Location: Jean Mayer Human Nutrition Research Center On Aging
Project Number: 8050-51000-098-000-D
Project Type: In-House Appropriated
Start Date: Oct 26, 2014
End Date: Sep 30, 2019
1: Identify metabolomic-based biomarkers of dietary and exercise behavior in normal-weight and obese elderly individuals and the genetic variants associating with the baseline levels of these metabolites. 1.A. Identify metabolomic-based biomarkers of dietary behavior in normal-weight and obese aging individuals and the genetic variants associating with endogenous variability of these metabolites. 1.B. Identify metabolomic-based biomarkers of physical activity in normal-weight and obese aging individuals and the genetic variants associating with endogenous variability of these metabolites. 2: Determine the demographic, behavioral, metabolomic and genetic drivers of the excess obesity in elderly population(s) suffering health disparity. 3: Determine the relationships between aging-related changes in gene expression, endogenous and exogenous microRNAs, metabolic factors and chronotype in response to metabolic challenges such as unhealthy dietary habits, high-fat loads and physical inactivity. 4: Identify genomic, and epigenomic and metabolic markers that predict cardiovascular status and metabolic health during aging and define specific dietary, physical activity and other lifestyle factors that are most suitable to an individual’s genetic and epigenetic profile. 5: Use a multi-omics approach to identify multi-level genome/metagenome/diet interactions that modulate inflammation and aging pathways in normal-weight and obese individuals. 5.A. Determine which of a panel of aging and obesity-related phenotypes associate with genetic markers of obesity in an obese-non-obese comparison (or, in a manner dependent on obesity status) and which of those genetic associations are modulated by dietary factors and exercise. 5.B. Assess microRNA expression levels as correlating with the obese condition irrespective of genetics. 5.C. Collect metabolomics data to define individuals metabolically as obese or non-obese, irrespective of anthropometrics. 5.D. Perform gene network, systems biology analysis on those genes and genetic markers showing associations, either modified by diet or exercise or not, with the aging and obesity-related phenotypes.
Our research on the genetic basis of the responses to diet and their metabolic consequences has demonstrated that the onset and progression of age-related disorders depends on an individual’s metabolic flexibility. With respect to cardiometabolic diseases several factors act in concert and converge to challenge metabolic flexibility. These include an inadequate diet, insufficient physical activity, chronodisruption, decreased metabolic reserve, altered gut microbiome, and reduced immune system capacity. Our primary focus is to determine the specific elements from each of these factors that interact together and with common genetic variants to either promote or disrupt a program of metabolic flexibility in the context of aging, obesity and cardiovascular disease. Our approach aims to identify new metabolite-based markers, substantiate intake of certain foods, nutrients or dietary patterns, define the degree and mechanisms by which circadian control affects cardiometabolic diseases, to describe the roles of microRNAs in these diseases, and to do so in the context of populations suffering health disparities. This will be tested, using high throughput “omic” (i.e., genomics, epigenomics, metabolomics) techniques, both in ongoing studies of free-living populations from different ethnic groups and in intervention studies. We also propose to establish statistical methods whereby a genome-optimized diet is evaluated for its ability to lower plasma triglycerides. Lastly, available datasets will be used to construct gene-SNP-metabolite-diet-aging networks for the purpose of generating testable hypotheses relevant to delaying the onset and progression of cardiometabolic disorders. Outcomes of this research will generate new and better strategies for the prevention of age-related disorders and for slowing the aging process using nutritional and behavioral approaches.