Alpha-Ketoglutarate, an Endogenous Metabolite, Extends Lifespan and Compresses Morbidity in Aging Mice

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 an...

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Published in:Cell metabolism Vol. 32; no. 3; p. 447
Main Authors: Asadi Shahmirzadi, Azar, Edgar, Daniel, Liao, Chen-Yu, Hsu, Yueh-Mei, Lucanic, Mark, Asadi Shahmirzadi, Arash, Wiley, Christopher D, Gan, Garbo, Kim, Dong Eun, Kasler, Herbert G, Kuehnemann, Chisaka, Kaplowitz, Brian, Bhaumik, Dipa, Riley, Rebeccah R, Kennedy, Brian K, Lithgow, Gordon J
Format: Journal Article
Language:English
Published: United States 01.09.2020
Subjects:
frailty
inflammation
alpha-ketoglutarate
lifespan
longevity
healthspan
SASP
IL-10
ISSN:1932-7420, 1932-7420
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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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ISSN:1932-7420
1932-7420
DOI:10.1016/j.cmet.2020.08.004