A Pediatric Clinical Center for Molecular Transducers of Physical Activity (MoTrPAC): Towards a Molecular Map of Exercise in the Pediatric Origins of Health Across the Lifespan

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A Pediatric Clinical Center for Molecular Transducers of Physical Activity (MoTrPAC): Towards a Molecular Map of Exercise in the Pediatric Origins of Health Across the Lifespan The goals of this research are to: 1) map the molecular mechanisms through which exercise benefits health in children and adolescents, a critical period of change in the human phenotype, and 2) provide the MoTrPAC consortium with rigorously collected and reproducible data from exercise studies in children and adolescents. This proposal is based on exciting discoveries in a range of disciplines, including: 1) new insights into age- dependent progression of gene expression during growth in children, 2) emerging data highlighting the central role played by leukocytes (n.b., an accessible tissue in child health research) in transducing exercise into health benefits, 3) pilot data showing remarkable interaction between the molecular transducers of growth and the molecular transducers of exercise, and 4) novel approaches to measuring and understanding physiologic and morphometric responses to acute and chronic exercise in children. In the proposed acute exercise studies, the immediate physiologic, proteomic, metabolomic, and leukocyte function and transcriptomic response to a brief exercise-induced perturbation in cellular homeostasis will be measured in a cross section of early- and late-pubertal boys and girls. In the proposed chronic exercise studies (a 12-week, prospective, aerobic exercise training intervention), we will compare the magnitude of the biomarker and molecular adaptation to training, along with the accompanying morphometric and physiologic changes between early- and late-pubertal girls and boys. The combined data from the acute and chronic exercise studies will be analyzed with systems- computational techniques to map the networks that transduce physical activity to health in the growing child and adolescent. Because phenotype is a “moving target” during growth, we will use accurate methodologies (such as DXA for body composition and breath-by-breath gas exchange for cardiopulmonary exercise testing) that have proven in our hands to be feasible in large numbers of children and adolescents. Traditional exercise testing will be complemented by laboratory-based “real-life” exercise protocols, and in all cases, scaled to each participant’s physical fitness, estimates of habitual physical activity, noninvasive measures of vascular health, and training volume and mode. In this way, the pediatric and adult data will be readily integrated. As an academic health center unit devoted uniquely to the study of physical activity and health in children in a very diverse region, our group is exceptionally qualified to contribute to the MoTrPAC consortium. We 1) published a series of discoveries of novel genomic and epigenetic exercise biomarkers in circulating leukocytes in both children and adults, 2) performed thousands of pediatric exercise tests, 3) conducted many successful prospective exercise training interventions in early and late pubertal children, and 4) were leaders in Project HEALTHY, the large NIH multicenter study to prevent obesity and type 2 diabetes in children, published in the New England Journal of Medicine. This research will ultimately enable child health professionals, families, and community leaders to optimize the use of exercise to promote health during a critical period of growth.