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Skeletal muscle is the most abundant tissue in healthy individuals and it has important roles in health beyond voluntary movement. The overall mass and energy requirements of skeletal muscle require it to be metabolically active and flexible to multiple energy substrates. The tissue has evolved to be largely load dependent and it readily adapts in a number of positive ways to repetitive overload, such as various forms of exercise training. However, unloading from extended bed rest and/or metabolic derangements in response to trauma, acute illness, or severe pathology, commonly results in rapid muscle wasting. Decline in muscle mass contributes to multimorbidity, reduces function, and exerts a substantial, negative impact on the quality of life. The principal mechanisms controlling muscle mass have been well described and these cellular processes are intricately regulated by exercise. Accordingly, exercise has …