The DOI matches its Crossref record; 61 of the 61 references it cites were found in a registry or an index.
A cellular memory mechanism aids overload hypertrophy in muscle long after an episodic exposure to anabolic steroids
Open accessAbstract
Key points Training studio folklore suggests that previous strength training, with or without the use of anabolic steroids facilitates re‐acquisition of muscle mass even after long intervening periods of inactivity. This ‘muscle memory’ has previously been attributed to motor learning, but our data suggest the existence of a cellular memory residing in the muscle fibres themselves. Muscle fibres have multiple nuclei, and the number of nuclei increases when muscle mass increases. When mice were briefly treated with steroids the muscle mass and number of nuclei increased. The drug was subsequently withdrawn for 3 months and the muscle mass returned to normal, but the excess cell nuclei persisted. When such muscles were subjected to overload they grew by 30% over 6 days while controls grew insignificantly. Our data suggest that previous strength training might be beneficial later in life, and that a brief exposure to anabolic steroids might have long lasting performance‐enhancing effects. Abstract Previous strength training with or without the use of anabolic steroids facilitates subsequent re‐acquisition of muscle mass even after long intervening periods of inactivity. Based on in vivo and ex vivo microscopy we here propose a cellular memory mechanism residing in the muscle cells. Female mice were treated with testosterone propionate for 14 days, inducing a 66% increase in the number of myonuclei and a 77% increase in fibre cross‐sectional area. Three weeks after removing the drug, fibre size was decreased to the same level as in sham treated animals, but the number of nuclei remained elevated for at least 3 months (>10% of the mouse lifespan). At this time, when the myonuclei‐rich muscles were exposed to overload‐exercise for 6 days, the fibre cross‐sectional area increased by 31% while control muscles did not grow significantly. We suggest that the lasting, elevated number of myonuclei constitutes a cellular memory facilitating subsequent muscle overload hypertrophy. Our findings might have consequences for the exclusion time of doping offenders. Since the ability to generate new myonuclei is impaired in the elderly our data also invites speculation that it might be beneficial to perform strength training when young in order to benefit in senescence.
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In the citing paper
“Following activation, proliferation, and fusion, Pax7+ satellite cells donate new myonuclei to the syncytium, thereby expanding the transcriptional and nucleolar infrastructure available to support continued adaptation [25,66,67].”
From Ribosome Biogenesis as a Putative Bottleneck to Skeletal Muscle Hypertrophy: Mechanisms, Human Evidence, and Practical Modulators (2026) · cites this paper as [67]
In the citing paper
“Importantly, nuclei acquired during training may persist during subsequent unloading, contributing to the cellular basis of muscle memory and facilitating a more rapid re-expansion of translational capacity during retraining [67,69]”
From Ribosome Biogenesis as a Putative Bottleneck to Skeletal Muscle Hypertrophy: Mechanisms, Human Evidence, and Practical Modulators (2026) · cites this paper as [67]
In the citing paper
“In female mice, short-term treatment with testosterone increased both muscle fibre cross-sectional area (CSA) and myonuclei number [79].”
From Integrating Transwomen and Female Athletes with Differences of Sex Development (DSD) into Elite Competition: The FIMS 2021 Consensus Statement (2021) · cites this paper as [79]
In the citing paper
“Research shows that in addition to hormone concentrations, the number of myonuclei can affect skeletal muscle training [79, 80].”
From Integrating Transwomen and Female Athletes with Differences of Sex Development (DSD) into Elite Competition: The FIMS 2021 Consensus Statement (2021) · cites this paper as [79]
In the citing paper
“After cessation of exposure, muscle fibre CSA reverted to that of the control arm, but the number of myonuclei remained 42% higher than controls for at least 3 months.”
From Integrating Transwomen and Female Athletes with Differences of Sex Development (DSD) into Elite Competition: The FIMS 2021 Consensus Statement (2021) · cites this paper as [79]
In the citing paper
“These resident myonuclei facilitated enhanced muscle hypertrophy during 6-day resistance training overload (31% increase in the fibre CSA vs. 6% in controls); this increase remained 20% higher compared with controls after 14-day overload [79].”
From Integrating Transwomen and Female Athletes with Differences of Sex Development (DSD) into Elite Competition: The FIMS 2021 Consensus Statement (2021) · cites this paper as [79]
Citations
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Myonuclei acquired by overload exercise precede hypertrophy and are not lost on detraining
Bruusgaard, J. C., Johansen, I. B., Egner, I. M., Rana, Z. A., & Gundersen, K. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0913935107 · Cited by 327
Self-citation
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Cited by
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Human skeletal muscle possesses an epigenetic memory of hypertrophy
Seaborne, R. A., Strauss, J., Cocks, M., Shepherd, S., O’Brien, T. D., van Someren, K. A., Bell, P. G., Murgatroyd, C., Morton, J. P., Stewart, C. E., et al. (2018) · Scientific Reports · doi:10.1038/s41598-018-20287-3 · Cited by 334
Egan, B., & Sharples, A. P. (2023) · Physiological Reviews · doi:10.1152/physrev.00054.2021 · Cited by 278
HUNTER, S. K., S. ANGADI, S., BHARGAVA, A., HARPER, J., HIRSCHBERG, A. L., D. LEVINE, B., L. MOREAU, K., J. NOKOFF, N., STACHENFELD, N. S., & BERMON, S. (2023) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0000000000003300 · Cited by 241
The molecular athlete: exercise physiology from mechanisms to medals
Furrer, R., Hawley, J. A., & Handschin, C. (2023) · Physiological Reviews · doi:10.1152/physrev.00017.2022 · Cited by 253
Muscle metabolism and atrophy: let’s talk about sex
Rosa-Caldwell, M. E., & Greene, N. P. (2019) · Biology of Sex Differences · doi:10.1186/s13293-019-0257-3 · Cited by 202
Metadata
- Authors
- Egner, I. M., Bruusgaard, J. C., Eftestøl, E., & Gundersen, K.
- Affiliations
- University of Oslo (NO)
- Venue
- The Journal of Physiology
- Publisher
- Wiley
- Published
- 2013-11-22
- Volume
- 591
- Issue
- 24
- Pages
- 6221-6230
- ISSN
- 0022-3751 (ISSN-L)
- 1469-7793
- PMC
- PMC3892473
- OpenAlex
- W2107574257
- Cited by
- 159
- References
- 61
- Citations by year
- 2026: 10 · 2025: 13 · 2024: 10 · 2023: 13 · 2022: 13 · 2021: 28 · 2020: 12 · 2019: 15 · 2018: 13 · 2017: 5 · 2016: 9 · 2015: 9 · 2014: 7 · 2013: 1
- FWCI
- 3.88
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Journal of Physiology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Norges Forskningsråd
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Nursing › Nutrition and Dietetics › Muscle metabolism and nutrition
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Keywords
- muscle memory, myonuclei, anabolic steroids, testosterone propionate, muscle hypertrophy, muscle fiber cross-sectional area, resistance training, doping, aging, motor learning
- MeSH terms
- Animals, Cell Nucleus, Physical Exertion, Female, Hypertrophy, Testosterone, Muscle Fibers, Skeletal, Mice
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