Metabolism and aging are tightly connected. Alpha-ketoglutarate is a key metabolite in the tricarboxylic acid (TCA) cycle, and its levels change upon fasting, exercise, and aging. Here, we investigate the effect of alpha-ketoglutarate (delivered in the form of a calcium salt, CaAKG) on healthspan and lifespan in C57BL/6 mice. To probe the relationship between healthspan and lifespan extension in mammals, we performed a series of longitudinal, clinically relevant measurements. We find that CaAKG promotes a longer, healthier life associated with a decrease in levels of systemic inflammatory cytokines. We propose that induction of IL-10 by dietary AKG suppresses chronic inflammation, leading to health benefits. By simultaneously reducing frailty and enhancing longevity, AKG, at least in the murine model, results in a compression of morbidity.
Competing Interests: Declaration of Interests G.J.L. and M.L. are co-founders of Gerostate Alpha, a company aimed at developing drugs for aging, and are shareholders in Ponce de Leon Health. D.E. and Azar Asadi Shahmirzadi are shareholders in Ponece de Leon Health. B.K.K. is a board member and equity holder at Ponce de Leon Health. G.J.L., B.K., M.L., D.E., and Azar Asadi Shahmirzadi are named inventors on a preliminary patent application related to this discovery.
(Copyright © 2020. Published by Elsevier Inc.)