Can antioxidants protect against disuse muscle atrophy?

Abstract

Long periods of skeletal muscle inactivity (e.g. prolonged bed rest or limb immobilization) results in a loss of muscle protein and fibre atrophy. This disuse-induced muscle atrophy is due to both a decrease in protein synthesis and increased protein breakdown. Although numerous factors contribute to the regulation of the rates of protein breakdown and synthesis in skeletal muscle, it has been established that prolonged muscle inactivity results in increased radical production in the inactive muscle fibres. Further, this increase in radical production plays an important role in the regulation of redox-sensitive signalling pathways that regulate both protein synthesis and proteolysis in skeletal muscle. Indeed, it was suggested over 20 years ago that antioxidant supplementation has the potential to protect skeletal muscles against inactivity-induced fibre atrophy. Since this original proposal, experimental evidence has implied that a few compounds with antioxidant properties are capable of delaying inactivity-induced muscle atrophy. The objective of this review is to discuss the role that radicals play in the regulation of inactivity-induced skeletal muscle atrophy and to provide an analysis of the recent literature indicating that specific antioxidants have the potential to defer disuse muscle atrophy.

Fig. 1

Illustration of several human conditions that promote inactivity-induced skeletal muscle atrophy, along with the corresponding animal model that is commonly used to study each condition

Fig. 2

Conservation of skeletal muscle mass depends on the balance between the rates of protein synthesis and degradation. An increase in the rate of protein synthesis relative to the rate of protein breakdown results in muscle hypertrophy. Conversely, an increase in the rate of protein breakdown relative to the rate of protein synthesis results in a net loss of muscle protein, and fibre atrophy occurs

Fig. 3

Steps leading from oxidative stress to muscle fibre atrophy. Inactivity-induced oxidative stress can promote muscle protein breakdown in three major ways: (1) oxidative stress increases gene expression of key proteolytic proteins; (2) cellular oxidative stress can activate selected proteases (i.e. calpain and caspase-3); and (3) oxidants can oxidize myofibrillar proteins and enhance their susceptibility to proteolytic processing. Further, oxidative stress can depress muscle protein synthesis. Collectively, this increased proteolysis and decreased muscle protein synthesis result in a net loss of muscle protein and, consequently, fibre atrophy. ROS reactive oxygen species

Fig. 4

Illustration of the potential role that antioxidants can play in protection against disuse muscle atrophy. Specifically, prolonged skeletal muscle inactivity leads to increased mitochondrial reactive oxygen species (ROS) production and oxidative stress in the inactive muscle fibres. This increased ROS production and oxidative stress can promote decreased protein synthesis and promote proteolysis in the muscle, leading to skeletal muscle atrophy. In theory, treatment with selected antioxidants can block disuse-induced oxidative stress and protect muscle fibres against disuse muscle atrophy