A Ketogenic Diet Extends Longevity and Healthspan in Adult Mice
Open accessAbstract
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.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
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 · see citing works
Object recognition test in mice
Leger, M., Quiedeville, A., Bouet, V., Haelewyn, B., Boulouard, M., Schumann-Bard, P., & Freret, T. (2013) · Nature Protocols · doi:10.1038/nprot.2013.155 · Cited by 1,357 · see citing works
Ketone bodies as signaling metabolites
Newman, J. C., & Verdin, E. (2014) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2013.09.002 · Cited by 966 · see citing works
Levine, M. E., Suarez, J. A., Brandhorst, S., Balasubramanian, P., Cheng, C.-W., Madia, F., Fontana, L., Mirisola, M. G., Guevara-Aguirre, J., Wan, J., et al. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.02.006 · Cited by 910 · see citing works
Solon-Biet, S. M., McMahon, A. C., Ballard, J. W. O., Ruohonen, K., Wu, L. E., Cogger, V. C., Warren, A., Huang, X., Pichaud, N., Melvin, R. G., et al. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.02.009 · Cited by 904 · see citing works
Brandhorst, S., Choi, I. Y., Wei, M., Cheng, C. W., Sedrakyan, S., Navarrete, G., Dubeau, L., Yap, L. P., Park, R., Vinciguerra, M., et al. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.05.012 · Cited by 850 · see citing works
Speakman, J. R., & Mitchell, S. E. (2011) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2011.07.001 · Cited by 769 · see citing works
Miller, R. A., Buehner, G., Chang, Y., Harper, J. M., Sigler, R. E., & Smith‐Wheelock, M. (2005) · Aging Cell · doi:10.1111/j.1474-9726.2005.00152.x · Cited by 734 · see citing works
Surwit, R. S., Feinglos, M. N., Rodin, J., Sutherland, A., Petro, A. E., Opara, E. C., Kuhn, C. M., & Rebuffe-Scrive, M. (1995) · Metabolism · doi:10.1016/0026-0495(95)90123-x · Cited by 618 · see citing works
Metformin, independent of AMPK, induces mTOR inhibition and cell-cycle arrest through REDD1
Ben Sahra, I., Regazzetti, C., Robert, G., Laurent, K., Le Marchand-Brustel, Y., Auberger, P., Tanti, J.-F., Giorgetti-Peraldi, S., & Bost, F. (2011) · Cancer Research · doi:10.1158/0008-5472.can-10-1769 · Cited by 616 · see citing works
Low methionine ingestion by rats extends life span.
Orentreich, N., Matias, J. R., Felice, A. D., & Zimmerman, J. (1993) · Journal of NutriLife · doi:10.1093/jn/123.2.269 · Cited by 608 · see citing works
Yuan, R., Tsaih, S., Petkova, S. B., de Evsikova, C. M., Xing, S., Marion, M. A., Bogue, M. A., Mills, K. D., Peters, L. L., Bult, C. J., et al. (2009) · Aging Cell · doi:10.1111/j.1474-9726.2009.00478.x · Cited by 414 · see citing works
Calorie restriction increases fatty acid synthesis and whole body fat oxidation rates
Bruss, M. D., Khambatta, C. F., Ruby, M. A., Aggarwal, I., & Hellerstein, M. K. (2009) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00524.2009 · Cited by 321 · see citing works
The ketogenic diet inhibits the mammalian target of rapamycin (mTOR) pathway
McDaniel, S. S., Rensing, N. R., Thio, L. L., Yamada, K. A., & Wong, M. L. (2011) · Epilepsia · doi:10.1111/j.1528-1167.2011.02981.x · Cited by 304 · see citing works
Calorie restriction alters mitochondrial protein acetylation
Schwer, B., Eckersdorff, M., Li, Y., Silva, J. C., Fermin, D., Kurtev, M. V., Giallourakis, C., Comb, M. J., Alt, F. W., & Lombard, D. B. (2009) · Aging Cell · doi:10.1111/j.1474-9726.2009.00503.x · Cited by 259 · cited 2× · see citing works
“, 2006), and protein acetylation is increased as described in previous CR studies (Schwer et al., 2009).”
