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Circadian Rhythms, the Molecular Clock, and Skeletal Muscle
Open accessAbstract
Circadian rhythms are the approximate 24-h biological cycles that function to prepare an organism for daily environmental changes. They are driven by the molecular clock, a transcriptional:translational feedback mechanism that in mammals involves the core clock genes Bmal1, Clock, Per1/2, and Cry1/2. The molecular clock is present in virtually all cells of an organism. The central clock in the suprachiasmatic nucleus (SCN) has been well studied, but the clocks in the peripheral tissues, such as heart and skeletal muscle, have just begun to be investigated. Skeletal muscle is one of the largest organs in the body, comprising approximately 45% of total body mass. More than 2300 genes in skeletal muscle are expressed in a circadian pattern, and these genes participate in a wide range of functions, including myogenesis, transcription, and metabolism. The circadian rhythms of skeletal muscle can be entrained both indirectly through light input to the SCN and directly through time of feeding and activity. It is critical for the skeletal muscle molecular clock not only to be entrained to the environment but also to be in synchrony with rhythms of other tissues. When circadian rhythms are disrupted, the observed effects on skeletal muscle include fiber-type shifts, altered sarcomeric structure, reduced mitochondrial respiration, and impaired muscle function. Furthermore, there are detrimental effects on metabolic health, including impaired glucose tolerance and insulin sensitivity, which skeletal muscle likely contributes to considering it is a key metabolic tissue. These data indicate a critical role for skeletal muscle circadian rhythms for both muscle and systems health. Future research is needed to determine the mechanisms of molecular clock function in skeletal muscle, identify the means by which skeletal muscle entrainment occurs, and provide a stringent comparison of circadian gene expression across the diverse tissue system of skeletal muscle.
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“Circadian clocks exist in virtually all cells in the body including skeletal muscles and is a ubiquitous mechanism that functions to temporarily regulate certain metabolic and cell physiologic processes (Harfmann et al., 2015).”
From Myosteatosis in the Context of Skeletal Muscle Function Deficit: An Interdisciplinary Workshop at the National Institute on Aging (2020) · cites this paper as Harfmann et al., 2015
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Metadata
- Authors
- Harfmann, B. D., Schroder, E. A., & Esser, K. A.
- Affiliations
- University of Kentucky (US)
- Corresponding author
- Esser, Karyn A.
- Venue
- Journal of Biological Rhythms
- Publisher
- SAGE Publications
- Published
- 2014-12-15
- Volume
- 30
- Issue
- 2
- Pages
- 84-94
- ISSN
- 0748-7304 (ISSN-L)
- 1552-4531
- PMC
- PMC4470613
- OpenAlex
- W2166609167
- Cited by
- 211
- References
- 234
- Citations by year
- 2026: 21 · 2025: 18 · 2024: 19 · 2023: 20 · 2022: 26 · 2021: 17 · 2020: 29 · 2019: 15 · 2018: 11 · 2017: 14 · 2016: 13 · 2015: 7
- FWCI
- 1.28
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Biological Rhythms (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- University of Kentucky
- National Institutes of Health
- National Institute of Environmental Health Sciences (RC1ES018636)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR066082, AR066082, R01AR055246)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and Work-Related Fatigue
- Keywords
- circadian rhythm, molecular clock, skeletal muscle, clock genes, Bmal1, clocks, suprachiasmatic nucleus, circadian entrainment, meal timing, circadian gene expression, muscle fiber type shift, mitochondrial respiration, glucose tolerance, insulin sensitivity, muscle metabolism
- MeSH terms
- Animals, Circadian Rhythm, Gene Expression Regulation, Humans, Mutation, Suprachiasmatic Nucleus, Muscle, Skeletal, Mice, CLOCK Proteins, Circadian Clocks
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