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

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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.