How Acute and Chronic Exercise Regulate Muscle Atrophic Genes to Mitigate Sarcopenia: A Narrative Review

Muscle atrophy is defined as the reduction in muscle mass and strength resulting from a decrease in muscle fiber size and protein content. Muscle atrophy may result from physical inactivity, aging, starvation, or extended periods of limb immobilization. In addition, there are clinical conditions that are intrinsically associated with progressive muscle wasting, such as cancer, diabetes, or chronic heart failure, among others, as these conditions often involve a catabolic hormonal status or a decrease in neuromuscular stimulation. Overall, muscle atrophy leads to significant loss of health and quality of life as it reduces the independence and mobility of individuals affected by this disorder. Physical inactivity is the most common cause of muscle atrophy, especially in older adults, as it increases inflammation factors (TNF-α, IL-1β, and IL-6) and glucocorticoid levels (e.g., cortisol), disrupts intracellular signaling (GH/IGF-1, testosterone, and myostatin), and triggers decreased signaling of growth factors, such as diminished phosphorylation of FoxO by Akt. As a result of this decreased signaling, FoxO translocates to the nucleus of the muscle cell and induces the expression of muscle atrophy-related genes such as ATROGIN-1 (formally designated as FBXO3, also known as MAFbx) and MuRF-1 (formally designated as TRIM-63, also known as IRF). The higher expression of the proteins encoded by these genes, Atrogin-1 and MuRF-1, activates the ubiquitin-proteasome system in the striated muscle tissue responsible for degrading and recycling damaged, misfolded, or unneeded proteins. Therefore, the lack of muscle activity due to prolonged physical inactivity leads to muscle protein degradation and ultimately to muscle wasting. In the elderly and other populations with clinical conditions, there is a progressive reduction in physical activity and changes in food intake that may accelerate the loss of muscle mass and function, as well as increase body fat, giving rise to the phenomenon of sarcopenia. These changes in body composition increase the risk of suffering from chronic diseases, with a clear impact on progressively reduced mobility and increased risk of falls. Acute and chronic exercise can partially interrupt this vicious cycle in older adults and sedentary populations with chronic diseases, as it can diminish muscle wasting by activating molecular mechanisms to enhance muscle growth. Specifically, exercise can enhance muscle protein synthesis by activating the mTOR pathway while reducing protein degradation by suppressing the expression of muscle atrophy genes. In this narrative review, we summarize the mechanisms of action of the genes associated with muscle atrophy, MuRF-1 and ATROGIN-1, and their differential expression patterns following experimental and clinical trials involving chronic and acute exercise exposure, along with other potential regulators implicated in muscle remodeling.