Alpha-Ketoglutarate, an Endogenous Metabolite, Extends Lifespan and Compresses Morbidity in Aging Mice.
Alpha-Ketoglutarate, an Endogenous Metabolite, Extends Lifespan and Compresses Morbidity in Aging Mice.
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DOI：
10.1016/j.cmet.2020.08.004
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发表时间：
2020-09-01
期刊：
影响因子：
29
通讯作者：
Lithgow GJ
中科院分区：
文献类型：
--
作者：
Asadi Shahmirzadi A;Edgar D;Liao CY;Hsu YM;Lucanic M;Asadi Shahmirzadi A;Wiley CD;Gan G;Kim DE;Kasler HG;Kuehnemann C;Kaplowitz B;Bhaumik D;Riley RR;Kennedy BK;Lithgow GJ
新陈代谢和衰老是紧密相连的。α-酮戊二酸是三羧酸（TCA）循环中的关键代谢产物，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C57 BL/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可以促进更长寿、更健康的生活，并降低全身炎症细胞因子的水平。我们提出，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，至少在鼠模型中，导致发病率的压缩。Asadi Shahmirzadi等人报告说，补充α-酮戊二酸的饮食延长了中年雌性小鼠的寿命，并增加了两性小鼠的健康寿命。随着虚弱程度的降低和寿命的延长，干预措施降低了发病率。AKG抑制慢性炎症并诱导雌性小鼠T细胞分泌IL-10。
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. Asadi Shahmirzadi et al. report that an alpha-ketoglutarate-supplemented diet extends lifespan of middle-aged female mice and increases healthspan in both sexes. With simultaneous reduction in frailty and increase in longevity, the intervention compresses morbidity. AKG suppresses chronic inflammation and induces secretion of IL-10 in T cells of female mice.
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DOI：
10.1093/gerona/glw149
发表时间：
2016-11
期刊：
The journals of gerontology. Series A, Biological sciences and medical sciences
影响因子：
--
作者：
Newman JC;Milman S;Hashmi SK;Austad SN;Kirkland JL;Halter JB;Barzilai N
通讯作者：
Barzilai N
影响因子：
3
作者：
Lento, Jennifer;Dillon, Peter J.;Somers, Keith M.
通讯作者：
Somers, Keith M.
DOI：
10.1073/pnas.92.20.9363
发表时间：
1995-09-26
影响因子：
11.1
作者：
DIMRI, GP;LEE, XH;CAMPISI, J
通讯作者：
CAMPISI, J
DOI：
10.1093/gerona/glu315
发表时间：
2016-03-01
影响因子：
5.1
作者：
Kane, Alice E.;Hilmer, Sarah N.;Mitchell, Sarah J.
通讯作者：
Mitchell, Sarah J.
影响因子：
--
作者：
BLAND, JM;ALTMAN, DG
通讯作者：
ALTMAN, DG