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. We examine the control of gas exchange, cardiovascular responses, muscle blood flow, and muscle metabolism during exercise. Ageing 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 O2 uptake (VO2 kinetics) which provides information on control mechanisms and the dynamic "coupling" between cardiovascular and muscle metabolic (mitochondrial respiration) adjustments to the energy demands of exercise. An objective of our research is to isolate mechanisms controlling VO2 kinetics and the constraints imposed by O2 delivery and/or utilization. The scientific approach uses breath-by-breath alveolar gas exchange (VO2) coupled with measures of beat-by-beat arterial blood flow by Doppler ultrasound, and near-infrared spectroscopy (NIRS) measures of local muscle oxy/deoxygenation; we have been leaders in using these combined technologies. Also, muscle biopsy and 31P-magnetic resonance spectroscopy are used to measure changes in muscle substrate provision, metabolite contents and enzyme activities. We consistently find VO2 kinetics slowed in older adults, and have shown this to be consequent to a "sluggish" microvascular blood flow (O2 delivery) to the active muscle fibres. Other studies explore potential limitations of oxidative enzyme activation and substrate provision. The objective proposed in this granting cycle is to examine how muscle O2 delivery and (micro)vascular control is influenced by exercise training in older and younger men and women (i.e., age and sex differences), and continue studies of the activation of muscle enzyme and substrate provision in old and young and with exercise training. These studies contribute to our understanding of control of energy provision for physical activity, and provide direction for preventing or reversing age-related changes to the cardiovascular and/or metabolic systems which may contribute to exercise intolerance.