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Constantin-Teodosiu, T. Molecular Mechanisms of Muscle Fatigue. Encyclopedia. Available online: (accessed on 01 December 2023).
Constantin-Teodosiu T. Molecular Mechanisms of Muscle Fatigue. Encyclopedia. Available at: Accessed December 01, 2023.
Constantin-Teodosiu, Tim. "Molecular Mechanisms of Muscle Fatigue" Encyclopedia, (accessed December 01, 2023).
Constantin-Teodosiu, T.(2021, November 25). Molecular Mechanisms of Muscle Fatigue. In Encyclopedia.
Constantin-Teodosiu, Tim. "Molecular Mechanisms of Muscle Fatigue." Encyclopedia. Web. 25 November, 2021.
Molecular Mechanisms of Muscle Fatigue

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. 

neuroinflammation skeletal muscle atrophy muscle function fatigue

1. Muscle Architecture

The musculoskeletal system is one of the central organ systems in the body. It consists of muscles, tendons, cartilage, ligaments, connective tissues, and nerves.
There are three main types of muscle tissue: skeletal, cardiac, and smooth [1]. Skeletal muscles are fibrous tissues found in humans or animals mainly attached by tendons to the skeleton’s bones. They can contract/shorten upon neuro-mediated calcium stimulation, thereby moving the whole body while maintaining the position of parts of the body.
A skeletal muscle is made up of multiple fascicles, and each one includes numerous muscle fibers (Figure 1, [2]). The muscle fibers are, in turn, composed of myofibrils. The myofibrils are composed of overlapping, protein-made, thick (myosin) and thin (actin) myofilaments highly organized as sarcomere units, which are de facto the contractile units of the muscle. The sheaths made of connective tissue that encapsulate the bundle of myofibrils, muscle fibers, and the outer side of the muscle are named endomysium, perimysium, and epimysium, respectively.
Figure 1. Muscle organization (A. Bonetta and LF Bonewald, originally adapted from Servier Medical Art— accessed on 1 October 2021) [2].


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