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Cell Metab. 2017 Sep 5;26(3):539-546.e5. doi: 10.1016/j.cmet.2017.08.005.

A Ketogenic Diet Extends Longevity and Healthspan in Adult Mice.

Author information

1
Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, Davis, CA, USA.
2
Department of Neurobiology, Physiology, and Behavior, University of California, Davis, Davis, CA, USA.
3
Departamento de Biología Celular, Fisiología e Inmunología, Universidad de Córdoba, Córdoba, Spain.
4
Department of Nutrition, University of California, Davis, Davis, CA, USA.
5
Comparative Pathology Laboratory, School of Veterinary Medicine, University of California, Davis, Davis, CA, USA.
6
Department of Public Health Sciences, School of Medicine, University of California, Davis, Davis, CA, USA.
7
Department of Neurobiology, Physiology, and Behavior, University of California, Davis, Davis, CA, USA; Department of Physiology and Membrane Biology, School of Medicine, University of California, Davis, Davis, CA, USA.
8
Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, Davis, CA, USA. Electronic address: jjramsey@ucdavis.edu.
9
Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, Davis, CA, USA. Electronic address: jlopez-dominguez@buckinstitute.org.

Abstract

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.

KEYWORDS:

aging; beta-hydroxybutyrate; healthspan; ketogenic diet; ketone bodies; ketones; lifespan; longevity; low-carbohydrate diet; memory

PMID:
28877457
PMCID:
PMC5609489
DOI:
10.1016/j.cmet.2017.08.005
[Indexed for MEDLINE]
Free PMC Article

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