Physiological regulation linked with physical activity and health

The developed and developing world is ageing, getting fatter, and becoming less physically active. As a result there is a pandemic of diseases associated with physiological ‘dysregulation,’ especially as it relates to cardiovascular and metabolic function. High levels of habitual physical activity and exercise are remarkably protective against these diseases, and these topics were the focus of The Journal of Physiology Symposium ‘Physiological regulation linked with physical activity and health’, held at the 2009 IUPS meeting in Kyoto, Japan. The goal of the symposium was to review, understand and frame these broad issues in the context of physiological regulation in humans. The symposium was well attended and played to a full house in a large lecture room.

The overall tone of the symposium was set by Frank Booth, who detailed the complex and integrative health benefits of exercise and physical activity (Booth & Laye, 2009). Dr Booth highlighted the limitations of looking at pharmacological interventions that activate a single biological pathway and over drawing parallels to exercise. He also raised important questions about what the normal physiological state is and argued that since animals have evolved over millions of years to be physically active, the physically active state is the appropriate biological control condition. In this context, there are a number of animal models of metabolic disease, including transgenic animals, where the disease phenotype is only seen in cage-confined animals without access to voluntary exercise wheels. So the whole question of what is normal is open for debate.

As noted above, physical activity and exercise have profound effects on the cardiovascular system. Doug Seals reviewed evidence showing that the normal changes in vascular stiffness that occur with ageing are largely absent in humans who are either habitually physically active or who exercise train (Seals et al. 2009). The role of endothelial dysfunction, nitric oxide bioavailability, and oxidative stress in the age-related deterioration of vascular function in inactive humans and animals was contrasted to the augmented or preserved function in the active state.

Mike Joyner presented data on the impact of physical activity and exercise on overall cardiovascular risk (Joyner & Green, 2009). The key observation is that the positive effects of physical activity and exercise on cardiovascular morbidity and mortality are much greater than would be predicted on the basis of changes in so-called traditional risk factors. The idea advanced was that improved endothelial function and improved autonomic function, acting alone and in combination, are largely responsible for the ‘missing’ risk reduction.

In the last 10 or so years an important idea that has emerged is that contracting skeletal muscles release substances (myokines) that have a host of positive effects on metabolic and cardiovascular function. These appear to either set the physiological stage for the anti-diabetic, anti-inflammatory, and anti-obesity effects of exercise or be directly responsible for them. The leader in this field has been Bente Pedersen who reviewed her work and that of her collaborators and identified new areas for investigation (Pedersen, 2009). In this context, there has been a search for an ‘exercise factor’ released from skeletal muscle that had distant effects on other physiological systems for many years, and Dr Pedersen and her team have identified a number of exercise factors.

Hiroshi Nose presented data from his group's studies, which include thousands of middle-age and older humans performing high-intensity interval walking training in Nagano Prefecture, Japan (Nose et al. 2009). This study is important because it demonstrates that it is possible to do large-scale, high-resolution phenotyping and ask mechanistic physiological questions in a community setting. It also shows that high-intensity exercise can have a profound effect on physiological regulation in older humans, especially in the least fit. Finally, the Nagano study is important because it demonstrates how information technology and other data management systems can be used to generate community-based public health-oriented exercise interventions and also facilitate mechanistic physiology studies at the same time.

A major question in integrative physiology research is how genes and genetic variation influence physiological responses and adaptations in humans. Masayuki Mori and colleagues have evaluated key human gene polymorphisms and how they might influence physiological responses and adaptations to exercise training in humans (Mori et al. 2009). They have used the unique Nagano cohort described above and shown that only a small fraction of the adaptive responses could be explained on the basis of common genetic variants. This is good news from a public health perspective because it suggests that almost all humans are trainable and will reap the benefits of increased physical activity.

Much of the focus of the symposium dealt with physiological responses in older humans and how they adapt to exercise training and how exercise training and physical activity are protective. One area of increased health risk for older humans is environmental heat stress associated with heat waves. In younger humans, thermoregulatory adaptations to exercise can improve heat tolerance via changes in sweating, skin blood flow, and longer-term adaptations in plasma volume. Some of these adaptations clearly occur in older humans as well, but Kazunobu Okazaki demonstrated that for the increased plasma volume to occur in older subjects, dietary protein supplementation after exercise was essential (Okazaki et al. 2009). This observation adds to earlier findings in older humans about post-exercise protein consumption and the preservation of skeletal muscle mass. It also highlights the synergistic roles of nutrition and physical activity with ageing.

George Brooks reviewed his 30+ year metabolic odyssey related to lactic acid and how ideas related to lactate metabolism have shifted from an oversimplified view that it was an ‘evil humour’ associated with hypoxia and anoxia (Brooks, 2009). In reality, lactate is a key metabolic intermediary with a number of important regulatory roles. Its metabolism is also influenced by exercise training, and in the context of the overall symposium, one is tempted to ask what are the age-related changes in lactate metabolism and how are they influenced by physical activity? Do age-related or physical inactivity related changes in the physiology of lactate contribute to metabolic dysregulation in older humans? These are clearly questions for the future.

In summary, ‘Physiological regulation linked with physical activity and health’ presented information operating from the level of genes and signalling pathways to populations. Most provocatively perhaps we all need to think about what constitutes ‘normal’ physiological regulation in the context of the questions raised by Frank Booth.