[PDF][PDF] Alpha-ketoglutarate, an endogenous metabolite, extends lifespan and compresses morbidity in aging mice

AA Shahmirzadi, D Edgar, CY Liao, YM Hsu, M Lucanic… - Cell metabolism, 2020 - cell.com
AA Shahmirzadi, D Edgar, CY Liao, YM Hsu, M Lucanic, AA Shahmirzadi, CD Wiley, G Gan…
Cell metabolism, 2020cell.com
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 …
Summary
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.
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