Modulating Human Skeletal Muscle with Loading and Unloading

Abstract

Skeletal muscle is central to human movement, metabolism, and health. Loading and unloading are the addition and removal, respectively, of mechanical stimuli from muscle. Loading muscle with resistance training (RT) – contraction against external resistance – can lead to muscle hypertrophy, and RT prescription (RTx) involves several modifiable variables that can modulate adaptations to RT. Unloading muscle with immobilization can lead to muscle atrophy, and nutritional interventions might mitigate unfavourable adaptations to immobilization. The purpose of this thesis was to advance our understanding of factors that modulate skeletal muscle adaptations to loading and unloading in healthy adults; specifically, RTx in the context of loading and nutrition in the context of unloading. This thesis contributes unprecedented evidence for new and existing RT prescriptions, demonstrating the extensive variety of RT prescriptions that increase muscle size and function. Moreover, these discoveries are incorporated into updated RTx guidelines for a world-leading organization. In the first clinical trial to administer the natural post-biotic Urolithin A during immobilization, a nutritional beverage with Urolithin A did not mitigate immobilization-induced reductions in mitochondrial content, muscle size, muscle protein synthesis, and muscle function. This thesis advances our knowledge of how RTx and nutrition modulate muscle with loading and unloading by contributing the most comprehensive evidence syntheses on RTx, evidence-based RTx guidelines, and clinical data on the effect of a novel nutritional intervention during immobilization. This thesis has several potential implications in practice, policy, education, and research.