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.

Project Narrative Both cognitive aging and epigenetic change appear to be highly influenced by life experiences, and this project will examine how these are linked. The project has two main objectives: (1) to examine how DNA methylation and RNA transcriptomes are tied to several measures of cognitive status and change, and (2) to examine how life experiences are biologically embedded via epigenetic mechanisms to impact cognitive aging. Findings from this study will add significantly to research on the life course origins of dementia and cognitive aging by taking into account how lifetime social and environmental exposures and their timing impact cognition in older life via DNA methylation and gene expression, and it may point to potential areas of intervention to improve the cognitive health of the population.