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Molecular Regulation of Apoptosis in Fast Plantaris Muscles of Aged Rats

Laboratory of Muscle Biology and Sarcopenia, Division of Exercise Physiology, West Virginia University School of Medicine, Morgantown.

Address correspondence to Stephen E. Alway, PhD, Laboratory of Muscle, Sarcopenia and Muscle Diseases, Division of Exercise Physiology, West Virginia University School of Medicine, Robert C. Byrd Health Science Center, Morgantown, WV 26506-9227. E-mail: salway{at}hsc.wvu.edu

This study tested the hypothesis that aging exacerbates apoptotic signaling in rat fast plantaris muscle during muscle unloading. Plantaris muscle mass was 22% lower in aged animals and the apoptotic index was 600% higher, when compared to those in young adult animals. Following 14 days of hind-limb unloading, absolute plantaris muscle mass was 20% lower in young adult animals with a corresponding 200% higher elevation of the apoptotic index. Unloading had no affect on muscle weight or apoptotic index of aged plantaris muscles. The changes in pro-apoptotic messenger RNA (mRNA) for apoptotic protease activating factor-1 (Apaf-1), Bax, and inhibitor of differentiation protein-2 (Id2) were exacerbated with aging. Bax and Bcl-2 protein levels were also altered differently in aged muscle, compared to young. Significant positive correlations were observed between the changes in Id2 and Bax mRNA, and Id2 and caspase-9 mRNA. These data suggest that a pro-apoptotic environment may contribute to aging-associated atrophy in fast skeletal muscle, but apoptotic signaling differs by age.

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