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)：迈向 运动在儿科终生健康起源中的分子图谱 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，2) 提供 MoTrPAC 联盟从儿童和青少年的运动研究中严格收集和可重复的数据。 该提案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）新出现的数据强调了核心 白细胞（注意，儿童健康研究中的一种可接近的组织）在将运动转化为 健康益处，3) 试验数据显示生长和生长的分子传感器之间存在显着的相互作用 运动的分子传感器，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反应。在拟议的急性运动研究中， 直接的生理学、蛋白质组学、代谢组学和白细胞功能以及转录组学反应 运动引起的细胞稳态扰动将在早期和早期的横截面中进行测量 青春期后期的男孩和女孩。在拟议的慢性运动研究中（为期 12 周的前瞻性有氧运动） 运动训练干预），我们将比较生物标志物和分子适应的程度 训练，以及青春期早期和晚期之间伴随的形态测量和生理变化 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： 计算技术绘制将身体活动转化为成长中儿童健康的网络 和青少年。由于表型是生长过程中的“移动目标”，因此我们将使用准确的方法 （例如用于身体成分的 DXA 和用于心肺运动测试的每次呼吸气体交换） 事实证明，这对大量儿童和青少年来说是可行的。传统运动 测试将得到基于实验室的“现实生活”锻炼方案的补充，并且在所有情况下，都会针对每个 参与者的身体素质、习惯性身体活动的估计、血管健康的无创测量、 以及训练量和模式。通过这种方式，儿科和成人数据将很容易整合。作为一个 学术健康中心单位专门致力于儿童身体活动和健康的研究 我们的团队分布在不同的地区，非常有资格为 MoTrPAC 联盟做出贡献。我们1）发布了 在循环白细胞中发现了一系列新的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测试，3) 进行了许多成功的测试 对青春期早期和晚期儿童进行前瞻性运动训练干预，4) 是该项目的领导者 HEALTHY，一项大型 NIH 多中心研究，旨在预防儿童肥胖和 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、家庭和 社区领导者在成长的关键时期优化锻炼的利用以促进健康。

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.