Time- and exercise-dependent gene regulation in human skeletal muscle
Open accessAbstract
BACKGROUND: Skeletal muscle remodeling is a critical component of an organism's response to environmental changes. Exercise causes structural changes in muscle and can induce phase shifts in circadian rhythms, fluctuations in physiology and behavior with a period of around 24 hours that are maintained by a core clock mechanism. Both exercise-induced remodeling and circadian rhythms rely on the transcriptional regulation of key genes. RESULTS: We used DNA microarrays to determine the effects of resistance exercise (RE) on gene regulation in biopsy samples of human quadriceps muscle obtained 6 and 18 hours after an acute bout of isotonic exercise with one leg. We also profiled diurnal gene regulation at the same time points (2000 and 0800 hours) in the non-exercised leg. Comparison of our results with published circadian gene profiles in mice identified 44 putative genes that were regulated in a circadian fashion. We then used quantitative PCR to validate the circadian expression of selected gene orthologs in mouse skeletal muscle. CONCLUSIONS: The coordinated regulation of the circadian clock genes Cry1, Per2, and Bmal1 6 hours after RE and diurnal genes 18 hours after RE in the exercised leg suggest that RE may directly modulate circadian rhythms in human skeletal muscle.
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The same detrimental metabolic changes that occur in response to circadian misalignment and altered expression of clock genes may also be ameliorated by performing exercise.
“Furthermore, the same detrimental metabolic changes that occur in response to circadian misalignment and altered expression of clock genes may also be ameliorated by performing exercise [20,31,32].”
From Exercise mitigates sleep-loss-induced changes in glucose tolerance, mitochondrial function, sarcoplasmic protein synthesis, and diurnal rhythms (2021) · cites this paper as [32]
Others have reported exercise-induced changes in skeletal muscle clock gene expression, which is thought to be a time-of-day dependent effect.
“While others have reported exercise-induced changes in skeletal muscle clock gene expression [32,66], this is thought to be a time-of-day dependent effect [66].”
From Exercise mitigates sleep-loss-induced changes in glucose tolerance, mitochondrial function, sarcoplasmic protein synthesis, and diurnal rhythms (2021) · cites this paper as [32]
The molecular clock is functional within human muscles.
“These results are consistent with the human data reported from two timepoints by Zambon et al. (2003) and demonstrate that the molecular clock is functional within human muscles (Perrin et al., 2018).”
From Myosteatosis in the Context of Skeletal Muscle Function Deficit: An Interdisciplinary Workshop at the National Institute on Aging (2020) · cites this paper as Zambon et al., 2003
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- Authors
- Zambon, A. C., McDearmon, E. L., Salomonis, N., Vranizan, K. M., Johansen, K. L., Adey, D., Takahashi, J. S., Schambelan, M., & Conklin, B. R.
- Affiliations
- University of California, San Francisco (US)
- Northwestern University (US)
- Corresponding author
- Conklin, Bruce R
- ORCID
- Venue
- Genome Biology
- Published
- 2003-09-25
- Volume
- 4
- Issue
- 10
- Pages
- R61-R61
- ISSN
- 1465-6906 (ISSN-L)
- 1474-760X
- PMC
- PMC328450
- OpenAlex
- W2099496913
- Cited by
- 254
- References
- 55
- Citations by year
- 2026: 5 · 2025: 17 · 2024: 19 · 2023: 18 · 2022: 19 · 2021: 8 · 2020: 21 · 2019: 9 · 2018: 8 · 2017: 6 · 2016: 13 · 2015: 9 · 2014: 10 · 2013: 10 · 2012: 7
- FWCI
- 2.26
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Genome biology (publishedVersion)
- PubMed Central (publishedVersion, other-oa)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- Gladstone Institutes
- National Institutes of Health (2m01rr000083-41)
- National Heart, Lung, and Blood Institute (R01HL060664, HL60664, HL-66621, U01HL066621, HL61689, R01HL061689)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 07418, T32DK007418)
- National Center for Research Resources (M01-RR000083, RR 00083)
- 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
- Health Sciences › Medicine › Rehabilitation › Exercise and Physiological Responses
- Keywords
- resistance training, skeletal muscle remodeling, circadian rhythm, clock genes, gene expression profiling, CRY1, Per2, Bmal1, diurnal gene expression, quadriceps, human skeletal muscle
- MeSH terms
- Animals, Biopsy, Circadian Rhythm, Gene Expression Regulation, Humans, Interleukin-1, Isotonic Contraction, Time Factors, Signal Transduction, Exercise, Cluster Analysis, Muscle, Skeletal, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Mice, Rats
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