Control of muscle size during disuse, disease, and aging

Abstract

Skeletal muscle is a highly plastic tissue. For example, muscle hypertrophies during strength training and increases its oxidative capacity in response to endurance training. Conditions associated with disuse, however, are also accompanied by adaptations, of which atrophy and a slow-to-fast transition are most prominent. Fast and slow muscles respond differently to disuse. The different response of muscle to different models of disuse reveals that loading is most important, but that also activity level, neurotrophic factors, and ageing play a part in determining the mass, morphology, contractile properties, and fatigability of a muscle. Muscle loss during disuse is a result, at least in part, of apoptosis. Finally, skeletal muscle wasting and remodelling during ageing and chronic disorders, such as chronic heart failure and chronic obstructive pulmonary disease, are not entirely attributable to disuse, but are also related to secondary consequences of the disease, most notably inflammation. Besides activating other pathways, we present evidence that inflammation during ageing and chronic disorders causes muscle wasting via alterations in abundance and/or activity of muscle specific transcription factors and induction of apoptosis, and that systemic inflammation rather than disuse is the primary cause of muscle wasting during ageing and chronic disorders.