Epigenetic Mechanisms Linking Lifetime Social and Environmental Exposures to Cognitive Aging

项目摘要/摘要 拟议的项目将表观流行病学和方法方面的培训与研究相结合。 该项目研究表观遗传学如何提供对终身社会和社会的生物嵌入的洞察 环境暴露会影响老年人的认知老化。这项培训和研究计划将 促进向生命历程研究、社会基因组学和 Mateo Farina博士的阿尔茨海默病和相关痴呆症(ADRD)。他于#年获得博士学位。 社会学(强调人口学)，毕业于德克萨斯大学奥斯汀分校，在那里他研究了人生历程 美国黑人和白人患痴呆症的原因。作为NIA支持的博士后 南加州大学戴维斯老年学学院的研究员，他已经开始 将生物标记物纳入他的工作，现在将扩大到包括表观遗传标记物。 表观遗传学被定义为基于DNA甲基化和RNA转录组的措施，它可以 对认知老化有重大影响。表观遗传学不仅可以影响大脑结构 发育(即较低的海马体体积)，但也会影响脑病理(即增加 淀粉样蛋白)。通过这些生物途径，认知老化结果不良的风险，如认知 损伤，增加。这种与大脑健康的联系使表观遗传学对这项研究具有潜在的重要性 是ADRD的。表观遗传学也很大程度上受到生活经历的影响。因此，这是一个重要的生物社会 可以研究的机制，以评估生命过程暴露如何影响认知老化。建议数 研究将通过以下方式推动老龄化领域的发展：1)提高我们对表观遗传学是如何 与认知老化有关的认知功能和变化的多个衡量标准，2)调查 基于表观遗传学的生物社会途径，将终生的社会和环境暴露与认知联系起来 衰老和3)了解表观遗传学如何导致下游生理失调 与认知健康状况不佳有关。 这项拟议的研究使用了新发布的DNA甲基化数据和即将发布的 《健康与退休研究》中的RNA转录组数据。这些数据，以及关于 认知以及一生中的社会和经济条件，使检查表观遗传学成为可能 在一个大而多样的全国范围内，将生命过程暴露及其时机与认知老化联系起来的机制 有代表性的人口。南加州大学提供了进行这项研究的理想培训环境，因为 老年学学派的多学科性质、认知老化方面的专业知识和几种说教选择 用于表观遗传学方法的培训。此培训将使PI准备好作为初级人员提交R01建议书 终身教授。

Project Summary/Abstract The proposed project integrates training in epigenetic epidemiology and methods with a research project that examines how epigenetics may provide insight into the biological embedding of lifetime social and environmental exposures that influence cognitive aging at older ages. This training and research plan will facilitate the transition to an independent researcher in the field of life course research, social genomics, and Alzheimer's Diseases and Related Dementias (ADRD) for Dr. Mateo Farina. He received his Ph.D. in Sociology (Demography Emphasis) from the University of Texas at Austin where he researched the life course origins of dementia onset among Blacks and Whites in the United States. As an NIA-supported postdoctoral fellow at the Davis School of Gerontology at the University of Southern California (USC), he has begun to incorporate biomarkers into his work and will now expand these to include epigenetic markers. Epigenetics, which is defined as measures based on DNA methylation and the RNA transcriptome, can have a significant impact on cognitive aging. Not only can epigenetics effect brain structure during development (i.e., lower hippocampal volume), but also it can influence brain pathology (i.e. increased amyloid). Through these biological pathways, the risk of poor cognitive aging outcomes, such as cognitive impairment, increases. This connection to brain health has made epigenetics potentially important for the study of ADRD. Epigenetics is also greatly influenced by life experiences. As such, it is an important biosocial mechanism that can be examined to evaluate how life course exposures impact cognitive aging. The proposed research will push the aging field forward by: 1) advancing our understanding of how epigenetics are associated with cognitive aging across multiple measures of cognitive functioning and change, 2) investigate the epigenetic-based biosocial pathways that link lifetime social and environmental exposures to cognitive aging and 3) understanding how epigenetics may lead to downstream physiological dysregulation that has been linked to poor cognitive health. The proposed research uses the newly released DNA methylation data and the soon-to-be released RNA transcriptome data in the Health and Retirement Study. This data, along with the rich information on cognition and social and economic conditions throughout life, make it possible to examine the epigenetic mechanisms linking life course exposures and their timing to cognitive aging in a large, diverse nationally representative population. USC provides the ideal training environment to undertake this research given the multidisciplinary nature of the School of Gerontology, expertise in cognitive aging, and several didactic options for training in epigenetic methods. This training will prepare the PI to submit an R01 proposal as a junior tenure-track professor.