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 The drug was subsequently withdrawn for 3 months and the muscle mass returned to normal, but the excess cell nuclei persisted.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.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
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
Cites
The effects of supraphysiologic doses of testosterone on muscle size and strength in normal men
Bhasin, S., Storer, T. W., Berman, N., Callegari, C., Clevenger, B., Phillips, J., Bunnell, T. J., Tricker, R., Shirazi, A., & Casaburi, R. (1996) · New England Journal of Medicine · doi:10.1056/nejm199607043350101 · Cited by 1,659
Mechanisms regulating skeletal muscle growth and atrophy
Schiaffino, S., Dyar, K. A., Ciciliot, S., Blaauw, B., & Sandri, M. (2013) · The FEBS Journal · doi:10.1111/febs.12253 · Cited by 1,492
Notch-Mediated Restoration of Regenerative Potential to Aged Muscle
Conboy, I. M., Conboy, M. J., Smythe, G. M., & Rando, T. A. (2003) · Science · doi:10.1126/science.1087573 · Cited by 1,121
Effective fiber hypertrophy in satellite cell-depleted skeletal muscle
McCarthy, J. J., Mula, J., Miyazaki, M., Erfani, R., Garrison, K., Farooqui, A. B., Srikuea, R., Lawson, B. A., Grimes, B., Keller, C., et al. (2011) · Development · doi:10.1242/dev.068858 · Cited by 616
Satellite cells, the engines of muscle repair
Wang, Y. X., & Rudnicki, M. A. (2011) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3265 · Cited by 493
The role of learning and coordination in strength training
Rutherford, O. M., & Jones, D. A. (1986) · European Journal of Applied Physiology · doi:10.1007/bf00422902 · Cited by 484
Lack of myostatin results in excessive muscle growth but impaired force generation
Amthor, H., Macharia, R., Navarrete, R., Schuelke, M., Brown, S., Otto, A., Voït, T., Muntoni, F., Vrbovà, G., Partridge, T. A., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0604893104 · Cited by 438
Staron, R. S., Leonardi, M. J., Karapondo, D. L., Malicky, E. S., Falkel, J. E., Hagerman, F. C., & Hikida, R. S. (1991) · Journal of Applied Physiology · doi:10.1152/jappl.1991.70.2.631 · Cited by 400
Skeletal muscle satellite cells: Changes in proliferation potential as a function of age
Schultz, E., & Lipton, B. H. (1982) · Mechanisms of Ageing and Development · doi:10.1016/0047-6374(82)90105-1 · Cited by 335
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-citationLocalization of muscle gene products in nuclear domains
Pavlath, G. K., Rich, K., Webster, S. G., & Blau, H. M. (1989) · Nature · doi:10.1038/337570a0 · Cited by 326
MAP and kinesin-dependent nuclear positioning is required for skeletal muscle function
Metzger, T. E., Gache, V., Xu, M., Cadot, B., Folker, E. S., Richardson, B. E., Gomes, E. R., & Baylies, M. K. (2012) · Nature · doi:10.1038/nature10914 · Cited by 295
Long-term synapse loss induced by focal blockade of postsynaptlc receptors
Balice‐Gordon, R. J., & Lichtman, J. W. (1994) · Nature · doi:10.1038/372519a0 · Cited by 287
Contribution of satellite cells to IGF‐I induced hypertrophy of skeletal muscle
Barton‐Davis, Shoturma, & Sweeney (1999) · Acta Physiologica Scandinavica · doi:10.1046/j.1365-201x.1999.00618.x · Cited by 283
Aging, stem cells and tissue regeneration: lessons from muscle.
