Location: Jean Mayer Human Nutrition Research Center On Aging
Project Number: 8050-51000-107-001-S
Project Type: Non-Assistance Cooperative Agreement
Start Date: Oct 1, 2019
End Date: Sep 30, 2023
Objective 1: Conduct and analyze dietary intervention studies to validate gene-diet interactions and identify the underlying mechanisms using omic technologies. Sub-Objective 1A: To characterize the response of cardiometabolic, epigenetics and other age-related biomarkers and the microbiome to diets differing in saturated fat and prebiotics content (animal-based diet versus plant-based diet) in individuals carrying CC and TT genotypes at the common APOA2 -265T>C (rs5082) SNP using a shortterm crossover, randomized feeding study, and to elucidate the physiological mechanism(s) by which diet impinges on metabolic pathways through APOA2 genotypes. Sub-Objective 1B: To characterize the TCF7L2-by-diet interaction with respect to those type 2 diabetes (T2D) and cardiovascular disease (CVD) risk factors identified in observational studies for validation in the context of a short-term randomized controlled feeding study (low-fat diet versus Mediterranean diet), and to elucidate the molecular mechanisms responsible for these GxD interactions using epigenetics and metabolomics. Sub-Objective 1C: To develop polygenic risk scores (PRS) predicting the changes in and relationships between cardiovascular disease (CVD) risk factors and disease incidence in response to long-term (>=1 y) dietary interventions [Mediterranean diet (MedDiet) or Low-fat control diet]. Objective 2: Identify genomic, epigenomic, metabolomic, and microbiome-related biomarkers that sustain healthy aging, and define specific personalized dietary, physical activity, and other lifestyle factors associated with optimal health of older adults. Subobjective 2A: To identify genetic and dietary factors that modify CPT1A methylation and cardio-metabolic traits. Subobjective 2B: To identify interactions between the genome, epigenome and diet and lifestyle on lipid profiles that signify CMD risk.
Promoting healthy aging by tailoring nutritional guidance based on a person's genetic makeup is an emerging science that has great promise. The Nutrition and Genomics lab is a pioneer in this area and focuses its research on the role of precision nutrition and cardiometabolic diseases – the leading cause of death in the United States. Our approach harnesses the availability of tremendous computing power and huge datasets from existing cohorts to study the crosstalk between habitual diets and the genome to identify gene-by-diet interactions that sustain individual optimal health for older adults. This objective will be accomplished using Big Data analytics of omics data (i.e., genome-wide datasets on gene and protein expression, genetic variation, methylation, and metabolite levels). We also conduct short-term feeding studies in people preselected based on particular genotypes to validate gene-by-diet interactions revealed by previous observational studies and, using multi-omic data integration (i.e., genomics, epigenomics, microbiomics, and metabolomics) methods, identifying the mechanisms underlying such interactions. This research will generate new knowledge on how non-modifiable and modifiable factors interact to prevent cardiovascular diseases and type 2 diabetes. Further, it will contribute much-needed evidence and tools to define and implement personalized nutrition as a common practice for the benefit of all stakeholders.