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

身体活动分子传感器儿科临床中心（MoTrPAC）：走向 运动的分子图谱在整个生命周期的健康的儿科起源 本研究的目标是：1）绘制运动有益于健康的分子机制， 儿童和青少年，人类表型变化的关键时期，和2）提供MoTrPAC 这些数据来自于儿童和青少年运动研究中严格收集和可重复的数据。 这项建议是基于一系列学科的令人兴奋的发现，包括：1）对年龄的新见解- 儿童生长过程中基因表达的依赖性进展，2）新出现的数据突出了 白细胞所起的作用（N.B.，在儿童健康研究中， 健康益处，3）试验数据显示生长的分子换能器之间的显著相互作用， 运动的分子传感器，以及4）测量和理解生理学的新方法 以及儿童对急性和慢性运动的形态测量反应。在拟议的急性运动研究中， 直接的生理，蛋白质组，代谢组，白细胞功能和转录组反应， 运动引起的细胞内稳态的短暂扰动将在早期和晚期的横截面中测量。 青春期后期的男孩和女孩。在拟议的慢性运动研究（12周，前瞻性，有氧运动， 运动训练干预），我们将比较生物标志物和分子适应的大小， 沿着青春期早期和晚期的形态和生理变化 女孩和男孩。急性和慢性运动研究的综合数据将通过系统进行分析- 计算技术，以映射网络，身体活动，以健康的成长中的孩子 和青春期。由于表型是生长过程中的“移动目标”，我们将使用准确的方法学 (such作为身体成分的DXA和心肺运动测试的逐呼吸气体交换） 在我们手中已经证明是可行的，在大量的儿童和青少年。传统运动 测试将由基于实验室的“现实生活”锻炼方案来补充，并且在所有情况下，都按比例缩放到每个 参与者的身体健康，习惯性体力活动的估计，血管健康的非侵入性测量， 以及训练量和训练方式。通过这种方式，儿童和成人数据将很容易整合。作为 学术健康中心单位专门致力于身体活动和健康的儿童在一个非常研究 我们的团队在不同的地区，非常有资格为MoTrPAC联盟做出贡献。1）出版 在两个国家的循环白细胞中发现了一系列新型基因组和表观遗传运动生物标志物 儿童和成人，2）进行了数千次儿科运动试验，3）进行了许多成功的 在青春期早期和晚期儿童中进行前瞻性运动训练干预，以及4）是项目的领导者 健康，美国国立卫生研究院的大型多中心研究，以预防儿童肥胖和2型糖尿病，发表在 新英格兰医学杂志。这项研究最终将使儿童健康专业人员，家庭， 社区领导人，以优化使用运动，以促进健康的关键时期的增长。

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.