Grant: Discovery Grants Program - Individual

This proposal deals exclusively with fundamental aspects of fatty acid and ketone body (ketone) metabolism during HEALTHY human aging. As the engine behind physiological processes, energy metabolism has a major impact on two important aspects of quality of life - brain function and physical fatigue - both of which assume greater importance during aging. The brain accounts for nearly ¼ of the energy requirements of the adult human body at rest and is a major consumer of ketones whenever glucose is less available for prolonged periods. Ketone production is dependent on fatty acid oxidation. Therefore, if there are 'obligatory' (physiological) changes in energy metabolism as humans age, we expect that fatty acid metabolism and ketone synthesis would be affected. Our goal is to develop a clearer understanding the physiology of fatty acid and ketone metabolism in the healthy elderly so as to provide a better foundation for developing more effective strategies aimed at maintaining optimal health and quality of life throughout adulthood. We carefully screen for HEALTHY elderly subjects. We use metabolic tests with stable isotope-labeled fatty acids and beta-hydroxybutyrate, and dietary supplements or specific pharmaceuticals to safely probe fatty acid oxidation and ketone production. Though not exhaustive, our metabolic test protocols are sufficiently detailed and well established in our lab to give us confidence that we can identify changes in fatty acid or ketone metabolism that are truly related specifically to the physiology of aging, i.e. they occur in healthy individuals and are not due to accompanying disease. Power analysis based on our preliminary studies suggests that 10-12 subjects/age group are sufficient for these studies. These studies may eventually lead to recommendations for how to protect optimal energy metabolism in younger and middle-aged adults, thereby possibly protecting brain function in the elderly.