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Efficacy of myonuclear addition may explain differential myofiber growth among resistance-trained young and older men and women
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, 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]
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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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Metadata
- Authors
- Petrella, J. K., Kim, J.-S., Cross, J. M., Kosek, D. J., & Bamman, M. M.
- Affiliations
- University of Alabama at Birmingham (US)
- 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
- 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
- Health Sciences › Nursing › Nutrition and Dietetics › 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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