Epigenetic and Genetic Mechanisms Driving Exercise Response and Adherence

描述（由申请人提供）：甲基化是一种表观遗传机制，可以正向和负向调节基因表达。尽管甲基化在驱动许多细胞特异性和组织特异性功能中起关键作用，但现在已经确定，DNA的一些而不是全部表观遗传修饰也可能响应于环境的变化而发生。重要的是，这些变化可以稳定地改变基因表达的方式，可能会影响新陈代谢，行为，并最终整体健康。运动已被证明对身体和精神健康都有积极的影响，但运动后推动健康稳定变化的确切分子机制尚不清楚。我们对运动训练前后甲基化状态的初步研究提供了证据，表明甲基化对与运动训练相关的生理变化不稳定，并且这种倾向可能是基因组背景的函数。我们进行了广泛的研究，描述了3,000多名使用精心控制和记录的有氧运动方案进行有氧运动训练的人。我们收集了与运动耐量相关的多个参数，包括心率、强度、持续时间和总运动暴露量。此外，我们还从大约1,500名运动前和运动后的个体中提取了DNA和RNA。在这个项目中，我们计划描述久坐个体运动训练前后的全基因组甲基化和基因表达，以确定基因调控改变的主要靶点。这项研究有可能揭示影响对身体活动等健康行为做出反应或保持健康行为的能力的机制的新见解。

DESCRIPTION (provided by applicant): Methylation is an epigenetic mechanism that can both positively and negatively regulate gene expression. Although methylation serves a critical role in driving many cell-specific and tissue- specific functions, it is now well-established that some, bu not all, epigenetic modifications of DNA may also occur in response to changes in the environment. Importantly, these changes can stably alter gene expression in a manner that may influence metabolism, behavior, and ultimately overall health. Exercise has been shown to have positive effects on both physical and mental health outcomes but the exact molecular mechanism driving stable changes in health following exercise are not well known. Our initial examination of methylation states before and after exercise training has provided evidence that methylation is labile to physiologic changes associated with exercise training, and that this liability may be a function of genomic background. We have performed extensive research characterizing over 3,000 individuals undergoing aerobic exercise training using a carefully-controlled and documented aerobic exercise regimen. We have collected multiple parameters related to exercise tolerance, including heart rate, intensity, duration, and total exercise exposure. In addition, we have both DNA and RNA from approximately 1,500 individuals, both pre- and post-exercise. In this project, we plan to characterize both whole genome methylation and gene expression in sedentary individuals' pre- and post-exercise training in order to identify the primary targets of alterations in gene regulation. This research has the potential to reveal new insights into the mechanisms that influence the ability to respond to or maintain health behaviors like physical activity.