The DOI matches its Crossref record; 42 of the 43 references it cites were found in a registry or an index.
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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Cites
Rapamycin fed late in life extends lifespan in genetically heterogeneous mice
Harrison, D. E., Strong, R., Sharp, Z. D., Nelson, J. F., Astle, C. M., Flurkey, K., Nadon, N. L., Wilkinson, J. E., Frenkel, K., Carter, C. S., et al. (2009) · Nature · doi:10.1038/nature08221 · Cited by 3,766
The ketone metabolite β-hydroxybutyrate blocks NLRP3 inflammasome-mediated inflammatory disease
Youm, Y.-H., Nguyen, K. Y., Grant, R. W., Goldberg, E. L., Bodogai, M., Kim, D., D'Agostino, D., Planavsky, N., Lupfer, C., Kanneganti, T. D., et al. (2015) · Nature Medicine · doi:10.1038/nm.3804 · Cited by 2,172
Suppression of Oxidative Stress by β-Hydroxybutyrate, an Endogenous Histone Deacetylase Inhibitor
Shimazu, T., Hirschey, M. D., Newman, J., He, W., Shirakawa, K., Le Moan, N., Grueter, C. A., Lim, H., Saunders, L. R., Stevens, R. D., et al. (2013) · Science · doi:10.1126/science.1227166 · Cited by 1,777
Self-citationBadman, M. K., Pissios, P., Kennedy, A. R., Koukos, G., Flier, J. S., & Maratos-Flier, E. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.05.002 · Cited by 1,495
Metformin improves healthspan and lifespan in mice
Martin-Montalvo, A., Mercken, E. M., Mitchell, S. J., Palacios, H. H., Mote, P. L., Scheibye-Knudsen, M., Gomes, A. P., Ward, T. M., Minor, R. K., Blouin, M.-J., et al. (2013) · Nature Communications · doi:10.1038/ncomms3192 · Cited by 1,445
Impact of intermittent fasting on health and disease processes
Mattson, M. P., Longo, V. D., & Harvie, M. (2017) · Ageing Research Reviews · doi:10.1016/j.arr.2016.10.005 · Cited by 1,187
Metabolic regulation of gene expression through histone acylations
Sabari, B. R., Zhang, D., Allis, C. D., & Zhao, Y. (2016) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2016.140 · Cited by 1,168
Kimura, I., Inoue, D., Maeda, T., Hara, T., Ichimura, A., Miyauchi, S., Kobayashi, M., Hirasawa, A., & Tsujimoto, G. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1016088108 · Cited by 1,106
Metformin as a tool to target aging
Barzilai, N., Crandall, J. P., Kritchevsky, S. B., & Espeland, M. A. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.05.011 · Cited by 1,096 · cited 2×
“…responsive networks has led to the first drug found to extend lifespan in healthy mammals— rapamycin (Harrison et al., 2009)—and the first candidate intervention for testing healthspan extension in a human clinical trial—metformin (Barzilai et al., 2016; Martin-Montalvo et al., 2013).”
BackgroundPeroxisome Proliferator-Activated Receptor Alpha Target Genes
Rakhshandehroo, M., Knoch, B., Müller, M., & Kersten, S. (2010) · PPAR Research · doi:10.1155/2010/612089 · Cited by 1,020
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“In this sense, recently it has been shown that cyclic ketone bodies preserve “young cardiac phenotype” in old mice [167].”
BackgroundFrom discoveries in ageing research to therapeutics for healthy ageing
Campisi, J., Kapahi, P., Lithgow, G. J., Melov, S., Newman, J. C., & Verdin, E. (2019) · Nature · doi:10.1038/s41586-019-1365-2 · Cited by 1,389
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Ketogenic Diets Alter the Gut Microbiome Resulting in Decreased Intestinal Th17 Cells
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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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