Mechanisms of muscle atrophy and hypertrophy: implications in health and disease

Abstract

Skeletal muscle is the protein reservoir of our body and an important regulator of glucose and lipid homeostasis. Consequently, the growth or the loss of muscle mass can influence general metabolism, locomotion, eating and respiration. Therefore, it is not surprising that excessive muscle loss is a bad prognostic index of a variety of diseases ranging from cancer, organ failure, infections and unhealthy ageing. Muscle function is influenced by different quality systems that regulate the function of contractile proteins and organelles. These systems are controlled by transcriptional dependent programs that adapt muscle cells to environmental and nutritional clues. Mechanical, oxidative, nutritional and energy stresses, as well as growth factors or cytokines modulate signaling pathways that, ultimately, converge on protein and organelle turnover. Novel insights that control and orchestrate such complex network are continuously emerging and will be summarized in this review. Understanding the mechanisms that control muscle mass will provide therapeutic targets for the treatment of muscle loss in inherited and non-hereditary diseases and for the improvement of the quality of life during ageing.

MyD88‐mediated signaling intercedes in neurogenic muscle atrophy through multiple mechanisms

“…Muscle wasting in many catabolic conditions including denervation involves the activation of the UPS and the autophagy-lysosomal system which mediate the loss of bulk of muscle proteins. 2,40 The activity of these proteolytic systems is stimulated through upstream activation of specific signaling pathways such p38MAPK, AMPK, and myostatin/Smad2/3 and FOXO and NF-κB transcription factors. By contrast, the activation of Akt/mTOR signaling pathway prevents the activation of UPS and autophagy in skeletal muscle.…”

“…Indeed, levels of inflammatory cytokines have been found to remain elevated in skeletal muscle and in circulation in humans and animal models of various chronic disease states. 2 However, the role of inflammatory mediators in skeletal muscle wasting in disuse conditions, such as denervation remains enigmatic. Nuclear factor-κB (NF-κB) is a pro-inflammatory transcription factor that has been found to play an important role in muscle atrophy in distinct conditions.…”

“…17,[20][21][22] It is now increasingly evidenced that different catabolic stimuli can employ distinct molecular pathways to induce skeletal muscle atrophy. 2,3,10 However, the role of TLR-MyD88 signaling in the regulation of skeletal muscle mass in disuse conditions such as denervation remains completely unknown.…”

Nutraceuticals in the Prevention and Treatment of the Muscle Atrophy

“…It is characterized by muscle mass loss, muscle weakness, and disability, all of which are associated with an impaired quality of life [1]. Various stimuli, such as aging, genetics, denervation, starvation, unhealthy lifestyle (i.e., sedentariness, high fat diet (HFD)), systemic pathologies (i.e., diabetes, inflammation, cancer), and long-term drug therapy (i.e., glucocorticoids) are known to further skeletal muscle loss and weakness [2][3][4]. On one hand, the increase in life expectancy and the elderly population, in conjunction with the high prevalence of muscle atrophy in the elderly, create an enormous socioeconomic burden.…”

An Analysis of Differentially Expressed Coding and Long Non-Coding RNAs in Multiple Models of Skeletal Muscle Atrophy

“…Muscle atrophy is induced by myostatin, NF-κβ, and glucocorticoid signaling, which activate the ubiquitin-proteasome and autophagy-lysosome systems to increase muscle protein breakdown [14][15][16]. In contrast, insulin-like growth factor-1 (IGF-1)/Akt/mammalian target of rapamycin (mTOR) and β-adrenergic pathways inhibit muscle atrophy by promoting muscle protein synthesis [17]. The recent discoveries of microRNAs have provided novel insights into the regulation of skeletal muscle mass [18].…”