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

Abstract

Petrella JK, Kim J, Mayhew DL, Cross JM, Bamman MM. Potent myofiber hypertrophy during resistance training in humans is associated with satellite cell-mediated myonuclear addition: a cluster analysis. J Appl Physiol 104: 1736-1742, 2008. First published April 24, 2008 doi:10.1152/japplphysiol.01215.2007.-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 ϭ 17), modest (Mod, n ϭ 32), or nonresponders (Non, n ϭ 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][2233][2234][2235][2236][2237][2238][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 Ͻ 0.01) than both Mod and Non, suggesting superior basal myogenic potential. SC number increased robustly during training in Xtr only (117%; P Ͻ 0.001). Myonuclear addition occurred in Mod (9%; P Ͻ 0.05) and was most effectively accomplished in Xtr (26%; P Ͻ 0.001). After training, Xtr had more myonuclei per fiber than Non (23%; P Ͻ 0.05) and tended to have more than Mod (19%; P ϭ 0.056). Both Xtr and Mod expanded the myonuclear domain to meet (Mod) or exceed (Xtr) 2,000 m 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. strength training; skeletal muscle; neural cell adhesion molecule; myonucleus; myogenesis EACH MYONUCLEUS WITHIN THE multinucleated skeletal myofiber regulates gene transcription and subsequent protein synthesis over a finite volume of cytoplasm (6,7,23). This volume per nucleus, or myonuclear domain, is not a fixed quantity as evidenced during atrophy due to disuse (3, 24) or aging (25) as loss of cell volume exceeds nuclear shedding. Similarly, our laboratory and others have shown that some initial myofiber hypertrophy can expand the cytoplasmic volume associated with each myonucleus (17,25). This has led some to debate whether the addition of nuclei is required for skeletal myofiber hypertrophy (23). However, a ceiling size on the domain has been suggested (17, 23, 25) based on the concept that sufficient expansion of the myonuclear domain likely puts each nucleus under greater strain to supply the necessary gene products, driving a demand for the a...

β-Hydroxy-β-Methylbutyrate Did Not Enhance High Intensity Resistance Training-Induced Improvements in Myofiber Dimensions and Myogenic Capacity in Aged Female Rats

“…The percent increases in satellite cell and myonuclear content in the present study corresponded well to our previous work in which satellite cell and myonuclei number increased by 117% and 26%, respectively, in humans that demonstrated robust RTinduced hypertrophy (Petrella et al, 2008). The extensive expansion of the satellite cell population in response to RT has been suggested to represent a reservoir that has accumulated in anticipation of future mechanical stimuli (Petrella et al, 2008). It may also reflect an improved ability to maintain myofiber integrity or support growth with advancing age.…”

Blunted hypertrophic response in old mouse muscle is associated with a lower satellite cell density and is not alleviated by resveratrol

“…3 to a training program also had the largest accretion of new myonuclei and the highest number of SCs per myofiber before training (Petrella et al, 2008). This suggests that not only an age-related decline in SC number (Chakkalakal et al, 2012), but also impaired proliferation and/or differentiation may underlie the blunted hypertrophic response in old age.…”

Heterogeneity in resistance training-induced muscle strength and mass responses in men and women of different ages

“…In previous studies with healthy human subjects, e.g., several genetic variations (Riechman et al 2004;Devaney et al 2009;Walsh et al 2012;Van Deveire et al 2012), differences in skeletal muscle gene Raue et al 2012;Phillips et al 2013) and microRNA expression (Davidsen et al 2011), phosphorylation status of signaling proteins (Mayhew et al 2011;Mitchell et al 2013), androgen receptor concentrations (Ahtiainen et al 2011;Mitchell et al 2013), and satellite cell count (Petrella et al 2008) have been suggested to segregate high and low responders to RTinduced muscle hypertrophy. The physiological aspects of individual variation in phenotype responses to RT are apparently very complex phenomena and more studies specifically focused on high and low responders are required to reveal unambiguously the mechanisms of individual differences in RT-induced adaptations.…”