Regulation of gas exchange and metabolism in exercise, system limits and age-related modulation

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Our research is in integrative physiology at the systems level in humans. Our research programme examines the control and interrelationship amongst gas exchange, cardiovascular responses, muscle blood flow, muscle microvascular oxygenation, and muscle metabolism during exercise. Our `ageing' model is used to illustrate the plasticity of these systems, and older adults provide a model to discern cardiovascular control factors, regulation of gas exchange and muscle metabolism, and limiting factors in the exercise response. A theme in our research is our studies of the time course of adjustment of pulmonary O2 uptake (VO2P kinetics) which provides information on control mechanisms and the dynamic `coupling' between cardiovascular and muscle O2 utilization (mitochondrial respiration) adjustments to the energy demands of exercise. An objective of our research is to identify mechanisms controlling VO2 kinetics and the constraints imposed by O2 delivery and/or O2 utilization. The scientific approach uses breath-by-breath alveolar gas exchange coupled with measures of beat-by-beat conduit artery blood flow by Doppler ultrasound, near-infrared spectroscopy (NIRS) measures of local muscle microvascular oxy/deoxygenation, and biopsy sampling of muscle tissue during exercise transients to measure changes in muscle substrate provision, metabolite content and enzyme activities. We are unique in combining both non-invasive and invasive measures into our research programme, and we are recognized nationally and internationally for our studies on VO2p `kinetics'. We consistently report slower VO2P (and muscle blood flow and O2 delivery) kinetics i) in healthy old vs young adults, ii) in less fit, untrained individuals, iii) in exercise transitions from a high vs low baseline metabolic rate, iv) consequent to induction of a hyperventilation-induced hypocapnic alkalosis, and v) after consuming high fat vs high carbohydrate diets, which implicates both O2 dependent and independent mechanisms contributing to the regulation of mitochondrial energy production. With this grant cycle we plan to examine relationships amongst VO2P kinetics and muscle O2 utilization, blood flow and O2 delivery, and muscle metabolism and mitochondrial respiration kinetics in young and older adults. We also plan to examine the relationships amongst VO2P and exercise training, muscle substrate availability (through dietary intervention), baseline metabolic rate, and time course of change in endothelial function and blood flow adjustment consequent to exercise training. These studies contribute to our understanding of control of energy provision for physical activity, and provide direction for preventing and reversing age-related changes to the cardiovascular and/or metabolic systems which may contribute to exercise intolerance.**