Interacting mechanisms of sleep and aerobic fitness: Implications for health in the growing child

摘要 导致心血管疾病的危险因素起源于儿童和青少年， 成年期，并对长期的生物心理社会健康产生有害影响。表型睡眠和健身是 与心血管疾病的发生和进展机制密切相关 及其风险因素（例如，体重指数升高、肥胖、代谢综合征、血脂升高， 血压升高、炎症、自主神经系统失衡、营养不良和饮食不良，以及 身体活动不足）。睡眠和健身是与健康相关的重要的相互作用的生理功能。 强大的代谢，激素和认知反应，以及基因组和代谢组学适应性 机制等睡眠不足和健康状况不佳在年轻人中普遍存在， 在整个生命周期中，急性健康威胁和疾病风险增加。然而，人们对此知之甚少。 潜在的机制途径，管理健康和睡眠之间的相互作用，在发展青年， 它们对心血管疾病风险的调节作用。这项拟议的研究旨在填补一个关键的空白， 了解睡眠和健身如何相互作用，影响心血管疾病的风险因素。在这里我们建议 一项针对多中心NIH的身体活动分子传感器联盟（MoTrPAC）的辅助研究 共同基金项目，旨在发现分子转换器（“分子图谱”）负责 身体活动和健身对人类整个生命周期的有益健康影响。添加睡眠 对儿科MoTrPAC研究的评估为开始阐明 在青春期过渡期间，健康和睡眠的相互作用机制， 生理、神经生物学和心理发展。该项目建议评估一组 完成MoTrPAC协议的成熟阶段的儿童和青少年，其中包括两个 阶段：横断面阶段和耐力运动干预阶段。值得注意的是，这项辅助研究 不改变现有的MoTrPAC方案/干预，不包括任何额外的干预， 因此不被认为是临床试验。本研究将从儿科MoTrPAC研究中招募受试者 并在每个MoTrPAC阶段结束时评估睡眠的表型测量。获得的数据将允许 探索青春期健康-睡眠相互作用的基本机制途径， 指导未来临床试验的发展，旨在确定最佳的睡眠锻炼方案， 包括不同种族/民族群体和医学上的不同的青少年群体的心理健康状况， 高危人群。此外，这项研究的结果将被添加到MoTrPAC数据库中， 和独特的数据集，用于进一步探索睡眠之间的基因组，代谢组学和蛋白质组学相互作用。 和健康，因为它们影响心血管疾病因素。

ABSTRACT The risk factors that contribute to cardiovascular disease originate in childhood and adolescence, track into adulthood, and have deleterious effects on long-term biopsychosocial health. Phenotypic sleep and fitness are strongly associated with mechanisms involved in the development and progression of cardiovascular disease and its risk factors (e.g., elevated body-mass index, adiposity, metabolic syndrome, elevated serum lipids, elevated blood pressure, inflammation, autonomic nervous system imbalance, poor nutrition and diet, and physical inactivity). Sleep and fitness are essential interacting physiological functions that are associated with robust metabolic, hormonal, and cognitive responses, as well as with genomic and metabolomic adaptive mechanisms. Both insufficient sleep and poor fitness are at epidemic proportions in youth and are associated with acute health threats and increased disease risk across the lifespan. However, little is known about the underlying mechanistic pathways that govern the interactions between fitness and sleep in developing youth in their modulation of cardiovascular disease risk. This proposed study aims to fill a crucial gap in the understanding how sleep and fitness interact to impact cardiovascular disease risk factors. Here we propose an ancillary study to the Molecular Transducers of Physical Activity Consortium (MoTrPAC), a multicenter NIH Common Fund project that aims to discover the molecular transducers ("molecular map") responsible for the beneficial health effects of physical activity and fitness in humans across the lifespan. Adding sleep assessment to the pediatric MoTrPAC study offers a transformative opportunity to begin to elucidate the interacting mechanisms of the fitness and sleep in humans during adolescent transition, a critical period of physical, neurobiological, and psychological development. This project proposes to evaluate a cohort of children and adolescents across maturational stages who complete the MoTrPAC protocol, which includes two phases: a Cross-Sectional phase, and an Endurance Exercise Intervention phase. Of note, this ancillary study does not change the existing MoTrPAC protocol/intervention and does not include any additional interventions, and is therefore not considered a clinical trial. This study will recruit subjects from the pediatric MoTrPAC study and evaluate phenotypic measures of sleep at the end of each MoTrPAC phase. Data obtained will allow exploration of fundamental mechanistic pathways underlying fitness-sleep interactions during adolescence and guide development of future clinical trials aimed at determining optimal sleep-exercise regimens for physical and mental health in various adolescent populations, including different racial/ethnic populations and medically at-risk groups. In addition, results from this study will be added to the MoTrPAC data repository, yielding a rich and unique dataset for further exploration of genomic, metabolomic, and proteomic interactions between sleep and fitness as they impact cardiovascular disease factors.