Leveraging Kynurenine Pathway Manipulation to Improve Metabolic Dysfunction and Extend Healthspan in Mice
The kynurenine pathway is a conserved, lifespan regulating molecular pathway that is activated by inflammation, and higher levels of kynurenine and its metabolites, are associated with obesity, chronic inflammation, metabolic syndrome, aging and frailty in mammals. Using mice as a model, Dr. Westbrook’s research aims to determine if suppression of the kynurenine pathway can beneficially alter energy metabolism and increase healthspan. To do this, he will track radiolabeled glucose metabolism in mice with genetically and pharmacologically suppressed kynurenine levels, to determine how energy metabolism is affected, and additionally, measure the effects of reduced kynurenines on physiological function, glucose metabolism, frailty and aging. These studies will improve understanding of the role kynurenines play in the development of dysregulated energy metabolism, increased inflammation and aging-related functional decline and frailty in mice. Long-term, this study will guide the development of kynurenine suppression therapies that promote healthy aging and extend healthspan in humans.
