Epigenetic Mechanisms Linking Lifetime Social and Environmental Exposures to Cognitive Aging

将终生社会和环境暴露与认知衰老联系起来的表观遗传机制

• 批准号: 10429698
• 负责人: Matthew Farina
• 金额: $ 10万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-15 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10429698
• 关键词: Address; Adult; Age; Aging; Alzheimer' s Disease Pathway; Alzheimer' s disease related dementia; Amyloid; Area; Award; Biological; Biological Markers; Biological Process; Biometry; Biosocial; Black Populations; Brain; Brain Pathology; California; Childhood; Cognition; Cognitive; Cognitive aging; Collection; Complement; DNA Methylation; Data; Dementia; Demography; Deterioration; Development; Disease; Doctor of Philosophy; Down-Regulation; Economic Conditions; Elderly; Environment; Environmental Exposure; Epidemiology; Epigenetic Process; Etiology; Exposure to; Flow Cytometry; Gender; Gene Expression; Genes; Genome; Gerontology; Health; Health and Retirement Study; Hippocampus (Brain); Impaired cognition; Inflammation; Intervention; Lead; Life; Life Cycle Stages; Life Experience; Link; Measures; Methodology; Methods; Modification; National Institute on Aging; Nature; Outcome; Pathway interactions; Physiological; Policies; Population; Population Study; Postdoctoral Fellow; Public Health; RNA; Race; Research; Research Personnel; Research Project Grants; Research Training; Risk; Sampling; Schools; Shapes; Site; Social Conditions; Social Environment; Sociology; Structure; Synapses; Techniques; Testing; Texas; Training; United States; Universities; Up-Regulation; Venous blood sampling; Work; austin; base; brain health; cardiovascular risk factor; cognitive change; cognitive function; dementia risk; epigenetic marker; experience; falls; immune function; improved; insight; multidisciplinary; population health; professor; sex; skills; social; social genomics; tenure track; transcriptome; transcriptome sequencing

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.

项目摘要/摘要 拟议的项目将表观遗传流行病学和方法的培训与研究结合起来 研究表观遗传学如何提供对终身社会和 环境暴露会影响老年年龄的认知衰老。该培训和研究计划将 促进向生活课程研究，社会基因组学和 阿尔茨海默氏症的疾病和相关痴呆症（ADRD）为Mateo Farina博士。他获得了博士学位在 德克萨斯大学奥斯汀分校的社会学（人口统计学）在那里他研究了生活课程 美国黑人和白人之间痴呆症发作的起源。作为NIA支持的博士后 南加州大学（USC）的戴维斯老年学院研究员 将生物标志物纳入他的工作中，现在将它们扩展到包括表观遗传标记。 表观遗传学定义为基于DNA甲基化和RNA转录组的度量，可以 对认知衰老有重大影响。表观遗传学不仅可以影响大脑结构 发育（即海马体积较低），但也会影响脑病理学（即增加 淀粉样蛋白）。通过这些生物学途径，认知衰老结果不良的风险，例如认知 损害，增加。与大脑健康的这种联系使表观遗传学对研究至关重要 Adrd。表观遗传学也受到生活经历的极大影响。因此，这是一个重要的生物社会 可以检查以评估生命过程如何影响认知衰老的机制。提议 研究将通过以下方式推动衰老领域的前进 与认知功能和变化的多种衡量指标的认知衰老相关，2）调查 基于表观遗传学的生物社会途径，将寿命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患有下游生理失调 与认知健康不良有关。 拟议的研究使用了新发布的DNA甲基化数据，即将发布的 健康和退休研究中的RNA转录组数据。这些数据，以及丰富的信息 一生的认知以及社会和经济状况，可以检查表观遗传学 将生活课程暴露及其时间与认知衰老联系起来的机制 代表人口。 USC提供了理想的培训环境来进行这项研究 老年学院的多学科性质，认知衰老方面的专业知识和几种教学选择 用于表观遗传学方法的培训。这项培训将使PI准备提交R01提案的初中 终身教授。