Epigenetic Mechanisms Linking Lifetime Social and Environmental Exposures to Cognitive Aging

项目总结/摘要 拟议的项目将表观遗传流行病学和方法的培训与一项研究相结合， 该项目探讨了表观遗传学如何提供对终身社会和 环境暴露会影响老年人的认知老化。该培训和研究计划将 促进过渡到生命过程研究，社会基因组学领域的独立研究人员， 阿尔茨海默病和相关痴呆症（ADRD）为Mateo Farina博士。获得博士学位在 社会学（人口统计学重点）从得克萨斯大学奥斯汀分校，他研究的生命历程 美国黑人和白人痴呆症发病的起源。作为一名NIA支持的博士后 作为南加州大学戴维斯老年学学院的研究员，他已经开始 将生物标志物纳入他的工作，现在将扩大这些包括表观遗传标记。 表观遗传学，定义为基于DNA甲基化和RNA转录组的措施，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， 发展（即，海马体积较低），但它也可以影响脑病理学（即增加 淀粉样蛋白）。通过这些生物学途径，认知老化结果不佳的风险，如认知能力下降， 亏损，增加。这种与大脑健康的联系使得表观遗传学对这项研究具有潜在的重要性 的ADRD。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 这是一个可以检查的机制，以评估生命过程暴露如何影响认知老化。拟议 研究将通过以下方式推动衰老领域的发展：1）提高我们对表观遗传学如何影响衰老的理解。 与认知功能和变化的多项测量中的认知老化相关，2）调查 基于表观遗传的生物社会途径，将终生的社会和环境暴露与认知能力联系起来， 衰老和3）了解表观遗传学如何可能导致下游生理失调， 与认知健康不良有关。 这项拟议中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，沿着丰富的信息， 认知和社会和经济条件，使研究表观遗传成为可能。 在一个大的，不同的国家， 代表人口。南加州大学提供了理想的培训环境，进行这项研究，鉴于 老年学学院的多学科性质，认知老化方面的专业知识，以及几种教学选择 接受表观遗传学方法的培训该培训将使PI准备作为初级人员提交R 01提案 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.