Oxidative stress and disuse muscle atrophy

Abstract

Purpose of review This review will discuss the evidence both for and against the concept that reactive oxygen species (ROS) play an important role in the regulation of inactivity-induced skeletal muscle atrophy. Recent findings It is well established that prolonged skeletal muscle inactivity causes muscle fiber atrophy and a decrease in muscle force production. This disuse-induced muscle atrophy is the consequence of a loss in muscle protein resulting from increased protein degradation and decreased protein synthesis. Recent studies suggest that oxidative stress can influence cell signaling pathways that regulate both muscle protein breakdown and synthesis during prolonged periods of disuse. Specifically, it is feasible that increased ROS production in muscle fibers can promote increased proteolysis and also depress protein synthesis during periods of skeletal muscle inactivity. Summary Although it is established that oxidants can participate in the regulation of protein turnover in cells, there remains debate as to whether oxidative stress is required for disuse skeletal muscle atrophy. Nonetheless, based on emerging evidence we conclude that increased ROS production in skeletal muscles significantly contributes to inactivity-induced muscle atrophy.

Loss of muscle mass: Current developments in cachexia and sarcopenia focused on biomarkers and treatment

“…42 Furthermore, increased oxidative stress activates the NFκB pathway. 43 Surprisingly, an inhibition of NFκB via the IkappaB kinase complex only partially rescues the phenotype of the cachectic gastrocnemius in a murine model of cancer cachexia. 44 The FoxO family members consist of three isoforms as FoxO1, FoxO3, and FoxO4.…”

p53 suppresses muscle differentiation at the myogenin step in response to genotoxic stress

“…[21][22][23][24][25][62][63][64] Moreover, we are intrigued by a possible connection between repression of myogenin by p53 and muscle aging. Skeletal muscle aging is characterized by muscle atrophy and a decline in muscle function and regenerative capacity.…”

Nutritional strategies to counteract muscle atrophy caused by disuse and to improve recovery

“…It has been postulated that this oxidative stress may play an important role in the process of muscle atrophy during disuse (75) . Even if its origin remains to be clearly determined (110) , one of the possible mechanisms could be a decreased production of endogenous antioxidant defences in response to immobilisation (12,111 -113) , due to the decrease in protein synthesis associated with muscle atrophy (12,114) . In rodents, immobilised muscles exhibit either a decrease (101,115) or an increase (30) in muscle glutathione concentration.…”

“…As immobilisation is associated with local inflammation and oxidative stress, it may be postulated that these phenomena lead to an increased anabolism threshold, translating into the anabolic resistance of skeletal muscle to food intake. Antioxidant supplementation has been shown to be an effective countermeasure to fight oxidative stress in a wide variety of tissue types and conditions (110,175) , and it is speculated that this might be an efficient approach to reduce muscle wasting associated with muscle disuse (176) . Similar results have been obtained with antiinflammatory compounds (136) that improve muscle mass maintenance under atrophying conditions.…”

“…This inflammatory response parallels tissue infiltration by macrophages (129 -131) . These inflammatory cells are able to produce the cytokine TNF-a which could later activate the inflammatory NF-kB pathway (75,110) . Up-regulation of other pro-inflammatory cytokines (for example, IL-1b and IL-6) has also been observed in response to muscle immobilisation (39) .…”