All ETDs from UAB

Advisory Committee Chair

Marcas M Bamman

Advisory Committee Members

Christopher S Bickel

Louis J Dell'Italia

Stuart J Frank

Joanne Murphy-Ullrich

Document Type

Dissertation

Date of Award

2015

Degree Name by School

Doctor of Philosophy (PhD) Heersink School of Medicine

Abstract

Numerous chronic medical conditions, as well as normal aging result in a significant loss of skeletal muscle mass. This has profound effects on quality of life and can increase the risk of all-cause mortality. Currently, the most potent treatment for reversing the loss of muscle mass is resistance exercise training (RT); however, the human muscle fiber growth (hypertrophy) response to this treatment is quite variable, and older adults do not respond as favorably to this treatment as younger adults. The focus of this dissertation is to elucidate the role that ribosome biogenesis plays in regulating the RT-induced hypertrophic response. We show that markers of ribosome biogenesis are attenuated in older adult muscle following an acute, single bout of resistance exercise, indicating a possible mechanism regulating the age-induced blunted hypertrophic response to RT. Additionally, using a K-means cluster analysis, we show that those older individuals with a successful hypertrophic response to a standardized RT program significantly increase muscle rRNA production, and that this is associated with a marked induction of c-Myc expression following RT. A small minority of older individuals with the most extreme hypertrophic response also increase the number of myonuclei per myofiber following RT, likely to provide more rDNA template for rRNA transcription. Finally, we show that chemical inhibition of de novo Pol I-mediated rRNA transcription completely abolishes growth factor-induced increases in protein synthesis and myotube hypertrophy in vitro. Previously, it was thought that increased translational efficiency was the primary regulator of RT-induced muscle hypertrophy. The data presented here suggest that ribosome biogenesis is a novel regulatory mechanism that controls RT-induced human skeletal muscle growth.

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