α-酮戊二酸，一种内源性代谢物，可延长衰老小鼠的寿命并压缩发病。
Alpha-Ketoglutarate, an Endogenous Metabolite, Extends Lifespan and Compresses Morbidity in Aging Mice.
机构信息
The Buck Institute for Research on Aging, 8001 Redwood Blvd., Novato, CA 94945, USA; USC Leonard Davis School of Gerontology, University of Southern California, 3715 McClintock Ave., Los Angeles, CA 90191, USA.
The Buck Institute for Research on Aging, 8001 Redwood Blvd., Novato, CA 94945, USA.
出版信息
Cell Metab. 2020 Sep 1;32(3):447-456.e6. doi: 10.1016/j.cmet.2020.08.004.
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.
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，其水平在禁食、运动和衰老时会发生变化。在这里，我们研究了α-酮戊二酸（以钙盐的形式 CaAKG 提供）对 C57BL/6 小鼠健康寿命和寿命的影响。为了探究哺乳动物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 可促进更长、更健康的寿命，同时降低系统性炎症细胞因子的水平。我们提出，饮食中 AKG 诱导 IL-10 的产生可以抑制慢性炎症，从而带来健康益处。通过同时减少虚弱和增强长寿，AKG 至少在小鼠模型中导致发病减少。
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