Molecular Approaches to Reversing Muscle Wasting in COPD. The Role of Resistance Training and Protein Supplementation

慢性病是21世纪人类健康面临的一大挑战。预计未来几年，英国和世界各地的慢性病负担将会增加。慢性阻塞性肺疾病(COPD)是一种重要的胸部慢性疾病，是老年人致残的主要原因。肌肉萎缩和虚弱是慢性阻塞性肺疾病的重要特征。肌肉萎缩的患者残疾程度更高，预后更差，需要更多的医疗资源。肌肉体积和功能的丧失很重要，因为这可能是潜在肺部疾病通常不可逆转的情况下可治疗的后果。这种方法的价值通过体育锻炼的好处得到了证明，这在慢性阻塞性肺疾病中已经得到了清楚的证明。然而，人们对COPD患者肌肉萎缩和虚弱的原因以及体育锻炼改善肌肉功能的机制知之甚少。我们最近在健康的年轻人和老年人中发现了参与调节肌肉损耗和生长的基因，并证明了这些基因的功能受到不动和运动时间的深刻影响。最近的研究还表明，在健康人的运动训练中，饮食中补充蛋白质可以促进肌肉生长。我们将把这些观察扩展到研究慢性阻塞性肺疾病临床环境中的肌肉萎缩和生长。我们将与同年龄段的健康志愿者比较，研究最近被发现对调节COPD患者肌肉生长和消瘦起重要作用的基因的功能。我们还将研究为期八周的下肢力量训练计划对这些基因功能的影响。这将帮助我们了解训练是如何起作用的，以及训练如何影响调节肌肉生长的基因。在训练时补充额外的膳食蛋白质可能是有益的。我们将通过随机分配研究中的患者在每一轮训练后接受富含蛋白质的饮料或非营养的安慰剂来检验这一理论。我们还将在研究期间测量肌肉体积和肌肉功能。这项研究将为肌肉萎缩和虚弱的遗传机制提供新的见解，以及这些基因的功能如何受到训练和营养等干预措施的影响。这一信息将是旨在改善慢性阻塞性肺病等慢性病肌肉功能的新疗法开发方面的重大进展。

Chronic diseases are a major challenge for human health in the 21st century. The UK and worldwide burden of chronic disease is expected to increase in future years. Chronic Obstructive Pulmonary Disease (COPD) is an important chronic disease of the chest and is a leading cause of disability among older people. Muscle wasting and weakness is an important feature of COPD. Patients with muscle wasting are more disabled, have a poorer prognosis and require more healthcare resources. Loss of muscle bulk and function is important because it may be a treatable consequence of a condition in which the underlying lung disease is usually irreversible. The value of this approach is illustrated by the benefits of physical training, which have been clearly demonstrated in COPD. However, little is known about the causes of muscle wasting and weakness or the mechanisms by which physical training improves muscle function in COPD. We have recently identified genes involved in the regulation of muscle wasting and growth in healthy young and elderly humans and demonstrated that the functioning of these genes is profoundly affected by periods of immobility and exercise. Recent work has also demonstrated that dietary supplementation of protein enhances muscle growth during exercise training in healthy humans. We will extend these observations to study muscle wasting and growth in the clinical setting of COPD. We will study the functioning of genes recently identified as important in the regulation of muscle growth and wasting in patients with COPD compared with healthy volunteers of the same age. We will also study the effects of an eight-week lower limb strength-training programme on the functioning of these genes. This will help us understand how training works and how training affects the genes that regulate muscle growth. It may be beneficial to supplement individuals with additional dietary protein at the time of training. We will test this theory by randomly allocating patients in the study to receive a protein rich drink or a non-nutritive placebo after each bout of training. We will also measure muscle bulk and muscle function during the study. This research will provide new insights into the genetic mechanisms of muscle wasting and weakness and how the functioning of these genes can be influenced by interventions such as training and nutrition. This information will be a significant advance in the development of new treatments aimed at improving muscle function in chronic diseases such as COPD.