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

体力活动分子传感器儿科临床中心(MoTrPAC)：走向 运动在儿科生命健康起源中的分子图谱 这项研究的目标是：1)绘制运动有益于健康的分子机制图 儿童和青少年，人类表型变化的关键时期，2)提供MoTrPAC 来自儿童和青少年运动研究的严格收集和可重复的数据的联盟。 这一建议是基于一系列学科中令人兴奋的发现，包括：1)对年龄的新见解- 儿童生长过程中基因表达的依赖进展，2)新出现的数据强调中央 白细胞(N.B.，儿童健康研究中一种可获得的组织)在将运动转化为 健康益处，3)试点数据显示生长和生长的分子转导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、代谢和白细胞功能以及转录反应 运动诱导的细胞内稳态的短暂扰动将在早期和 青春期晚期的男孩和女孩。在拟议的慢性运动研究中(12周，预期的，有氧的 运动训练干预)，我们将比较生物标记物和分子适应的大小 青春期早期和晚期之间的训练以及伴随的形态和生理变化 女孩们男孩们。来自急性和慢性运动研究的综合数据将通过系统进行分析- 将体力活动与成长中的儿童的健康联系起来的网络的计算技术 和青春期。因为表型在生长过程中是一个“移动的目标”，我们将使用精确的方法。 (例如用于身体成分的DXA和用于心肺运动测试的呼吸气体交换) 在我们手中已被证明在大量儿童和青少年中是可行的。传统运动 测试将得到基于实验室的“真实”锻炼方案的补充，并且在所有情况下，都要根据每种情况进行调整 参与者的身体健康，对习惯性体力活动的估计，血管健康的非侵入性测量， 培训的数量和方式。通过这种方式，儿科和成人数据将很容易地整合在一起。作为一种 学术健康中心单位致力于儿童体力活动和健康的研究 在不同的地区，我们的集团非常有资格为MoTrPAC财团做出贡献。我们1)出版了 循环白细胞中新的基因组和表观遗传运动生物标志物的一系列发现 儿童和成人，2)进行了数千次儿科运动测试，3)成功地进行了许多 青春期早期和晚期儿童的前瞻性运动训练干预，4)是项目的领导者 Healthy，美国国立卫生研究院预防儿童肥胖和2型糖尿病的大型多中心研究，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、家庭和 社区领导人在关键的成长期优化利用运动来促进健康。

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.