The Protective Effect of Melatonin Against Age-Associated, Sarcopenia-Dependent Tubular Aggregate Formation, Lactate Depletion, and Mitochondrial Changes

Abstract

To gain insight into the mechanism of sarcopenia and the protective effect of melatonin, the gastrocnemius muscles of young (3-4 months), early-aged (12 months), and old-aged (24 months) wild-type C57BL/6J female mice were examined by magnetic resonance and microscopy. Locomotor activity, lactate production, and nuclear apoptosis were also assessed. The results support the early onset of sarcopenia at 12 months of age, with reduction of muscle fiber number, muscle weight/body weight ratio, lactate, and locomotor activity. Lipid droplet infiltration and autophagosomes were also detected. These changes driven little effects on the early-aged muscle, but they got worse in old-aged animals by the progressive damage of the muscle. Old-aged muscle showed a reduction of the mitochondrial number, a destruction of the mitochondrial cristae, and swelling. Tubular aggregates and nucleic acid fragmentation were the most striking findings in old-aged muscle, reflecting a broad damage with loss of autophagy efficacy. Oral melatonin administration conserved the normal muscular architecture, weight, muscle fiber number, and activity in the old age; it stimulated lactate production, prevented mitochondrial damage and tubular aggregates, and reduced the percentage of apoptotic nuclei in aged muscles. Altogether, gastrocnemius muscle showed age-mediated signs of sarcopenia that were reduced by melatonin treatment.

Impact of Melatonin on Skeletal Muscle and Exercise

“…Furthermore, inflammation and lower glycolytic potential, assessed as lactate amount, strongly influenced skeletal muscle metabolism in sarcopenia [89]. In the gastrocnemius muscle of aged mice altered autophagy, nuclear fragmentation and abnormal lactate production were detected, but all these adverse changes decreased by oral melatonin intake [90]. Remarkably, melatonin supplementation in NLRP3 KO mice was particularly beneficial to retard the onset of sarcopenia in gastrocnemius muscle in aged animals [91].…”

Lack of retinoid acid receptor-related orphan receptor alpha accelerates and melatonin supplementation prevents testicular aging

“…Previous studies on testis reported the protective effects of melatonin on reduction of non-enzymatic lipid oxidation of rat testicular mitochondria and microsomes [ 43 ], reduction of irradiation-induced damage of rat testes [ 44 ], treatment of oxidative testicular damage induced by 2-bromopropane through its ROS scavenger and antiapoptotic effect [ 45 ], minimizing the testicular ischemic injury of rats’ cellular organelles by preserving the DNA against oxidative damage [ 46 ], reducing of germ cell apoptosis and cadmium-induced cellular stress in testes [ 47 ], alleviation of testicular damage and attenuation of germ cell apoptosis in hyperlipidemic mice [ 48 ], removing the cigar smoke-induced testicular injury and restoring normal testicular tissue [ 49 ]. Melatonin dose of 10 mg/kg used in this study has also revealed significant anti-aging beneficial effects in SAM and wild-type mice [ 24 , 26 , 50 ]. Furthermore, therapeutic doses of the melatonin ranging from 5 mg to 50 mg/kg bw were previously reported [ 51 ].…”

Modulatory Role of Melatonin on the Structure of Hard Palatal Mucosa of Aged Rats

“…The current study findings proved the anti-oxidant potential of melatonin, which was reported previously in many researches. These studies reported that melatonin modulated apoptotic proteins, hence reducing apoptosis [ 4] , improved vascular endothelial function [ 5] , resulted in efficient elimination of ROS and nitric oxide [ 6] , and provided protection against age-related mitochondrial dysfunction [ 7] . All of these miraculous effects of melatonin were welldisplayed in the current study, in the form of reduced apoptotic activity, enhanced cellular proliferation, enhanced vascularization, reduced inflammatory cells in CT, enhanced new collagen production, and diminished collagen destruction or hyalinization.…”

“…Subgroup II.b: Animals in this subgroup received Melatonin via gastric gavage at a dose of 10mg/kg/day dissolved in 1 ml of distilled water, for eight consecutive weeks [ 7] .…”

“…Melatonin is a potent antioxidant with proven anti-inflammatory functions. Numerous in vitro and in vivo studies have documented the ability of melatonin to protect against free radical-induced tissue damage [6][7][8] . Hence, this study presents a histological and immuno-histochemical evaluation of the modulatory effect of melatonin on various structural elements of the hard-palatal mucosa in aged rats in comparison with young adult rats.…”