Skeletal muscle wasting in cachexia and sarcopenia: molecular pathophysiology and impact of exercise training

Abstract

Skeletal muscle is the most abundant tissue in the human body, and the maintenance of its mass is essential to ensure basic function as locomotion, strength and respiration. The decision to synthesize or to break down skeletal muscle proteins is regulated by a network of signaling pathways that transmit external stimuli to intracellular factors regulating gene transcription. The tightly regulated balance of muscle protein breakdown and synthesis is disturbed in several distinct myopathies, but also in two pathologies: sarcopenia and cachexia. In recent years, it became evident that in these two muscle wasting disorders specific regulating molecules are increased in expression (e.g. members of the ubiquitin-proteasome system, myostatin, apoptosis inducing factors), whereas other factors (e.g. insulin-like growth factor 1) are down-regulated. So far, not many treatment options to fight the muscle loss are available. One of the most promising approaches is exercise training that, due to its multifactorial effects, can act on several signaling pathways. Therefore, this review will concentrate on specific alterations discussed in the current literature that are present in the skeletal muscle of both muscle wasting disorders. In addition, we will focus on exercise training as an intervention strategy.

Fig. 1

Schematic drawing of aetiological factors leading to cachexia or sarcopenia and finally to muscle wasting. Exercise training as an intervention is able to modify this course

Fig. 2

Schematic drawing of factors involved in regulating muscle mass (a) and the impact of exercise training on these factors (b). Factors influenced by exercise training are shaded in grey