A Ketogenic Diet Extends Longevity and Healthspan in Adult Mice

Megan N Roberts; Marita A Wallace; Alexey A Tomilov; Zeyu Zhou; George R Marcotte; Dianna Tran; Gabriella Perez; Elena Gutierrez-Casado; Shinichiro Koike; Trina A Knotts; Denise M Imai; Stephen M Griffey; Kyoungmi Kim; Kevork Hagopian; Marissa Z McMackin; Fawaz G Haj; Keith Baar; Gino A Cortopassi; Jon J Ramsey; Jose Alberto Lopez-Dominguez

doi:10.1016/j.cmet.2017.08.005

A Ketogenic Diet Extends Longevity and Healthspan in Adult Mice

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

Authors

Megan N Roberts¹, Marita A Wallace², Alexey A Tomilov¹, Zeyu Zhou¹, George R Marcotte², Dianna Tran¹, Gabriella Perez¹, Elena Gutierrez-Casado³, Shinichiro Koike⁴, Trina A Knotts¹, Denise M Imai⁵, Stephen M Griffey⁵, Kyoungmi Kim⁶, Kevork Hagopian¹, Marissa Z McMackin¹, Fawaz G Haj⁴, Keith Baar⁷, Gino A Cortopassi¹, Jon J Ramsey⁸, Jose Alberto Lopez-Dominguez⁹

Affiliations

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.

MeSH terms

Acetylation
Adaptation, Physiological
Animals
Diet, Carbohydrate-Restricted
Diet, Ketogenic*
Health*
Longevity / physiology*
Male
Mechanistic Target of Rapamycin Complex 1 / metabolism
Mice, Inbred C57BL
Organ Specificity
Signal Transduction

Substances

Mechanistic Target of Rapamycin Complex 1

Abstract

MeSH terms

Substances

Grants and funding