Cited by 515Diet and metabolism studiesGenetics, Aging, and Longevity in Model OrganismsDietary Effects on Health

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A Ketogenic Diet Extends Longevity and Healthspan in Adult Mice

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Roberts, Megan N., Wallace, Marita A., Tomilov, Alexey A., Zhou, Zeyu, Marcotte, George R., Tran, Dianna, Perez, Gabriella, Gutierrez-Casado, Elena, Koike, Shinichiro, Knotts, Trina A., Imai, Denise M., Griffey, Stephen M., Kim, Kyoungmi, Hagopian, Kevork, McMackin, Marissa Z., Haj, Fawaz G., Baar, Keith, Cortopassi, Gino A., Ramsey, Jon J., Lopez-Dominguez, Jose Alberto·2017·Cell Metabolism

DOI 10.1016/j.cmet.2017.08.005PMC PMC5609489

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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.

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Authors: Roberts, M. N., Wallace, M. A., Tomilov, A. A., Zhou, Z., Marcotte, G. R., Tran, D., Perez, G., Gutierrez-Casado, E., Koike, S., Knotts, T. A., Imai, D. M., Griffey, S. M., Kim, K., Hagopian, K., McMackin, M. Z., Haj, F. G., Baar, K., Cortopassi, G. A., Ramsey, J. J., & Lopez-Dominguez, J. A.
Affiliations: University of California, Davis (US)
Corresponding author: Ramsey, Jon J.
Lopez-Dominguez, Jose Alberto
ORCID: Wallace, Marita A.
Tomilov, Alexey A.
Zhou, Zeyu
Marcotte, George R.
Koike, Shinichiro
Knotts, Trina A.
Imai, Denise M.
Kim, Kyoungmi
McMackin, Marissa Z.
Haj, Fawaz G.
Baar, Keith
Cortopassi, Gino A.
Ramsey, Jon J.
Lopez-Dominguez, Jose Alberto
Venue: Cell Metabolism
Publisher: Elsevier BV
Published: 2017-09
Volume: 26
Issue: 3
Pages: 539-546.e5
ISSN: 1550-4131 (ISSN-L)
DOI: 10.1016/j.cmet.2017.08.005
PMC: PMC5609489
OpenAlex: W2750582921
Cited by: 514
References: 34
Citations by year: 2026: 33 · 2025: 63 · 2024: 67 · 2023: 68 · 2022: 67 · 2021: 66 · 2020: 65 · 2019: 43 · 2018: 32 · 2017: 7
FWCI: 29.73
Type: journal article
Language: en
Update notices: erratum (2018-05-01)
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 370 d)
Locations: Cell Metabolism (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Gredos (University of Salamanca) (acceptedVersion, other-oa)
Hispana (acceptedVersion, other-oa)
eScholarship (California Digital Library) (submittedVersion)
Funders: NIH (2P01AG025532)
UC Davis (U2CDK092993)
Topics: Health Sciences › Medicine › Physiology (medical) › Diet and metabolism studies
Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
Health Sciences › Medicine › Physiology (medical) › Dietary Effects on Health
Keywords: ketogenic diet, low-carbohydrate diet, longevity, healthspan, lifespan extension, aging, fatty acid beta-oxidation, glycolysis, protein acetylation, mTORC1 signaling, aged mice, physiological function
MeSH terms: Mechanistic Target of Rapamycin Complex 1, Acetylation, Adaptation, Physiological, Animals, Health, Longevity, Male, Mice, Inbred C57BL, Organ Specificity, Signal Transduction, Diet, Carbohydrate-Restricted, Diet, Ketogenic

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A Ketogenic Diet Extends Longevity and Healthspan in Adult Mice

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