Potent myofiber hypertrophy during resistance training in humans is associated with satellite cell-mediated myonuclear addition: a cluster analysis

J Appl Physiol (1985). 2008 Jun;104(6):1736-42. doi: 10.1152/japplphysiol.01215.2007. Epub 2008 Apr 24.


A present debate in muscle biology is whether myonuclear addition is required during skeletal muscle hypertrophy. We utilized K-means cluster analysis to classify 66 humans after 16 wk of knee extensor resistance training as extreme (Xtr, n = 17), modest (Mod, n = 32), or nonresponders (Non, n = 17) based on myofiber hypertrophy, which averaged 58, 28, and 0%, respectively (Bamman MM, Petrella JK, Kim JS, Mayhew DL, Cross JM. J Appl Physiol 102: 2232-2239, 2007). We hypothesized that robust hypertrophy seen in Xtr was driven by superior satellite cell (SC) activation and myonuclear addition. Vastus lateralis biopsies were obtained at baseline and week 16. SCs were identified immunohistochemically by surface expression of neural cell adhesion molecule. At baseline, myofiber size did not differ among clusters; however, the SC population was greater in Xtr (P < 0.01) than both Mod and Non, suggesting superior basal myogenic potential. SC number increased robustly during training in Xtr only (117%; P < 0.001). Myonuclear addition occurred in Mod (9%; P < 0.05) and was most effectively accomplished in Xtr (26%; P < 0.001). After training, Xtr had more myonuclei per fiber than Non (23%; P < 0.05) and tended to have more than Mod (19%; P = 0.056). Both Xtr and Mod expanded the myonuclear domain to meet (Mod) or exceed (Xtr) 2,000 mum(2) per nucleus, possibly driving demand for myonuclear addition to support myofiber expansion. These findings strongly suggest myonuclear addition via SC recruitment may be required to achieve substantial myofiber hypertrophy in humans. Individuals with a greater basal presence of SCs demonstrated, with training, a remarkable ability to expand the SC pool, incorporate new nuclei, and achieve robust growth.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Cell Proliferation*
  • Cluster Analysis*
  • Cohort Studies
  • Exercise*
  • Humans
  • Hypertrophy
  • Insulin-Like Growth Factor Binding Protein 1 / blood
  • Insulin-Like Growth Factor Binding Protein 3
  • Insulin-Like Growth Factor Binding Proteins / blood
  • Insulin-Like Growth Factor I / analysis
  • Middle Aged
  • Muscle Contraction*
  • Muscle Fibers, Skeletal / pathology*
  • Neural Cell Adhesion Molecules / analysis
  • Phenotype
  • Quadriceps Muscle / chemistry
  • Quadriceps Muscle / pathology*
  • Quadriceps Muscle / physiopathology
  • Satellite Cells, Skeletal Muscle / chemistry
  • Satellite Cells, Skeletal Muscle / pathology*


  • IGFBP1 protein, human
  • IGFBP3 protein, human
  • Insulin-Like Growth Factor Binding Protein 1
  • Insulin-Like Growth Factor Binding Protein 3
  • Insulin-Like Growth Factor Binding Proteins
  • Neural Cell Adhesion Molecules
  • Insulin-Like Growth Factor I