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

doi:10.1016/j.cmet.2017.08.005

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 journal › Article

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 language	English (US)
Pages (from-to)	539-546.e5
Journal	Cell Metabolism
Volume	26
Issue number	3
DOIs	https://doi.org/10.1016/j.cmet.2017.08.005
State	Published - 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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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

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

In: Cell Metabolism, Vol. 26, No. 3, 05.09.2017, p. 539-546.e5.

Research output: Contribution to journal › Article

Roberts, MN, Wallace, MA, Tomilov, A, Zhou, Z, Marcotte, GR, Tran, D, Perez, G, Gutierrez-Casado, E, Koike, S, Knotts, TA, Imai, D , Griffey, SM , Kim, K , Hagopian, K , Haj, F , Baar, K , Cortopassi, GA , Ramsey, JJ & Lopez-Dominguez, JA 2017, 'A Ketogenic Diet Extends Longevity and Healthspan in Adult Mice', Cell Metabolism, vol. 26, no. 3, pp. 539-546.e5. https://doi.org/10.1016/j.cmet.2017.08.005

Roberts, Megan N. ; Wallace, Marita A. ; Tomilov, Alexey ; Zhou, Zeyu ; Marcotte, George R. ; Tran, Dianna ; Perez, Gabriella ; Gutierrez-Casado, Elena ; Koike, Shinichiro ; Knotts, Trina A. ; Imai, Denise ; Griffey, Stephen M ; Kim, Kyoungmi ; Hagopian, Kevork ; Haj, Fawaz ; Baar, Keith ; Cortopassi, Gino A ; Ramsey, Jon J ; Lopez-Dominguez, Jose Alberto. / A Ketogenic Diet Extends Longevity and Healthspan in Adult Mice. In: Cell Metabolism. 2017 ; Vol. 26, No. 3. pp. 539-546.e5.

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