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Keywords:

  • proteolysis;
  • muscle wasting;
  • ubiquitin ligase;
  • NF-κB;
  • proteasome;
  • apoptosis;
  • microgravity;
  • exercise;
  • growth factor;
  • nutrition

Abstract

  • • 
    Introduction
  • • 
    Overview of signalling pathways involved in disuse-induced muscle atrophy
    • - 
      Changes in protein synthesis and associated signalling pathways
    • - 
      Several pathways contribute to increased protein degradation but to different extents
      • - 
        Akt/FOXO transcriptional control and induction of the ubiquitin ligase pathway
      • - 
        NF-κB pathways activated during disuse atrophy
    • - 
      Additional events controlling muscle atrophy
      • - 
        Apoptotic pathways are involved depending on the atrophy models
      • - 
        Preferential role of myostatin in inhibiting hypertrophy rather than inducing atrophy
  • • 
    Different approaches to counteract muscle disuse-induced atrophy
    • - 
      Exercise and physical training
    • - 
      Nutritional aids
    • - 
      Manipulations of growth factors
    • - 
      Additional nutritional, ergogenic supplements and drugs
    • - 
      Combined countermeasures for optimized effects
  • • 
    Conclusion and perspectives

Disuse-induced skeletal muscle atrophy occurs following chronic periods of inactivity such as those involving prolonged bed rest, trauma and microgravity environments. Deconditioning of skeletal muscle is mainly characterized by a loss of muscle mass, decreased fibre cross-sectional area, reduced force, increased fatigability, increased insulin resistance and transitions in fibre types. A description of the role of specific transcriptional mechanisms contributing to muscle atrophy by altering gene expression during muscle disuse has recently emerged and focused primarily on short period of inactivity. A better understanding of the transduction pathways involved in activation of proteolytic and apoptotic pathways continues to represent a major objective, together with the study of potential cross-talks in these cellular events. In parallel, evaluation of the impact of countermeasures at the cellular and molecular levels in short- and long-term disuse experimentations or microgravity environments should undoubtedly and synergistically increase our basic knowledge in attempts to identify new physical, pharmacological and nutritional targets to counteract muscle atrophy. These investigations are important as skeletal muscle atrophy remains an important neuromuscular challenge with impact in clinical and social settings affecting a variety of conditions such as those seen in aging, cancer cachexia, muscle pathologies and long-term space exploration.