Harnessing muscle-specific atrophy susceptibility to disentangle the mechanisms of disuse atrophy in human skeletal muscle

骨骼周围的骨骼肌对运动至关重要。然而，骨骼肌对我们整个身体的健康也很重要，例如控制血糖（预防糖尿病）。我们肌肉的健康与身体活动水平直接相关。例如，缺乏身体活动会导致我们的肌肉萎缩，如果持续下去，就会导致健康状况不佳。相反，锻炼与改善健康有关。然而，有许多情况下，强制固定，例如，当从严重疾病或手术中恢复时，人们经常保持卧床数天甚至数周。同样，跌倒或骨折后，四肢可能会被固定以帮助骨骼愈合。本提案将调查人类肌肉因废用而萎缩的根本原因，并探索其时间过程（即大多数萎缩发生在最初几天？）我们将招募24名志愿者，他们将被分配到两组中的一组，他们将接受5天或15天的单腿固定（通过腿部支具），前后各有一个研究日。在这个研究日，我们将测量与骨骼肌和全身健康相关的许多因素，以了解这些因素如何受到固定的影响（例如肌肉建立/分解速率，肌肉血流量等）。我们还将研究腿部两种不同肌肉的这些反应：一种肌肉比另一种更容易肌肉萎缩。这种创新方法背后的想法是帮助我们确定调节肌肉损失的关键特征，这在“易萎缩”肌肉中应该更明显。总的来说，这个项目可能对理解废用期间的肌肉变化以及相关的健康结果具有开创性的意义。此外，该项目将为确定最佳策略（运动，营养或药物）以应对骨骼肌废用的不利影响奠定基础。

Skeletal muscles, which surround our bones, are crucial for movement. However, skeletal muscles are also important for the health of our whole body e.g. control of blood sugar (to prevent diabetes). The health of our muscles is directly linked to levels of physical (in)/activity. For example, physical inactivity causes our muscles to shrink in size and, if sustained, is linked to poor health outcomes. In contrast, exercise is linked with improved health. However, there are numerous situations where immobilization is enforced e.g. when recovering from a severe illness or operation, people often remain bedbound for days or even weeks. Similarly, after a fall or fracture, limbs may be immobilized to aid bone healing.This proposal will investigate the underlying reasons for muscle wasting in response to disuse in humans, and explore the time-course of this (i.e. does most wasting occur in the first few days?) We will recruit 24 volunteers who will be assigned to one of two groups, who will undergo either 5 or 15 days of single leg immobilization (via a leg brace) with a study day before and after. During this study day, we will measure a number of factors relating to skeletal muscle and whole-body health to see how these have been impacted by immobilization (e.g. muscle building/ breaking down rates, muscle blood flow etc.). We will also look at these responses in two different muscles of the leg: one that has been shown to be much more prone to muscle wasting than the other. The idea behind this innovative approach, is to help us identify the key features regulating muscle loss, which should be more pronounced in "atrophy susceptible" muscle.Taken together, this project could have groundbreaking implications for understanding muscle changes during periods of disuse, and associated health outcomes. Moreover, this project will form the basis for identifying optimal strategies (exercise, nutrition or drug-based) to counter the adverse effects of skeletal muscle disuse.