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

我们的研究是人类系统层面的综合生理学。我们研究了运动过程中对气体交换、心血管反应、肌肉血流和肌肉代谢的控制。衰老被用来说明这些系统的可塑性，老年人提供了一个模型来辨别心血管控制因素，调节气体交换和肌肉代谢，以及运动反应中的限制因素。我们研究的一个主题是我们对氧气摄取（VO2动力学）调节的时间过程的研究，它提供了控制机制和心血管和肌肉代谢（线粒体呼吸）调节运动能量需求之间的动态“耦合”的信息。我们的研究目标是分离控制VO2动力学的机制以及O2输送和/或利用所施加的限制。科学方法使用呼吸肺泡气体交换（VO2），通过多普勒超声测量动脉血流，以及近红外光谱（NIRS）测量局部肌肉氧/脱氧；我们在使用这些综合技术方面一直处于领先地位。此外，肌肉活检和31p磁共振波谱法用于测量肌肉底物供应、代谢物含量和酶活性的变化。我们一直发现老年人的VO2动力学减慢，并且已经表明这是由于微血管血流（氧气输送）“缓慢”到活跃的肌肉纤维。其他研究探索了氧化酶激活和底物提供的潜在局限性。在这个给予周期中提出的目标是检查运动训练如何影响老年和年轻男性和女性的肌肉O2输送和（微）血管控制（即年龄和性别差异），并继续研究老年人和年轻人以及运动训练中肌肉酶和底物供应的激活。这些研究有助于我们理解身体活动能量供应的控制，并为预防或逆转心血管和/或代谢系统的年龄相关变化提供方向，这些变化可能导致运动不耐受。

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.