Conboy, I. M., & Rando, T. A. (2005) · Cell Cycle · doi:10.4161/cc.4.3.1518 · Cited by 259
Number and spatial distribution of nuclei in the muscle fibres of normal mice studied in vivo
Bruusgaard, J. C., Liestøl, K., Ekmark, M., Kollstad, K., & Gundersen, K. (2003) · The Journal of Physiology · doi:10.1113/jphysiol.2003.045328 · Cited by 254
Nuclear domains in muscle cells
Hall, Z. W., & Ralston, E. (1989) · Cell · doi:10.1016/0092-8674(89)90597-7 · Cited by 249
Blaauw, B., Canato, M., Agatea, L., Toniolo, L., Mammucari, C., Masiero, E., Abraham, R., Sandri, M., Schiaffino, S., & Reggiani, C. (2009) · The FASEB Journal · doi:10.1096/fj.09-131870 · Cited by 244
Plasticity of myonuclear number in hypertrophied and atrophied mammalian skeletal muscle fibers
Allen, D. L., Monke, S. R., Talmadge, R. J., Roy, R. R., & Edgerton, V. R. (1995) · Journal of Applied Physiology · doi:10.1152/jappl.1995.78.5.1969 · Cited by 240
The Significance of Sarcopenia in Old Age
Dutta, C., & Hadley, E. C. (1995) · The Journals of Gerontology Series A · doi:10.1093/gerona/50a.special_issue.1 · Cited by 228
Muscle hypertrophy driven by myostatin blockade does not require stem/precursor-cell activity
Amthor, H., Otto, A., Vulin, A., Rochat, A., Dumonceaux, J., Garcı́a, L., Mouisel, É., Hourdé, C., Macharia, R., Friedrichs, M., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0811129106 · Cited by 210
Kadi, F. (2008) · British Journal of Pharmacology · doi:10.1038/bjp.2008.118 · Cited by 200
Increase in the number of nuclei and weight in skeletal muscle of rats of various ages
Enesco, M., & Puddy, D. A. (1964) · American Journal of Anatomy · doi:10.1002/aja.1001140204 · Cited by 198
Cellular adaptation of the trapezius muscle in strength-trained athletes
Kadi, F., Eriksson, A., Holmner, S., Butler-Browne, G. S., & Thornell, L. E. (1999) · Histochemistry and Cell Biology · doi:10.1007/s004180050348 · Cited by 189
Moss, F. P. (1968) · American Journal of Anatomy · doi:10.1002/aja.1001220308 · Cited by 183
Alway, S. E., Degens, H., Krishnamurthy, G., & Smith, C. A. (2002) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00598.2001 · Cited by 165
In vivo time-lapse microscopy reveals no loss of murine myonuclei during weeks of muscle atrophy
Bruusgaard, J. C., & Gundersen, K. (2008) · Journal of Clinical Investigation · doi:10.1172/jci34022 · Cited by 162
Jackson, J. R., Mula, J., Kirby, T. J., Fry, C. S., Lee, J. D., Ubele, M. F., Campbell, K. S., McCarthy, J. J., Peterson, C. A., & Dupont‐Versteegden, E. E. (2012) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00207.2012 · Cited by 158
JunB transcription factor maintains skeletal muscle mass and promotes hypertrophy
Raffaello, A., Milan, G., Masiero, E., Carnio, S., Lee, D., Lanfranchi, G., Goldberg, A. L., & Sandri, M. (2010) · Journal of Cell Biology · doi:10.1083/jcb.201001136 · Cited by 156
Modulation of myonuclear number in functionally overloaded and exercised rat plantaris fibers
Roy, R. R., Monke, S. R., Allen, D. L., & Edgerton, V. R. (1999) · Journal of Applied Physiology · doi:10.1152/jappl.1999.87.2.634 · Cited by 154
Skeletal Muscle Cell Mass and Growth: The Concept of the Deoxyribonucleic Acid Unit
Cheek, D. B., Holt, A. B., Hill, D. E., & Talbert, J. L. (1971) · Pediatric Research · doi:10.1203/00006450-197107000-00004 · Cited by 145
Distribution of myonuclei and microtubules in live muscle fibers of young, middle-aged, and old mice
Bruusgaard, J. C., Liestøl, K., & Gundersen, K. (2006) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00913.2005 · Cited by 144
Nuclear domains during muscle atrophy: nuclei lost or paradigm lost?
Gundersen, K., & Bruusgaard, J. C. (2008) · The Journal of Physiology · doi:10.1113/jphysiol.2008.154369 · Cited by 140
Engel, A. G. (1976) · Neurology · doi:10.1212/wnl.26.5.500 · Cited by 138
The fate of newly formed satellite cells during compensatory muscle hypertrophy
Schiaffino, S., Pierobon Bormioli, S., & Aloisi, M. (1976) · Virchows Archiv B Cell Pathology · doi:10.1007/bf02899148 · Cited by 132
Protein Synthesis in Tonic and Phasic Skeletal Muscles
Goldberg, A. L. (1967) · Nature · doi:10.1038/2161219a0 · Cited by 132
Translational musculoskeletal science: Is sarcopenia the next clinical target after osteoporosis?
