What is disuse atrophy?

Disuse atrophy, also known as disuse muscle atrophy or muscle wasting, refers to the loss of muscle mass and strength that occurs as a result of prolonged immobilization or inactivity. When muscles are not regularly used or subjected to mechanical loading, they undergo a process of gradual degeneration and weakening, leading to a decrease in muscle size, strength, and function.


The mechanisms underlying disuse atrophy involve a combination of muscle protein breakdown (catabolism) and reduced muscle protein synthesis (anabolism). Prolonged inactivity or immobilization reduces mechanical tension on muscles, leading to decreased activation of anabolic signaling pathways such as the mTOR (mammalian target of rapamycin) pathway, which regulates protein synthesis and muscle growth. Additionally, disuse can upregulate catabolic pathways such as the ubiquitin-proteasome system and autophagy, leading to increased breakdown of muscle proteins.


What is the relationship between disuse atrophy and oxidative stress?

The relationship between disuse atrophy and oxidative stress is complex and multifaceted. While oxidative stress is not the sole cause of disuse atrophy, it plays a significant role in mediating muscle damage and dysfunction during periods of inactivity or immobilization. Here’s how oxidative stress influences disuse atrophy:


  • Reactive Oxygen Species (ROS) Production: Disuse atrophy is associated with an increase in the production of reactive oxygen species (ROS) within muscle fibers. ROS, including superoxide radicals, hydrogen peroxide, and hydroxyl radicals, are generated as byproducts of cellular metabolism, particularly during periods of mitochondrial respiration. However, ROS production can be upregulated in response to disuse-induced changes in muscle metabolism and function, leading to oxidative stress.


  • Mitochondrial Dysfunction: Disuse atrophy is often accompanied by mitochondrial dysfunction, characterized by impaired mitochondrial biogenesis, reduced ATP production, and increased ROS generation. Mitochondria are the primary source of ROS production within muscle cells, and mitochondrial dysfunction can exacerbate oxidative stress by promoting the accumulation of ROS in the cytoplasm and intracellular compartments.


  • Oxidative Damage to Muscle Proteins: Oxidative stress can induce damage to muscle proteins, lipids, and DNA, contributing to muscle fiber degeneration and atrophy. ROS can react with and modify cellular components such as proteins, leading to protein oxidation, carbonylation, nitration, and fragmentation. Oxidative damage to muscle proteins disrupts their structure and function, impairing contractile activity, energy metabolism, and cellular signaling pathways involved in muscle growth and repair.


  • Activation of Catabolic Pathways: Oxidative stress can activate catabolic signaling pathways that promote muscle protein breakdown and degradation. For example, ROS can stimulate the ubiquitin-proteasome system, a major pathway for targeted protein degradation in muscle cells, leading to accelerated proteolysis and loss of muscle mass. Additionally, oxidative stress can activate autophagy, a cellular process that involves the degradation and recycling of damaged or dysfunctional cellular components, including organelles and proteins.


  • Impaired Antioxidant Defenses: Disuse atrophy can compromise the antioxidant defense mechanisms within muscle cells, leading to a disruption in the balance between ROS production and antioxidant capacity. Antioxidant enzymes such as superoxide dismutase, catalase, and glutathione peroxidase play a crucial role in neutralizing ROS and protecting cells from oxidative damage. However, during periods of disuse or immobilization, antioxidant defenses may become overwhelmed or depleted, allowing oxidative stress to accumulate and contribute to muscle dysfunction and atrophy.


Overall, oxidative stress plays a significant role in mediating muscle damage and dysfunction during disuse atrophy by promoting ROS production, mitochondrial dysfunction, oxidative damage to muscle proteins, activation of catabolic pathways, and impairment of antioxidant defenses.