Relative rDNA copy number is not associated with resistance training-induced skeletal muscle hypertrophy and does not affect myotube anabolism in vitro

Ribosomal DNA (rDNA) copies are organized in tandem repeats across multiple chromosomes, and inter-individual variation in rDNA copy number has been speculated to be a modifier of the hypertrophic responses to resistance training. In the current study, 82 apparently healthy participants (n=53 males, 21{+/-}1 years old; n=29 females, 21{+/-}2 years old) performed 10-12 weeks of supervised full-body resistance training. Whole-body, mid-thigh, and histological skeletal muscle hypertrophy outcomes were determined, as was relative rDNA copy number from pre-intervention vastus lateralis (VL) biopsies. Pre- and post-intervention VL biopsy mRNA/rRNA markers of ribosome content and biogenesis were assayed in all participants, and these targets were also assayed in the 29 females 24 hours following their first workout bout. Across all 82 participants, no significant associations were evident between relative rDNA copy number and training-induced changes in whole body lean mass (r = -0.034, p=0.764), vastus lateralis thickness (r = 0.093, p=0.408), mean myofiber cross-sectional area (r = -0.128, p=0.259), or changes in muscle RNA concentrations (r = 0.026, p=0.818). Several significant, positive associations in females support ribosome biogenesis being linked to training-induced myofiber hypertrophy. Follow-up studies using LHCN-M2 myotubes demonstrate a reduction in relative rDNA copy number induced by bisphenol A (BPA). However, BPA did not significantly affect myotube diameter or prevent insulin-like-growth factor-induced hypertrophy. These findings provide strong evidence that relative rDNA copy number is not associated with myofiber anabolism and provide further mechanistic evidence for ribosome biogenesis being involved in this phenomenon.