Effects of Various Muscle Disuse States and Countermeasures on Muscle Molecular Signaling

Abstract

Skeletal muscle is capable of changing its structural parameters, metabolic rate and functional characteristics within a wide range when adapting to various loading regimens and states of the organism. Prolonged muscle inactivation leads to serious negative consequences that affect the quality of life and work capacity of people. This review examines various conditions that lead to decreased levels of muscle loading and activity and describes the key molecular mechanisms of muscle responses to these conditions. It also details the theoretical foundations of various methods preventing adverse muscle changes caused by decreased motor activity and describes these methods. A number of recent studies presented in this review make it possible to determine the molecular basis of the countermeasure methods used in rehabilitation and space medicine for many years, as well as to identify promising new approaches to rehabilitation and to form a holistic understanding of the mechanisms of gravity force control over the muscular system.

Keywords: atrophy; disuse; disuse countermeasures; myosin phenotype; oxidative capacity; protein breakdown; protein synthesis; skeletal muscle; unloading.

Figure 1

Involvement of mechanical load and ground reaction force into the regulation of slow-type (type I) or fast-type (type II) skeletal muscle fibers.

Figure 2

Key signaling pathways regulating protein turnover during muscle disuse. Pointed arrows show activation; blocked arrows show inhibition.

Figure 3

Key signaling pathways regulating slow-to-fast fiber-type transformation and mitochondrial biogenesis during muscle disuse. Pointed arrows show activation; blocked arrows show inhibition.