Melatonin and its Action on Skeletal Muscle

Skeletal muscle disorders are drastically increasing with human aging, incurring enormous healthcare costs and impacting quality of life. Preventive and therapeutic tools to limit the onset and progression of muscle frailty include nutrition and physical training.

Melatonin, the indole produced at night in the pineal and extra-pineal gland, has shown anti-aging, anti-inflammatory, and antioxidant properties. Mitochondria are melatonin's preferred target, which keeps them efficient by eliminating free radicals and reducing oxidative damage.

Dietary melatonin has shown evidence of its efficacy in age-related skeletal muscle disorders in cellular, preclinical, and clinical studies.

Physical activity and adequate nutrition represent the best lifestyle measures to prevent and delay age-related sarcopenia and progressive muscle weakness. Exercise remodels the size and number of skeletal muscle mitochondria and accelerates mitophagy, the peculiar dismantling of damaged mitochondria. Indeed, the proper balance between new mitochondrial synthesis and mitochondrial degradation is dramatically altered in aging skeletal muscles.

The circadian clock conditions whole-body homeostasis and primarily sleep-wake cycles, essential for mental and physical fitness. The direct influence of exercise on endogenous melatonin secretion is still controversial. In any case, exogenous melatonin is useful as an antioxidant and anti-inflammatory nutrient to prolong muscle strength and adaptation during strenuous exercise in rodents and adult men and in aging. In particular, during strenuous training and induced muscle trauma in rodents, melatonin supplementation via different pathways improved muscle recovery, inhibiting NF-kB activation and inflammatory cytokines and decreasing atrophy pathways.

New evidence has been found regarding the gut-muscle axis and the influence of exercise, and probably melatonin on the microbiota. Analysis of intestinal microbiota composition in the elderly demonstrated that there were more pathogens such as Enterobacteriaceae and scarce healthy butyrate-producing bacteria, leading to looser mucosal junctions and altered permeability. Some authors have suggested that gut bacteria may be a potential therapeutic target to alter muscle mass in cancer cachexia or malnutrition and have hypothesized the gut-muscle axis.

This review reinforces the relevance of melatonin as a safe nutraceutical that limits skeletal muscle frailty and prolongs physical performance.

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