A Ketogenic Diet Extends Longevity and Healthspan in Adult Mice

被引:329
作者
Roberts, Megan N. [1 ]
Wallace, Marita A. [2 ]
Tomilov, Alexey A. [1 ]
Zhou, Zeyu [1 ]
Marcotte, George R. [2 ]
Tran, Dianna [1 ]
Perez, Gabriella [1 ]
Gutierrez-Casado, Elena [7 ]
Koike, Shinichiro [3 ]
Knotts, Trina A. [1 ]
Imai, Denise M. [4 ]
Griffey, Stephen M. [4 ]
Kim, Kyoungmi [5 ]
Hagopian, Kevork [1 ]
Haj, Fawaz G. [3 ]
Baar, Keith [2 ,6 ]
Cortopassi, Gino A. [1 ]
Ramsey, Jon J. [1 ]
Alberto Lopez-Dominguez, Jose [1 ,8 ]
机构
[1] Univ Calif Davis, Sch Vet Med, Dept Mol Biosci, Davis, CA 95616 USA
[2] Univ Calif Davis, Dept Neurobiol Physiol & Behav, Sch Vet Med, Davis, CA 95616 USA
[3] Univ Calif Davis, Dept Nutr, Sch Vet Med, Davis, CA 95616 USA
[4] Univ Calif Davis, Comparat Pathol Lab, Sch Vet Med, Davis, CA 95616 USA
[5] Univ Calif Davis, Sch Med, Dept Publ Hlth Sci, Davis, CA 95616 USA
[6] Univ Calif Davis, Sch Med, Dept Physiol & Membrane Biol, Davis, CA 95616 USA
[7] Univ Cordoba, Dept Biol Celular Fisiol & Inmunol, Cordoba, Spain
[8] Buck Inst Res Aging, Novato, CA 94945 USA
关键词
CALORIE RESTRICTION; LIFE-SPAN; PROTEIN-INTAKE; C57BL/6J MICE; METHIONINE; RAT; REGENERATION; METABOLITES; RESISTANCE; STRESS;
D O I
10.1016/j.cmet.2017.08.005
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Calorie restriction, without malnutrition, has been shown to increase lifespan and is associated with a shift away from glycolysis toward beta-oxidation. The objective of this study was to mimic this metabolic shift using low-carbohydrate diets and to determine the influence of these diets on longevity and healthspan in mice. C57BL/6 mice were assigned to a ketogenic, low-carbohydrate, or control diet at 12 months of age and were either allowed to live their natural lifespan or tested for physiological function after 1 or 14 months of dietary intervention. The ketogenic diet (KD) significantly increased median lifespan and survival compared to controls. In aged mice, only those consuming a KD displayed preservation of physiological function. The KD increased protein acetylation levels and regulated mTORC1 signaling in a tissue-dependent manner. This study demonstrates that a KD extends longevity and healthspan in mice.
引用
收藏
页码:539 / +
页数:13
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