title: Ribosome biogenesis may augment resistance training-induced myofiber hypertrophy and is required for myotube growth in vitro.
abstract: Resistance exercise training (RT) is the most effective method for increasing skeletal muscle mass in older adults; however, the amount of RT-induced muscle growth is highly variable between individuals. Recent evidence from our laboratory and others suggests ribosome biogenesis may be an important factor regulating RT-induced hypertrophy, and we hypothesized that the extent of hypertrophy is at least partly regulated by the amount of RT-induced ribosome biogenesis. To examine this, 42 older adults underwent 4 wk of RT aimed at inducing hypertrophy of the knee extensors (e.g., 2 sets of squat, leg press, and knee extension, 10-12 repetition maximums, 3 days/wk), and vastus lateralis muscle biopsies were performed pre- and post-RT. Post hoc K-means cluster analysis revealed distinct differences in type II myofiber hypertrophy among subjects. The percent change in type II myofiber size in nonresponders (Non; n = 17) was -7%, moderate responders (Mod; n = 19) +22%, and extreme responders (Xtr; n = 6) +83%. Total muscle RNA increased only in Mod (+9%, P < 0.08) and Xtr (+26%, P < 0.01), and only Xtr increased rRNA content (+40%, P < 0.05) and myonuclei/type II fiber (+32%, P < 0.01). Additionally, Mod and Xtr had a greater increase in c-Myc protein levels compared with Non (e.g., approximately +350 and +250% vs. +50%, respectively, P < 0.05). In vitro studies showed that growth factor-induced human myotube hypertrophy is abolished when rRNA synthesis is knocked down using the Pol I-specific inhibitor CX-5461. Overall, these data implicate ribosome biogenesis as a key process regulating the extent of RT-induced myofiber hypertrophy in older adults.
authors: Department of Cell, Developmental, and Integrative Biology, University of Alabama at Birmingham, Birmingham, Alabama.|UAB Center for Exercise Medicine, University of Alabama at Birmingham, Birmingham, Alabama; and.
authors: Michael J
authors: MJ
authors: Stec
authors: Department of Cell, Developmental, and Integrative Biology, University of Alabama at Birmingham, Birmingham, Alabama.|UAB Center for Exercise Medicine, University of Alabama at Birmingham, Birmingham, Alabama; and.
authors: Neil A
authors: NA
authors: Kelly
authors: Department of Cell, Developmental, and Integrative Biology, University of Alabama at Birmingham, Birmingham, Alabama.|UAB Center for Exercise Medicine, University of Alabama at Birmingham, Birmingham, Alabama; and.
authors: Gina M
authors: GM
authors: Many
authors: UAB Center for Exercise Medicine, University of Alabama at Birmingham, Birmingham, Alabama; and.|Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama; and.
authors: Samuel T
authors: ST
authors: Windham
authors: Department of Cell, Developmental, and Integrative Biology, University of Alabama at Birmingham, Birmingham, Alabama.|UAB Center for Exercise Medicine, University of Alabama at Birmingham, Birmingham, Alabama; and.
authors: S Craig
authors: SC
authors: Tuggle
authors: Department of Cell, Developmental, and Integrative Biology, University of Alabama at Birmingham, Birmingham, Alabama; mbamman@uab.edu.|UAB Center for Exercise Medicine, University of Alabama at Birmingham, Birmingham, Alabama; and.|Geriatric Research, Education, and Clinical Center, Veterans Affairs Medical Center, Birmingham, Alabama.
authors: Marcas M
authors: MM
authors: Bamman
mesh_terms: D000328:Adult; D000368:Aged; D052160:Benzothiazoles / Q000494:pharmacology; D016000:Cluster Analysis; D005260:Female; D006801:Humans; D006984:Hypertrophy; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D018656:Muscle Fibers, Fast-Twitch / Q000378:metabolism; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000254:growth & development / Q000378:metabolism; D009287:Naphthyridines / Q000494:pharmacology; D001678:Organelle Biogenesis; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D052097:Quadriceps Muscle / Q000254:growth & development* / Q000378:metabolism; D012313:RNA / Q000378:metabolism; D012318:RNA Polymerase I / Q000037:antagonists & inhibitors; D012335:RNA, Ribosomal / Q000187:drug effects / Q000378:metabolism*; D055070:Resistance Training; D012270:Ribosomes / Q000378:metabolism*
chemical_list: D052160:Benzothiazoles; C557717:CX 5461; C489427:MYC protein, human; D009287:Naphthyridines; D016271:Proto-Oncogene Proteins c-myc; D012335:RNA, Ribosomal; D012313:RNA; D012318:RNA Polymerase I
keywords: Pol I; c-Myc; rRNA; ribosome; skeletal muscle