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Ketogenic Diet Reduces Midlife Mortality and Improves Memory in Aging Mice
Open accessAbstract
Ketogenic diets recapitulate certain metabolic aspects of dietary restriction such as reliance on fatty acid metabolism and production of ketone bodies. We investigated whether an isoprotein ketogenic diet (KD) might, like dietary restriction, affect longevity and healthspan in C57BL/6 male mice. We find that Cyclic KD, KD alternated weekly with the Control diet to prevent obesity, reduces midlife mortality but does not affect maximum lifespan. A non-ketogenic high-fat diet (HF) fed similarly may have an intermediate effect on mortality. Cyclic KD improves memory performance in old age, while modestly improving composite healthspan measures. Gene expression analysis identifies downregulation of insulin, protein synthesis, and fatty acid synthesis pathways as mechanisms common to KD and HF. However, upregulation of PPARα target genes is unique to KD, consistent across tissues, and preserved in old age. In all, we show that a non-obesogenic ketogenic diet improves survival, memory, and healthspan in aging mice.
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“Several clinical studies have shown a positive effect of a ketogenic diet on patients with AD or mild cognitive impairment (MCI), consistent with preclinical results [87–91] (Table 1).”
From Role of diet and its effects on the gut microbiome in the pathophysiology of mental disorders (2022) · cites this paper as [88]
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Metadata
- Authors
- Newman, J. C., Covarrubias, A. J., Zhao, M., Yu, X., Gut, P., Ng, C.-P., Huang, Y., Haldar, S., & Verdin, E.
- Affiliations
- Gladstone Institutes (US)
- Buck Institute for Research on Aging (US)
- University of California, San Francisco (US)
- Corresponding author
- Verdin, Eric
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2017-09
- Volume
- 26
- Issue
- 3
- Pages
- 547-557.e8
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC5605815
- OpenAlex
- W2750998547
- Cited by
- 493
- References
- 43
- Citations by year
- 2026: 39 · 2025: 50 · 2024: 68 · 2023: 63 · 2022: 68 · 2021: 57 · 2020: 66 · 2019: 42 · 2018: 32 · 2017: 7
- FWCI
- 17.12
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH (P30NS065780, K08AG048354, R24DK085610)
- Gladstone Institutes
- Buck Institute
- Buck Impact Circle
- Larry L. Hillblom Foundation (2012-A-016-FEL)
- Glenn Foundation for Medical Research
- American Federation for Aging Research
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Physiology (medical) › Diet and metabolism studies
- Health Sciences › Medicine › Physiology (medical) › Dietary Effects on Health
- Keywords
- ketogenic diet, midlife mortality, healthspan, aging, memory, high-fat diet, PPARα, insulin signaling, protein synthesis, fatty acid synthesis, ketone bodies, dietary restriction, longevity, obesity prevention, C57BL/6 mice
- MeSH terms
- Aging, Animals, Fasting, Gene Expression Regulation, Liver, Male, Memory, Mice, Inbred C57BL, Mortality, PPAR alpha, Diet, Ketogenic, Diet, High-Fat
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