The injured athlete: Genetic profiling of skeletal muscle atrophy with limb immobilisation

Greater understanding of the aetiology of skeletal muscle atrophy and loss of muscle function during periods of unloading is important for injury management of athletes. The aim of this project is to quantify changes in global gene expression of human skeletal muscle in response to 14 days of immobilisation. Fifty healthy young men will have a leg placed in a full-length cast for 14 days. Quadriceps mass will be quantified before and after the 14 day intervention using magnetic resonance imaging to determine muscle atrophy, and pre- and post-intervention muscle biopsy samples will be collected for subsequent RNA-sequencing of changes in inducible gene expression in response to short-term muscle unloading. These data will provide new information on early transcriptional reprogramming with muscle disuse in human skeletal muscle.

Characterising the molecular profile of muscle wasting when physically active individuals undertake an enforced period of complete immobilisation will provide new information on the genetic bases of skeletal muscle atrophy. The primary aim of the proposed study is to determine changes in inducible gene expression in the early (3 d) and short-term (14 d) immobilisation period. The research question is novel and will have the capacity to inform sports medicine and exercise science in characterising individuals ‘at-risk’ of rapid degeneration of muscle mass with disuse or those that may be “protected” from muscle loss with short-term unloading. The use of the RNA-sequencing analysis will provide superior data than any previous studies examining genetic profiles associated with disuse atrophy.