A Ketogenic Diet Extends Longevity and Healthspan in Adult Mice

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

Research output: Contribution to journalArticle

84 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)539-546.e5
JournalCell Metabolism
Volume26
Issue number3
DOIs
StatePublished - Sep 5 2017

Keywords

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

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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  • Cite this

    Roberts, M. N., Wallace, M. A., Tomilov, A., Zhou, Z., Marcotte, G. R., Tran, D., Perez, G., Gutierrez-Casado, E., Koike, S., Knotts, T. A., Imai, D., Griffey, S. M., Kim, K., Hagopian, K., Haj, F., Baar, K., Cortopassi, G. A., Ramsey, J. J., & Lopez-Dominguez, J. A. (2017). A Ketogenic Diet Extends Longevity and Healthspan in Adult Mice. Cell Metabolism, 26(3), 539-546.e5. https://doi.org/10.1016/j.cmet.2017.08.005