THE EFFECTS OF AGE, SARCOPENIA, AND RESISTANCE EXERCISE TRAINING ON MITOCHONDRIAL STRUCTURAL DYNAMICS IN SKELETAL MUSCLE

Abstract

Sarcopenia, the progressive, age-related loss of skeletal muscle mass, contributes to older adults’ risk of falls, hospitalization, and loss of independence. Mitochondrial dysfunction is a hallmark trait of aging and sarcopenia that may be mediated by changes to mitochondrial structure and location through the involvement of mitochondrial fusion, fission, and mitophagy (collectively referred to as mitochondrial quality control). Therefore, the purpose of this dissertation was to investigate whether mitochondrial quality control is altered by age or sarcopenia. The first study performed in a rat model of aging demonstrated that expression of proteins regulating fusion and mitophagy was higher in skeletal and cardiac muscle from old vs. young rats, and this was accompanied by reduced expression of fission proteins in skeletal muscle in the old rats. The second study included older humans and revealed no differences in mitochondrial quality control protein expression in skeletal muscle from sarcopenic vs. non-sarcopenic older adults. Furthermore, twelve weeks of resistance exercise training did not alter the expression of mitochondrial quality control proteins in the sarcopenic individuals. The third study investigated morphological differences in mitochondrial subpopulations and lipid droplets from the sarcopenic individuals from study two, both before and after resistance exercise training. Peripherally located and intermyofibrillar mitochondrial content and morphology did not change significantly after resistance exercise training. Lipid droplets from the intermyofibrillar region were similarly unchanged, but lipid droplets from the peripheral region had minor morphological changes after resistance exercise training. Together, this dissertation indicates that mitochondrial quality control proteins in skeletal and cardiac muscle are altered in response to aging and may contribute to mitochondrial dysfunction, but mitochondrial structural dynamics in skeletal muscle do not appear to be altered in older adults with a moderate degree of sarcopenia. This suggests that other, non-mitochondrial factors may play larger roles in the pathophysiology of sarcopenia. While the sarcopenic participants did improve muscular strength after resistance training, this was not accompanied by changes in mitochondrial content, morphology, or quality control. Therefore, resistance exercise training may not be an effective strategy to enhance mitochondrial structural dynamics in sarcopenia.