Metabolic networks of longevity
Houtkooper, R. H., Williams, R. W., & Auwerx, J. (2010) · Cell · doi:10.1016/j.cell.2010.06.029 · Cited by 217 · see citing works
Early detection of cognitive deficits in the 3xTg-AD mouse model of Alzheimer's disease
Stover, K. R., Campbell, M. A., Winssen, C. M. V., & Brown, R. E. (2015) · Behavioural Brain Research · doi:10.1016/j.bbr.2015.04.012 · Cited by 203 · see citing works
Sharples, A. P., Hughes, D. C., Deane, C. S., Saini, A. S., Selman, C., & Stewart, C. E. (2015) · Aging Cell · doi:10.1111/acel.12342 · Cited by 200 · see citing works
Influence of Protein Under- and Overnutrition on Spontaneous Tumor Prevalence in the Rat
Ross, M. H., & Bras, G. (1973) · Journal of Nutrition · doi:10.1093/jn/103.7.944 · Cited by 148 · see citing works
Battery of behavioral tests in mice that models age-associated changes in human motor function
Justice, J. N., Carter, C. S., Beck, H. J., Gioscia‐Ryan, R. A., McQueen, M. B., Enoka, R. M., & Seals, D. R. (2013) · AGE · doi:10.1007/s11357-013-9589-9 · Cited by 125 · see citing works
Klement, R. J., & Champ, C. E. (2014) · Cancer and Metastasis Reviews · doi:10.1007/s10555-014-9495-3 · Cited by 112 · see citing works
The life‐extending effect of dietary restriction requires F oxo3 in mice
Shimokawa, I., Komatsu, T., Hayashi, N., Kim, S., Kawata, T., Park, S., Hayashi, H., Yamaza, H., Chiba, T., & Mori, R. (2015) · Aging Cell · doi:10.1111/acel.12340 · Cited by 108 · see citing works
Douris, N., Melman, T., Pecherer, J. M., Pissios, P., Flier, J. S., Cantley, L. C., Locasale, J. W., & Maratos–Flier, E. (2015) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2015.07.009 · Cited by 101 · see citing works
Rousselet, E., Joubert, C., Callebert, J., Parain, K., Tremblay, L., Orieux, G., Launay, J., Cohen‐Salmon, C., & Hirsch, É. C. (2003) · Neurobiology of Disease · doi:10.1016/s0969-9961(03)00108-6 · Cited by 98 · see citing works
Caloric restriction in C57BL/6J mice mimics therapeutic fasting in humans
Mahoney, L. B., Denny, C. A., & Seyfried, T. N. (2006) · Lipids in Health and Disease · doi:10.1186/1476-511x-5-13 · Cited by 98 · see citing works
Schupp, M., Chen, F., Briggs, E. R., Rao, S. J., Pelzmann, H. J., Pessentheiner, A. R., Bogner‐Strauß, J. G., Lazar, M. A., Baldwin, D. A., & Prokesch, A. (2013) · BMC Genomics · doi:10.1186/1471-2164-14-758 · Cited by 96 · see citing works
Changes in behaviors of male C57BL/6J mice across adult life span and effects of dietary restriction
Fahlström, A., Zeberg, H., & Ulfhake, B. (2011) · AGE · doi:10.1007/s11357-011-9320-7 · Cited by 72 · see citing works
Acetoacetate Accelerates Muscle Regeneration and Ameliorates Muscular Dystrophy in Mice
Zou, X., Meng, J., Li, L., Han, W., Li, C., Zhong, R., Miao, X., Cai, J. C., Zhang, Y., & Zhu, D. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.676510 · Cited by 69 · see citing works
Meidenbauer, J. J., Ta, N. L., & Seyfried, T. N. (2014) · Nutrition & Metabolism · doi:10.1186/1743-7075-11-23 · Cited by 66 · see citing works
Differential effects of dietary caloric and protein restriction in the aging rat
Davis, T. A., Bales, C. W., & Beauchene, R. E. (1983) · Experimental Gerontology · doi:10.1016/0531-5565(83)90021-9 · Cited by 65 · see citing works
Methionine and choline regulate the metabolic phenotype of a ketogenic diet
Pissios, P., Hong, S., Kennedy, A. R., Prasad, D., Liu, F., & Maratos–Flier, E. (2013) · Molecular Metabolism · doi:10.1016/j.molmet.2013.07.003 · Cited by 61 · see citing works
Calorie Restriction Does Not Increase Short-term or Long-term Protein Synthesis
Miller, B. F., Robinson, M. M., Reuland, D. J., Drake, J. C., Peelor, F. F., Bruss, M. D., Hellerstein, M. K., & Hamilton, K. L. (2012) · The Journals of Gerontology Series A · doi:10.1093/gerona/gls219 · Cited by 56 · see citing works
Roberts, M. D., Holland, A. M., Kephart, W. C., Mobley, C. B., Mumford, P. W., Lowery, R. P., Fox, C. D., McCloskey, A. E., Shake, J. J., Mesquita, P. H. C., et al. (2015) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00837.2015 · Cited by 28 · see citing works
Self-citationEffect of Protein Nutrition on Growth and Life Span in the Rat
Nakagawa, I., & Masana, Y. (1971) · Journal of Nutrition · doi:10.1093/jn/101.5.613 · Cited by 27 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Association between insulin resistance and the development of cardiovascular disease
