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.

新陈代谢和衰老密切相关。α-酮戊二酸是三羧酸 (TCA) 循环中的关键代谢物，其水平会随着禁食、运动和衰老而变化。在这里，我们研究了 α-酮戊二酸（以钙盐 CaAKG 的形式提供）对 C57BL/6 小鼠健康和寿命的影响。为了探讨哺乳动物的健康寿命和寿命延长之间的关系，我们进行了一系列纵向的、临床相关的测量。我们发现 CaAKG 促进了与全身炎症细胞因子水平降低相关的更长、更健康的生活。我们建议通过饮食 AKG 诱导 IL-10 抑制慢性炎症，从而带来健康益处。通过同时减少虚弱和延长寿命，AKG，至少在小鼠模型中，导致发病率的压缩。