Melatonin, Skeletal Muscle, and the Microbiome: Impacts on Aging, Exercise, and Muscle Health Original paper
Researched by:
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Giorgos Aristotelous
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Giorgos Aristotelous
Read MoreGiorgos — BSc, MSc. Giorgos is an exercise scientist whose training and professional practice sit at the intersection of human performance, clinical health, and emerging microbiome science. He holds a BSc in Sports Science & Physical Education from Aristotle University (2012) and an MSc in Exercise & Health from Democritus University (2016), where his graduate work explored physiological adaptations to training across the lifespan. Now in his 15th year of practice, Giorgos pairs evidence-based coaching (ACSM-CPT, NSCA, USA Weightlifting) with a research-driven interest in how physical activity, body composition, and musculoskeletal integrity shape—and are shaped by—host–microbiome dynamics.
Fact-checked by:
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Karen Pendergrass
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Karen Pendergrass
Read MoreKaren Pendergrass is a microbiome researcher specializing in microbiome-targeted interventions (MBTIs). She systematically analyzes scientific literature to identify microbial patterns, develop hypotheses, and validate interventions. As the founder of the Microbiome Signatures Database, she bridges microbiome research with clinical practice. In 2012, based on her own investigative research, she became the first documented case of FMT for Celiac Disease—four years before the first published case study.
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Giorgos Aristotelous
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Researched by:
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Giorgos Aristotelous
ID
Giorgos Aristotelous
Read More
Fact-checked by:
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Karen Pendergrass
ID
Karen Pendergrass
Read More
Microbiome Signatures identifies and validates condition-specific microbiome shifts and interventions to accelerate clinical translation. Our multidisciplinary team supports clinicians, researchers, and innovators in turning microbiome science into actionable medicine.
Giorgos Aristotelous
What was reviewed?
This review article comprehensively examines the impact of melatonin on skeletal muscle health, exercise performance, and the interplay with the gut–muscle axis, with a particular focus on age-related muscle disorders. The authors synthesize evidence from cellular, animal, and human studies, highlighting melatonin’s multifaceted roles as an antioxidant, anti-inflammatory, and mitochondrial regulator in skeletal muscle. The review also explores how melatonin supplementation may mitigate sarcopenia, muscular atrophy, fibromyalgia, and muscle trauma, while discussing the influence of melatonin on physical activity and recovery. Importantly, the review delves into the emerging understanding of the gut–muscle axis, considering how microbial composition, exercise, and melatonin interact to impact muscle metabolism and function, with implications for microbial biomarkers relevant to a microbiome signatures database.
Who was reviewed?
The review encompasses a broad spectrum of subjects, drawing on data from in vitro studies (muscle cell lines), preclinical animal models (notably rodents, including genetically modified mice and rats), and human clinical studies, both in healthy individuals and those suffering from muscle disorders or aging-associated sarcopenia. The article also summarizes findings from microbiome research, particularly studies utilizing germ-free mice, fecal microbiota transplantation, and human athletes, to illustrate the dynamic interplay between the gut microbiome, muscle physiology, and interventions such as melatonin supplementation and exercise.
Most important findings
Key findings underscore melatonin’s centrality in maintaining skeletal muscle health, especially in the context of aging. Melatonin’s well-established antioxidant and anti-inflammatory effects are complemented by its capacity to preserve mitochondrial function, regulate mitochondrial dynamics (fusion-fission balance), and improve mitophagy, all of which are critical for muscle fiber integrity and function. In both animal and limited human studies, melatonin supplementation protected against age-related muscle degeneration (sarcopenia), improved mitochondrial health, and promoted muscle regeneration post-injury. These benefits extended to fibromyalgia models, where melatonin ameliorated mitochondrial dysfunction and reduced oxidative stress, and to Duchenne muscular dystrophy, where it improved muscle metabolism and strength.
The review highlights the nuanced relationship between melatonin and exercise: melatonin can enhance muscle recovery and antioxidant status post-exercise but its ergogenic effects are variable, depending on dose, timing, and exercise type. Of particular interest to the microbiome field, the article identifies a bidirectional gut–muscle axis. Dysbiosis (especially reduced butyrate-producing bacteria and increased Enterobacteriaceae) is linked to muscle weakness and sarcopenia, while exercise and probiotics beneficially modulate the microbiota, increasing taxa such as Veillonella, Prevotella, and Barnesiella, which correlate with improved muscle performance. Melatonin itself influences the gut microbiota, potentially enhancing beneficial bacteria (e.g., Akkermansia) and restoring microbiota diversity in obese or sleep-deprived animal models.
Key implications
For clinicians, these findings reinforce melatonin’s promise as a safe nutraceutical adjunct in preventing or treating age-related muscle decline and aiding post-injury recovery, particularly in populations at risk for sarcopenia or muscle frailty. Melatonin’s mitochondrial benefits may help sustain muscle strength and metabolic health during aging and chronic disease. The review also underscores the importance of considering the gut microbiome in muscle health, as microbial signatures (such as enrichment of butyrate producers or specific taxa like Veillonella) may serve as biomarkers for muscle function and targets for intervention. However, clinical translation is limited by a paucity of large-scale human studies, variability in melatonin dosing regimens, and the need for better characterization of microbiome–muscle interactions in humans. Future research should clarify optimal melatonin dosing, its effects in diverse patient populations, and the mechanistic underpinnings of the gut–muscle–melatonin axis.