Understanding the impact of lifespan changes in respiratory muscle function

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Human respiratory muscles fulfill an important life-sustaining function: breathing. Their highly coordinated contractions generate airflow through the lungs and airways (i.e., ventilation) to ensure the adequate delivery of oxygen and elimination of carbon dioxide. During exercise, active muscles increase the requirements for oxygen and the production of carbon dioxide, which necessitates a corresponding increase in ventilation. The increase in ventilation that occurs during exercise is often considerable and must be performed by the respiratory muscles, which comes at a substantial energetic and neuromuscular cost. However, our understanding of how human respiratory muscles function is incomplete. Most notably, aging is a fundamental biological process that affects almost all human tissues, including skeletal muscles, but its impact on the respiratory muscles remains unclear. Given their vital role within the human body, understanding how the action of the respiratory muscles is coordinated and fuelled, and how this changes over the course of the human lifespan is of critical importance. The long--term objective of my research is to evaluate the relationship between the structure and function of human respiratory muscles and how they respond to physiological challenges, such as exercise. Over the next five years, my short--term objective is to determine how human respiratory muscle function changes across the lifespan and how this might impact the physiological response to exercise by addressing three separate, but interrelated, aims: Aim 1 - understand how aging influences respiratory muscle energetics, Aim 2 - determine how respiratory muscle work influences the fatigue of the respiratory muscle during exercise, and Aim 3 - determine if the lifespan changes in respiratory muscle function can be altered by targeted training of the respiratory musculature. My research program will utilize an integrative approach that considers the interaction between the respiratory, cardiovascular, nervous, and muscular systems in order to better understand how the respiratory muscles function. Experiments will involve detailed measurements and manipulation of respiratory muscle oxygen consumption, mechanical efficiency, and neuromuscular function during isolated respiratory muscle work or whole-body exercise. Overall, my research program seeks to improve our understanding of how the respiratory muscles influence the physiological response to exercise, which is important and relevant to biologists studying human physiology. Furthermore, my program will provide important training opportunities for undergraduate and graduate trainees by teaching them tangible skills and involving them in every aspect of research process.