Efficacy of myonuclear addition may explain differential myofiber growth among resistance-trained young and older men and women

Petrella, John K.; Kim, Jeong-su; Cross, James M.; Kosek, David J.; Bamman, Marcas M.

doi:10.1152/ajpendo.00190.2006

Cited by 356Muscle Physiology and DisordersMuscle metabolism and nutritionSports Performance and Training

Efficacy of myonuclear addition may explain differential myofiber growth among resistance-trained young and older men and women

Petrella, John K., Kim, Jeong-su, Cross, James M., Kosek, David J., Bamman, Marcas M.·2006·American Journal of Physiology-Endocrinology and Metabolism

DOI 10.1152/ajpendo.00190.2006

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Abstract

Skeletal muscle stem (satellite) cells supporting growth/regeneration are thought to be activated and incorporated into growing myofibers by both endocrine and locally expressed autocrine/paracrine growth factors, the latter being load sensitive. We recently found that myofiber hypertrophy with resistance training is superior in young men (YM) vs. young women and older adults (Kosek DJ, Kim JS, Petrella JK, Cross JM, and Bamman MM. J Appl Physiol 101: 531-544, 2006). We hypothesized that the advanced myofiber hypertrophy in YM is facilitated by myonuclear addition in response to a milieu promoting stem cell activation. Twenty-six young (27.0 +/- 1 yr, 50% women) and 26 older (63.7 +/- 1 yr, 50% women) adults completed 16 wk of knee extensor resistance training. Vastus lateralis biopsies were obtained at baseline, 24 h after one bout, and after 16 wk. Muscle stem cells were identified immunohistochemically with anti-neural cell adhesion molecule (NCAM+). Muscle transcript levels of IGF-I and mechanogrowth factor (MGF) were determined by RT-PCR. Serum IGF-I, IGF-binding protein (IGFBP)-3, IGFBP-1, total and free testosterone, sex hormone-binding globulin (SHBG), and androstenedione were assessed by radioimmunoassay. Myofiber hypertrophy was twofold greater in YM vs. others, and only YM increased NCAM+ cells per 100 myofibers (49%) and myonuclei per fiber (19%) (P < 0.05). IGF-IEa mRNA was higher in young and increased acutely (29%) with summation by 16 wk (96%) (P < 0.05). MGF mRNA increased only in young after one bout (81%) and by 16 wk (85%) (P < 0.001). Circulating IGF-I was twofold higher in young, whereas IGFBP-1 was lowest in YM (P < 0.05). Among men, free testosterone was 59% higher in YM (P < 0.01). Myonuclear addition was most effectively accomplished in YM, which likely drove the superior growth.

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Following activation, proliferation, and fusion, Pax7+ satellite cells donate new myonuclei to the syncytium, expanding the transcriptional and nucleolar infrastructure available to support continued adaptation.
“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 [66]
Under conditions where pre-existing nuclear capacity becomes limiting, further expansion of ribosome biogenesis and protein synthetic infrastructure may depend, at least in part, on the incorporation of additional myonuclei.
“further expansion of ribosome biogenesis and protein synthetic infrastructure may depend, at least in part, on the incorporation of additional myonuclei”
From Ribosome Biogenesis as a Putative Bottleneck to Skeletal Muscle Hypertrophy: Mechanisms, Human Evidence, and Practical Modulators (2026) · cites this paper as [66]
Once initial gains supported by existing myonuclei are largely realized, further adaptation may require a slower phase of structural remodeling involving satellite cell participation and myonuclear expansion.
“Once the initial gains supported by existing myonuclei have been largely realized, further adaptation may require a slower phase of structural remodeling involving satellite cell participation and myonuclear expansion [66,68].”
From Ribosome Biogenesis as a Putative Bottleneck to Skeletal Muscle Hypertrophy: Mechanisms, Human Evidence, and Practical Modulators (2026) · cites this paper as [66]
Because new myonuclei donate new nucleoli to the syncytium, satellite cell activation aligns with the requirement to expand the architectural space available for ribosome biogenesis.
“Because new myonuclei donate new nucleoli to the syncytium, this finding aligns with the requirement to physically expand the architectural space available for ribosome biogenesis [66,96].”
From Ribosome Biogenesis as a Putative Bottleneck to Skeletal Muscle Hypertrophy: Mechanisms, Human Evidence, and Practical Modulators (2026) · cites this paper as [66]
Extreme hypertrophic responders exhibited a high capability for satellite cell activation and myonuclear addition compared to non-responders.
“Early investigations into these responder clusters, spearheaded by Petrella et al., demonstrated that extreme hypertrophic responders exhibited a high capability for satellite cell activation and myonuclear addition compared to non-responders [66].”
From Ribosome Biogenesis as a Putative Bottleneck to Skeletal Muscle Hypertrophy: Mechanisms, Human Evidence, and Practical Modulators (2026) · cites this paper as [66]

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Satellite cell and myonuclear accretion is related to training-induced skeletal muscle fiber hypertrophy in young males and females
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Authors: Petrella, J. K., Kim, J.-S., Cross, J. M., Kosek, D. J., & Bamman, M. M.
Affiliations: University of Alabama at Birmingham (US)
ORCID: Cross, James M.
Bamman, Marcas M.
Venue: American Journal of Physiology-Endocrinology and Metabolism
Publisher: American Physiological Society
Published: 2006-11
Volume: 291
Issue: 5
Pages: E937-E946
ISSN: 0193-1849 (ISSN-L)
1522-1555
DOI: 10.1152/ajpendo.00190.2006
OpenAlex: W2154326737
Cited by: 356
References: 61
Citations by year: 2026: 4 · 2025: 5 · 2024: 8 · 2023: 15 · 2022: 24 · 2021: 15 · 2020: 18 · 2019: 22 · 2018: 24 · 2017: 17 · 2016: 28 · 2015: 22 · 2014: 20 · 2013: 16 · 2012: 25
FWCI: 6.65
Type: journal article
Language: en
Open access: closed
Locations: American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
PubMed (publishedVersion)
Funders: U.S. Department of Veterans Affairs
University of Alabama at Birmingham
National Institute on Aging (R01AG017896, R01 AG17896)
National Center for Research Resources (M01RR00032, M01RR000032)
NIH Clinical Center
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
Health Sciences › Medicine › Orthopedics and Sports Medicine › Sports Performance and Training
Keywords: muscle fiber hypertrophy, resistance training, skeletal muscle stem cells, satellite cells, insulin-like growth factor I, IGFBP-1, IGFBP-3, free testosterone, sex differences, aging, vastus lateralis, CD56, androstenedione, sex hormone-binding globulin
MeSH terms: Adult, Aged, Aging, Androstenedione, Cell Nucleus, Female, Humans, Insulin-Like Growth Factor I, Male, Middle Aged, RNA, Messenger, Sex Characteristics, Sex Hormone-Binding Globulin, Testosterone, Exercise, Muscle, Skeletal, Insulin-Like Growth Factor Binding Protein 1, Insulin-Like Growth Factor Binding Protein 3, Neural Cell Adhesion Molecules, Satellite Cells, Skeletal Muscle, Cell Size

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Efficacy of myonuclear addition may explain differential myofiber growth among resistance-trained young and older men and women

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