Abstract
Muscle fatigue (MF) declines the capacity of muscles to complete a task over time at a constant load. MF is usually short-lasting, reversible, and is experienced as a feeling of tiredness or lack of energy. The leading causes of short-lasting fatigue are related to overtraining, undertraining/deconditioning, or physical injury. Conversely, MF can be persistent and more serious when associated with pathological states or following chronic exposure to certain medication or toxic composites. In conjunction with chronic fatigue, the muscle feels floppy, and the force generated by muscles is always low, causing the individual to feel frail constantly. The leading cause underpinning the development of chronic fatigue is related to muscle wasting mediated by aging, immobilization, insulin resistance (through high-fat dietary intake or pharmacologically mediated Peroxisome Proliferator-Activated Receptor (PPAR) agonism), diseases associated with systemic inflammation (arthritis, sepsis, infections, trauma, cardiovascular and respiratory disorders (heart failure, chronic obstructive pulmonary disease (COPD))), chronic kidney failure, muscle dystrophies, muscle myopathies, multiple sclerosis, and, more recently, coronavirus disease 2019 (COVID-19). The primary outcome of displaying chronic muscle fatigue is a poor quality of life. This type of fatigue represents a significant daily challenge for those affected and for the national health authorities through the financial burden attached to patient support. Although the origin of chronic fatigue is multifactorial, the MF in illness conditions is intrinsically linked to the occurrence of muscle loss. The sequence of events leading to chronic fatigue can be schematically denoted as: trigger (genetic or pathological) -> molecular outcome within the muscle cell -> muscle wasting -> loss of muscle function -> occurrence of chronic muscle fatigue. The present review will only highlight and discuss current knowledge on the molecular mechanisms that contribute to the upregulation of muscle wasting, thereby helping us understand how we could prevent or treat this debilitating condition.
Highlights
Muscle ArchitectureThe musculoskeletal system is one of the central organ systems in the body
Myostatin is important in the regulation of human muscle mass because it is involved in the control of both muscle protein synthesis by inhibiting anabolic signaling, which is translation initiation, through inhibiting the Akt/mechanistic target of rapamycin (mTOR))/p70S6k signaling pathways [47] and muscle protein breakdown [48]
We have recently shown that PPARδ agonism, used clinically to increase muscle fat oxidation, up-regulates pyruvate dehydrogenase kinase 4 (PDK4) mRNA and protein expression in resting skeletal muscle via changes in the Akt1/FOXO/muscle atrophy F-box (MAFbx) and MuRF1 signaling pathway [54]
Summary
The musculoskeletal system is one of the central organ systems in the body. It consists of muscles, tendons, cartilage, ligaments, connective tissues, and nerves. The transfer of electrical signal from the motor neuron to the muscle fiber, which makes the latter contract, is facilitated by neuromuscular junctions. Fast-twitch the fiber, which makes theblood latter since contract, is facilitated neuromuscular junctions They are chemical synapses between a motor neuron and several muscle fibers, like those between regular neurons. Slow-twitch muscle fibers are resilient and mobilized for sustained, prolonged submaximal (aerobic) exercise and postural control. They contain numerous mitochondria and myoglobin and are highly aerobic compared to fast-twitch fibers. They are abundantly supplied with blood since more capillaries surround them. These findings can be concealed by the existence of significant inter-individual responses [6]
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