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，既可以正面调节基因表达，也可以负面调节基因表达。虽然甲基化在驱动许多细胞特异性和组织特异性功能中起着关键作用，但现在公认的是，DNA的一些(但不是全部)表观遗传修饰也可能发生，以响应环境的变化。重要的是，这些变化可以稳定地改变基因表达，从而可能影响新陈代谢、行为，最终影响整体健康。运动已被证明对身体和心理健康结果都有积极的影响，但运动后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检查提供了证据，表明甲基化对运动训练相关的生理变化不稳定，这种易感性可能是基因组背景的函数。我们对3000多名接受有氧运动训练的人进行了广泛的研究，这些人使用了精心控制和有文件记录的有氧运动养生法。我们收集了多个与运动耐量相关的参数，包括心率、强度、持续时间和总运动暴露。此外，我们还收集了运动前和运动后约1500人的DNA和RNA。在这个项目中，我们计划对久坐不动的个体在运动前和运动后的训练中的全基因组甲基化和基因表达进行表征，以确定基因调控变化的主要靶点。这项研究有可能揭示影响对健康行为(如体力活动)做出反应或保持健康行为的能力的机制。

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.