Disuse atrophy of human skeletal muscle: cell signaling and potential interventions.

In response to atrophic stimuli, physical alterations include decreases in fiber diameter and contractile protein content. Despite the fact that these phenotypical alterations have been well characterized, the signaling pathways that mediate these adaptations are still under investigation. There have been significant advances in the past few years delineating signal transduction pathways that regulate protein turnover. In the process of evaluating the effect of various atrophy-inducing stimuli on signal transduction pathways in skeletal muscle, it is apparent that differences do exist concerning both transcriptional and translational adaptations. To this end, it is hypothesized that the processes responsible for invoking skeletal muscle atrophy are unique, despite similar upstream signals and downstream phenotypical adaptations. If this is the case, countermeasures to attenuate atrophy may be more effective if they are designed to accommodate molecular alterations specific to the atrophic stimulus. The aim of this review was to characterize the recent work in humans elucidating the molecular basis of skeletal muscle atrophy in response to immobilization, unloading, spinal cord injury, and detraining to highlight the possibility that all skeletal muscle atrophy is not the same. With an increased understanding of the unique signaling pathways that regulate skeletal muscle protein turnover in the face of various atrophy models, it is possible to exploit these pathways to develop countermeasures to prevent or attenuate atrophy. Eugenics, gene therapy, pharmacology, nutritional, and physical countermeasures are discussed concerning their potential to treat or mitigate atrophy.