骨骼肌质量和力量逐渐丧失，导致老年人常见的运动障碍。骨骼肌丧失也可能导致遗传性疾病患者的功能障碍，这些患者的支架结缔组织将肌肉纤维连接在一起，如杜兴氏营养不良症。因此，了解肌肉细胞生长的生物学以及对运动和衰老等环境压力的反应对于健康的日常功能至关重要。在初步研究中，我们定义了一种新的生化途径，我们认为这是肌肉变大变强的能力基础。在这一应用中，我们建议通过使用细胞培养模型和在动物身上进行的实验来严格评估这一途径在肌肉生长中的作用。这项研究的结果将对大量主要的临床疾病，如心力衰竭、与年龄相关的肌肉无力和肌肉疾病有直接的治疗益处。

Maintenance of skeletal muscle integrity is critical for normal locomotor function. During adulthood skeletal muscle mass and strength is progressively lost which leads to locomotor impairment common in the elderly. Loss of skeletal muscle may also contribute to functional impairment in patients with inherited disorders of the scaffolding connective tissue that hold muscle fibres together, such as Duchenne's dystrophy. Understanding the biology of muscle cell growth and responses to environmental stresses such as exercise and ageing is, therefore, critical to healthy daily functioning. In preliminary studies we have defined a novel biochemical pathway which we believe underlies the ability of muscle to grow larger and stronger. In this application, we propose to rigorously evaluate the role of this pathway in muscle growth by experiments performed both with cell culture models and in animals. The findings of this study would have direct therapeutic benefit for a large number of major clinical conditions, such as heart failure, age-related muscular weakness and muscle diseases.