Matthews, G. D. K., Huang, C. L.-H., Sun, L., & Zaidi, M. (2011) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2011.06236.x · Cited by 127
McCall, G. E., Allen, D. L., Linderman, J. K., Grindeland, R. E., Roy, R. R., Mukku, V. R., & Edgerton, V. R. (1998) · Journal of Applied Physiology · doi:10.1152/jappl.1998.84.4.1407 · Cited by 110
Skeletal muscle morphology in power-lifters with and without anabolic steroids
Eriksson, A., Kadi, F., Malm, C., & Thornell, L. (2005) · Histochemistry and Cell Biology · doi:10.1007/s00418-005-0029-5 · Cited by 110
Dynamic muscle strength alterations to detraining and retraining in elderly men
Taaffe, D. R., & Marcus, R. (1997) · Clinical Physiology · doi:10.1111/j.1365-2281.1997.tb00010.x · Cited by 110
No change in myonuclear number during muscle unloading and reloading
Bruusgaard, J. C., Egner, I. M., Larsen, T. K., Dupre-Aucouturier, S., Desplanches, D., & Gundersen, K. (2012) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00436.2012 · Cited by 107
Denervation effects on myonuclear domain size of rat diaphragm fibers
Aravamudan, B., Mantilla, C. B., Zhan, W., & Sieck, G. C. (2006) · Journal of Applied Physiology · doi:10.1152/japplphysiol.01277.2005 · Cited by 83
Mendias, C. L., Kayupov, E., Bradley, J. R., Brooks, S. V., & Claflin, D. R. (2011) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00126.2011 · Cited by 77
Qaisar, R., Renaud, G., Morine, K., Barton, E. R., Sweeney, H. L., & Larsson, L. (2011) · The FASEB Journal · doi:10.1096/fj.11-192195 · Cited by 68
Pre‐ and postnatal growth and protein turnover in four muscles of the rat
Kelly, F. J., Lewis, S. E. M., Anderson, P., & Goldspink, D. F. (1984) · Muscle & Nerve · doi:10.1002/mus.880070309 · Cited by 67
Čabrić, M., Appell, H.-J., & Resic, A. (1987) · International Journal of Sports Medicine · doi:10.1055/s-2008-1025677 · Cited by 65
Emery–Dreifuss muscular dystrophy
Puckelwartz, M. J., & McNally, E. M. (2011) · Handbook of clinical neurology · doi:10.1016/b978-0-08-045031-5.00012-8 · Cited by 64
Hypoxia inducible factor 1α links fast‐patterned muscle activity and fast muscle phenotype in rats
Lunde, I. G., Anton, S., Bruusgaard, J. C., Rana, Z. A., Ellefsen, S., & Gundersen, K. (2011) · The Journal of Physiology · doi:10.1113/jphysiol.2010.202762 · Cited by 62
Seiden, D. L. (1976) · American Journal of Anatomy · doi:10.1002/aja.1001450405 · Cited by 58
No decrease in myonuclear number after long-term denervation in mature mice
Wada, K., Takahashi, H., Katsuta, S., & Soya, H. (2002) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00025.2002 · Cited by 57
A quantitative study of satellite cells and myonuclei in stretched avian slow tonic muscle
Winchester, P., & Gonyea, W. J. (1992) · The Anatomical Record · doi:10.1002/ar.1092320306 · Cited by 56
Giddings, C. J., & Gonyea, W. J. (1992) · The Anatomical Record · doi:10.1002/ar.1092330203 · Cited by 56
Control of muscle fibre size: a crucial factor in ageing
Hughes, S. M., & Schiaffino, S. (1999) · Acta Physiologica Scandinavica · doi:10.1046/j.1365-201x.1999.00619.x · Cited by 51
Control of muscle fibre size: a crucial factor in ageing.
Hughes, S. M., & Schiaffino, S. (1999) · PubMed · doi:10.1046/j.1365-201x.1999.00622.x · Cited by 50
DNA Injection into Single Cells of Intact Mice
Utvik, J. K., Njå, A., & Gundersen, K. (1999) · Human Gene Therapy · doi:10.1089/10430349950019075 · Cited by 49
Smith, K. M., Winegard, K. J., Hicks, A. L., & McCartney, N. (2003) · Canadian Journal of Applied Physiology · doi:10.1139/h03-034 · Cited by 49
van der Meer, S. F. T., Jaspers, R. T., Jones, D. A., & Degens, H. (2011) · Muscle & Nerve · doi:10.1002/mus.21822 · Cited by 48
Morphometric analyses on the muscles of exercise trained and untrained dogs
Čabrić, M., & James, N. T. (1983) · American Journal of Anatomy · doi:10.1002/aja.1001660309 · Cited by 44
Hypertrophy and proliferation of skeletal muscle fibers from aged quail
Carson, J. A., Yamaguchi, M., & Alway, S. E. (1995) · Journal of Applied Physiology · doi:10.1152/jappl.1995.78.1.293 · Cited by 43
Muscle hypertrophy induced by the Ski protein: cyto‐architecture and ultrastructure
Bruusgaard, J. C., Brack, A. S., Hughes, S. M., & Gundersen, K. (2005) · Acta Physiologica Scandinavica · doi:10.1111/j.1365-201x.2005.01462.x · Cited by 26
L�hrke, H., Hesse, B., & Goerttler, K. (1984) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/bf00402466 · Cited by 9
Flagged first, then by citations
Research works printed but not linked: 2
- 10.1152/ajpcell.00207.2012 · DOI
- Puckelwartz M, 2011, Emery‐Drefuss muscular dystrophy, Handb Clin Neurol, 101, 156
Cited by
Sorted by citations
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review