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      Impact of Melatonin on Skeletal Muscle and Exercise

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          Abstract

          Skeletal muscle disorders are dramatically increasing with human aging with enormous sanitary costs and impact on the quality of life. Preventive and therapeutic tools to limit onset and progression of muscle frailty include nutrition and physical training. Melatonin, the indole produced at nighttime in pineal and extra-pineal sites in mammalians, has recognized anti-aging, anti-inflammatory, and anti-oxidant properties. Mitochondria are the favorite target of melatonin, which maintains them efficiently, scavenging free radicals and reducing oxidative damage. Here, we discuss the most recent evidence of dietary melatonin efficacy in age-related skeletal muscle disorders in cellular, preclinical, and clinical studies. Furthermore, we analyze the emerging impact of melatonin on physical activity. Finally, we consider the newest evidence of the gut–muscle axis and the influence of exercise and probably melatonin on the microbiota. In our opinion, this review reinforces the relevance of melatonin as a safe nutraceutical that limits skeletal muscle frailty and prolongs physical performance.

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          Most cited references184

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          Skeletal muscle: a brief review of structure and function.

          Skeletal muscle is one of the most dynamic and plastic tissues of the human body. In humans, skeletal muscle comprises approximately 40% of total body weight and contains 50-75% of all body proteins. In general, muscle mass depends on the balance between protein synthesis and degradation and both processes are sensitive to factors such as nutritional status, hormonal balance, physical activity/exercise, and injury or disease, among others. In this review, we discuss the various domains of muscle structure and function including its cytoskeletal architecture, excitation-contraction coupling, energy metabolism, and force and power generation. We will limit the discussion to human skeletal muscle and emphasize recent scientific literature on single muscle fibers.
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            Suprachiasmatic nucleus: cell autonomy and network properties.

            The suprachiasmatic nucleus (SCN) is the primary circadian pacemaker in mammals. Individual SCN neurons in dispersed culture can generate independent circadian oscillations of clock gene expression and neuronal firing. However, SCN rhythmicity depends on sufficient membrane depolarization and levels of intracellular calcium and cAMP. In the intact SCN, cellular oscillations are synchronized and reinforced by rhythmic synaptic input from other cells, resulting in a reproducible topographic pattern of distinct phases and amplitudes specified by SCN circuit organization. The SCN network synchronizes its component cellular oscillators, reinforces their oscillations, responds to light input by altering their phase distribution, increases their robustness to genetic perturbations, and enhances their precision. Thus, even though individual SCN neurons can be cell-autonomous circadian oscillators, neuronal network properties are integral to normal function of the SCN.
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              Extrapineal melatonin: sources, regulation, and potential functions.

              Endogenous melatonin is synthesized from tryptophan via 5-hydroxytryptamine. It is considered an indoleamine from a biochemical point of view because the melatonin molecule contains a substituted indolic ring with an amino group. The circadian production of melatonin by the pineal gland explains its chronobiotic influence on organismal activity, including the endocrine and non-endocrine rhythms. Other functions of melatonin, including its antioxidant and anti-inflammatory properties, its genomic effects, and its capacity to modulate mitochondrial homeostasis, are linked to the redox status of cells and tissues. With the aid of specific melatonin antibodies, the presence of melatonin has been detected in multiple extrapineal tissues including the brain, retina, lens, cochlea, Harderian gland, airway epithelium, skin, gastrointestinal tract, liver, kidney, thyroid, pancreas, thymus, spleen, immune system cells, carotid body, reproductive tract, and endothelial cells. In most of these tissues, the melatonin-synthesizing enzymes have been identified. Melatonin is present in essentially all biological fluids including cerebrospinal fluid, saliva, bile, synovial fluid, amniotic fluid, and breast milk. In several of these fluids, melatonin concentrations exceed those in the blood. The importance of the continual availability of melatonin at the cellular level is important for its physiological regulation of cell homeostasis, and may be relevant to its therapeutic applications. Because of this, it is essential to compile information related to its peripheral production and regulation of this ubiquitously acting indoleamine. Thus, this review emphasizes the presence of melatonin in extrapineal organs, tissues, and fluids of mammals including humans.
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                Author and article information

                Journal
                Cells
                Cells
                cells
                Cells
                MDPI
                2073-4409
                24 January 2020
                February 2020
                : 9
                : 2
                : 288
                Affiliations
                [1 ]Anatomy and Physiopathology Division, Department of Clinical and Experimental Sciences, University of Brescia, Viale Europa 11, 25123 Brescia, Italy; gaia.favero@ 123456unibs.it (G.F.); luigi.rodella@ 123456unibs.it (L.F.R.)
                [2 ]Interdepartmental University Center of Research “Adaptation and Regeneration of Tissues and Organs (ARTO)”, University of Brescia, 25123 Brescia, Italy
                Author notes
                [* ]Correspondence: alessandra.stacchiotti@ 123456unibs.it ; Tel.: +39-030-3717478; Fax: +39-030-3717486
                Author information
                https://orcid.org/0000-0002-6767-6617
                https://orcid.org/0000-0001-6895-7106
                Article
                cells-09-00288
                10.3390/cells9020288
                7072499
                31991655
                7b744f21-d67b-4ea5-a6b7-a97184cf203f
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 12 December 2019
                : 22 January 2020
                Categories
                Review

                melatonin,sarcopenia,fibromyalgia,physical training,mitochondria,mitophagy,aging,rodents

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