Ketogenic Diet Reduces Midlife Mortality and Improves Memory in Aging Mice.
Ketogenic Diet Reduces Midlife Mortality and Improves Memory in Aging Mice.
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DOI：
10.1016/j.cmet.2017.08.004
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发表时间：
2017-09-05
期刊：
影响因子：
29
通讯作者：
Verdin E
中科院分区：
文献类型：
--
作者：
Newman JC;Covarrubias AJ;Zhao M;Yu X;Gut P;Ng CP;Huang Y;Haldar S;Verdin E
生酮饮食（KD）概括了饮食限制的某些代谢方面，如对脂肪酸代谢和酮体产生的依赖。我们研究了KD是否可能像饮食限制一样影响C57 BL/6雄性小鼠的寿命和健康。我们发现，一种同种蛋白KD，隔周喂养以防止肥胖（循环KD），降低了中年死亡率，但不影响最长寿命。类似喂养的非生酮高脂饮食（HF）可能对死亡率有中等影响。循环KD改善老年人的记忆表现，同时适度改善综合健康状况。基因表达分析确定胰岛素、TOR和脂肪酸合成途径的下调是KD和HF的共同机制。然而，PPARα靶基因的上调是KD独有的，在各组织中一致，并在老年时保留。总之，我们证明了非致肥生酮饮食可以改善衰老小鼠的存活率、记忆力和健康状况。生酮饮食在许多生理方面与饮食限制相似。纽曼等人表明，随着小鼠年龄的增长，循环生酮饮食降低了死亡率并改善了记忆。生酮饮食基因表达模式与高脂饮食相似，除了激活PPARα靶点。参见Roberts et al.的相关论文。
A ketogenic diet (KD) recapitulates certain metabolic aspects of dietary restriction such as reliance on fatty acid metabolism and production of ketone bodies. We investigated whether KD might, like dietary restriction, affect longevity and healthspan in C57BL/6 male mice. We find that an isoprotein KD, fed on alternate weeks to prevent obesity (Cyclic KD), reduces mid-life mortality but does not affect maximum lifespan. A non-ketogenic high-fat diet (HF) fed similarly may have an intermediate effect on mortality. Cyclic KD improves memory performance in old age, while modestly improving composite healthspan measures. Gene expression analysis identifies down-regulation of insulin, TOR, and fatty acid synthesis pathways as mechanisms common to KD and HF. However, up-regulation of PPARα target genes is unique to KD, consistent across tissues, and preserved in old age. In all, we show that a non-obesogenic ketogenic diet improves survival, memory, and healthspan in aging mice. Ketogenic diet is similar in many physiological respects to dietary restriction. Newman et al. show that a cyclic ketogenic diet reduces mortality and improves memory as mice age. Ketogenic diet gene expression pattern is similar to high-fat diet, except activation of PPARα targets. See related paper by Roberts et al.
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影响因子：
14.8
作者：
通讯作者：
--
影响因子：
29
作者：
Brandhorst S;Choi IY;Wei M;Cheng CW;Sedrakyan S;Navarrete G;Dubeau L;Yap LP;Park R;Vinciguerra M;Di Biase S;Mirzaei H;Mirisola MG;Childress P;Ji L;Groshen S;Penna F;Odetti P;Perin L;Conti PS;Ikeno Y;Kennedy BK;Cohen P;Morgan TE;Dorff TB;Longo VD
通讯作者：
Longo VD
影响因子：
7.7
作者：
Peleg S;Feller C;Forne I;Schiller E;Sévin DC;Schauer T;Regnard C;Straub T;Prestel M;Klima C;Schmitt Nogueira M;Becker L;Klopstock T;Sauer U;Becker PB;Imhof A;Ladurner AG
通讯作者：
Ladurner AG
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.
DOI：
10.1096/fj.201600773r
发表时间：
2016-12
期刊：
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
影响因子：
--
作者：
Murray AJ;Knight NS;Cole MA;Cochlin LE;Carter E;Tchabanenko K;Pichulik T;Gulston MK;Atherton HJ;Schroeder MA;Deacon RM;Kashiwaya Y;King MT;Pawlosky R;Rawlins JN;Tyler DJ;Griffin JL;Robertson J;Veech RL;Clarke K
通讯作者：
Clarke K