Acute and chronic contractile activity-induced adaptations in muscle and mitochondrial function

Exercise training is a potent stimulus for favourable phenotypic adaptations in muscle, including the induction of mitochondrial biogenesis. Although the occurrence of organelle expansion in response to chronic muscle use is accepted, the cellular events governing this remodeling are undefined. Thus, the purpose of this dissertation was to examine the acute and chronic contractile activity-induced adaptations in skeletal muscle and mitochondrial function in young and old animals. The intracellular signals associated with contractile activity are important for the induction of downstream phenotypic plasticity. In study 1, we investigated the influence of muscle oxygen consumption and reactive oxygen species (ROS) production on kinase signaling. The results demonstrate that mitochondrial content influenced the rate of ROS production in resting muscle. Furthermore, several protein kinases were differentially sensitive to increments in oxygen consumption, and this sensitivity was also related to the muscle mitochondrial volume. In study 2, we further explored the effect of mitochondrial content on the acute contraction-induced kinase signaling in skeletal muscle. We found that mitochondrial content was inversely related to kinase activation in resting skeletal muscle. Moreover, training-induced increases in mitochondrial volume were associated with an attenuated adaptive signaling response subsequent to a single bout of contractions, suggesting a mitochondrially mediated mechanism regulating training-elicited muscle remodeling. The aim of study 3 was to examine the effect of age on the acute exercise-induced signaling response. Skeletal muscle from old animals exhibited pathophysiological properties, including reduced force production, fatigue resistance, mitochondrial content, and ATP-synthesizing ability, all characteristic of aging-associated sarcopenia. This condition was correlated with an attenuated signaling response to acute exercise, which was dependent on muscle mitochondrial content. Study 4 assessed the adaptive plasticity of mitochondria in young and old animals after chronic muscle use. We found that the mitochondria from aged animals were able to adapt favourably to a period of chronic contractile activity, despite an attenuated signaling response after each individual bout of exercise. However, the adaptive plasticity of aged animals was lower than that observed in young animals. These findings underscore the importance of daily physical activity in the maintenance and improvement of health for individuals of all ages.