Project Number: 8050-51000-084-02-S
Project Type: Non-Assistance Cooperative Agreement
Start Date: Jun 11, 2015
End Date: Sep 30, 2019
Objective 1: Characterize the effects of genetic, metabolic, and environmental influences on the aging brain and vasculature and the modifying impact of nutrition on neuronal function, cognition, and behavioral outcomes. Sub-objective 1A: Use human observational data to evaluate the relationships between nutrients/ bioactives, age-related cognitive decline, and neurodegenerative diseases, and characterize interactions between diet and genes, and environmental influences on these outcomes. Sub-objective 1B: Use human intervention studies as translational studies to determine the effects of intervention with specific nutrients or bioactives on cognitive and behavioral function. Sub-objective 1C: Use animal and cell models to develop mechanistic interpretations of the benefits of nutrients and bioactives to the brain in aging models in rodents. Determine the mechanisms related to the behavioral effects of nutrients and bioactives on biomarkers of inflammation and oxidative response. Objective 2: Characterize molecular, cellular, and physiological mechanisms by which food and nutritional factors affect the Central Nervous System regulation of aging processes and energy homeostasis. Sub-objective 2A: Assess whether age-related inflammation affects the cell genesis and cellular structure of the hypothalamus. Sub-objective 2B: Evaluate whether dietary intervention and natural products can be used to counteract age-related biochemical and structural changes in the hypothalamus. Sub-objective 2C: Assess whether dietary/natural product intervention attenuates systemic aging.
This project will utilize in vitro and in vivo studies on the mechanisms of action of nutrients and bioactives in improving brain function during aging. In particular, with a focus on age-related cognitive decline, including that associated with Alzheimer’s Disease, two objectives will focus on 1. The effects of genetic, metabolic, and environmental influences on the aging brain and vasculature and the modifying impact of nutrition on neuronal function, cognition, and behavioral outcomes. In addition to human observational data, cell and animal models will help resolve mechanisms underlying the benefits of nutrients and bioactives in the aging brain using rodent models. These studies will rely on inflammatory and oxidative stress molecular biomarkers as read outs of the preventative and potential disease attenuating attributes of diet and nutrition; and, 2. The characterization of molecular, cellular and physiological mechanisms by which food and particular combinations of phytocompounds act as nutritional and disease preventing/ treating factors for the aging central nervous system. In particular, the testing of a new theory of interactive brain and body aging will define age-related inflammation effects on cell genesis and cellular structure of the hypothalamus. In all, the studies proposed here, utilizing state of the art genetic, molecular, cellular and behavioral methodologies, will elucidate whether and how dietary/natural product intervention attenuates negative aspects of systemic aging.