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

Overview

Journal Cell Metab

Publisher Cell Press

Specialties Cell Biology
Endocrinology

Date 2020 Sep 3

PMID 32877690

Citations 151

Authors

Azar Asadi Shahmirzadi

Daniel Edgar

Chen-Yu Liao

Yueh-Mei Hsu

Mark Lucanic

Arash Asadi Shahmirzadi

Christopher D Wiley

Garbo Gan

Dong Eun Kim

Herbert G Kasler

Chisaka Kuehnemann

Brian Kaplowitz

Dipa Bhaumik

Rebeccah R Riley

Brian K Kennedy

Gordon J Lithgow

Affiliations

Soon will be listed here.

Abstract

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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