Ormazábal, V., Nair, S., Elfeky, O. W. M., Aguayo, C. R., Salomón, C., & Zuñiga, F. A. (2018) · Cardiovascular Diabetology · doi:10.1186/s12933-018-0762-4 · Cited by 2,344 · see citing works
From 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 · see citing works
The gut microbiota at the intersection of diet and human health
Gentile, C. L., & Weir, T. L. (2018) · Science · doi:10.1126/science.aau5812 · Cited by 1,049 · see citing works
The metabolic roots of senescence: mechanisms and opportunities for intervention
Wiley, C. D., & Campisi, J. (2021) · Nature Metabolism · doi:10.1038/s42255-021-00483-8 · Cited by 691 · see citing works
The aetiology and molecular landscape of insulin resistance
James, D. E., Stöckli, J., & Birnbaum, M. J. (2021) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-021-00390-6 · Cited by 701 · see citing works
Francesco, A. D., Germanio, C. D., Bernier, M., & de Cabo, R. (2018) · Science · doi:10.1126/science.aau2095 · Cited by 497 · see citing works
The evolving metabolic landscape of chromatin biology and epigenetics
Dai, Z., Ramesh, V., & Locasale, J. W. (2020) · Nature Reviews Genetics · doi:10.1038/s41576-020-0270-8 · Cited by 494 · see citing works
The quest to slow ageing through drug discovery
Partridge, L., Fuentealba, M., & Kennedy, B. K. (2020) · Nature Reviews Drug Discovery · doi:10.1038/s41573-020-0067-7 · Cited by 468 · see citing works
The ageing epigenome and its rejuvenation
Zhang, W., Qu, J. T., Liu, G., & Belmonte, J. C. I. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0204-5 · Cited by 472 · see citing works
Ketogenic diet in the treatment of cancer – Where do we stand?
Weber, D. D., Aminzadeh-Gohari, S., Tulipan, J., Catalano, L., Feichtinger, R. G., & Kofler, B. (2019) · Molecular Metabolism · doi:10.1016/j.molmet.2019.06.026 · Cited by 464 · see citing works
The role of lipid metabolism in aging, lifespan regulation, and age‐related disease
Johnson, A. A., & Stolzing, A. (2019) · Aging Cell · doi:10.1111/acel.13048 · Cited by 452 · see citing works
Dominguez, L. J., Veronese, N., Vernuccio, L., Catanese, G., Inzerillo, F., Salemi, G., & Barbagallo, M. (2021) · Nutrients · doi:10.3390/nu13114080 · Cited by 433 · see citing works
Hallberg, S. J., McKenzie, A. L., Williams, P. T., Bhanpuri, N. H., Peters, A. L., Campbell, W. W., Hazbun, T. L., Volk, B. M., McCarter, J. P., Phinney, S. D., et al. (2018) · Diabetes Therapy · doi:10.1007/s13300-018-0373-9 · Cited by 406 · see citing works
Zhu, H., Bi, D., Zhang, Y., Kong, C., Du, J., Wu, X., Wei, Q., & Qin, H. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00831-w · Cited by 412 · see citing works
Time-Restricted Eating to Prevent and Manage Chronic Metabolic Diseases
Chaix, A., Manoogian, E. N. C., Melkani, G. C., & Panda, S. (2019) · Annual Review of Nutrition · doi:10.1146/annurev-nutr-082018-124320 · Cited by 402 · see citing works
Targeting the biology of aging with mTOR inhibitors
Mannick, J. B., & Lamming, D. W. (2023) · Nature Aging · doi:10.1038/s43587-023-00416-y · Cited by 372 · see citing works
Tomita, I., Kume, S., Sugahara, S., Osawa, N., Yamahara, K., Yasuda-Yamahara, M., Takeda, N., Chin-Kanasaki, M., Kaneko, T., Mayoux, E., et al. (2020) · Cell Metabolism · doi:10.1016/j.cmet.2020.06.020 · Cited by 376 · see citing works
Targeting autophagy in obesity: from pathophysiology to management
Zhang, Y., Sowers, J. R., & Ren, J. (2018) · Nature Reviews Endocrinology · doi:10.1038/s41574-018-0009-1 · Cited by 338 · see citing works
Nutrition, longevity and disease: From molecular mechanisms to interventions
Longo, V. D., & Anderson, R. M. (2022) · Cell · doi:10.1016/j.cell.2022.04.002 · Cited by 342 · see citing works
Mammalian/mechanistic target of rapamycin (mTOR) complexes in neurodegeneration
Querfurth, H., & Lee, H.-K. (2021) · Molecular Neurodegeneration · doi:10.1186/s13024-021-00428-5 · Cited by 288 · see citing works
Daily Fasting Improves Health and Survival in Male Mice Independent of Diet Composition and Calories
Mitchell, S. J., Bernier, M., Mattison, J. A., Aon, M. A., Kaiser, T. A., Anson, R. M., Ikeno, Y., Anderson, R. M., Ingram, D. K., & de Cabo, R. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.08.011 · Cited by 305 · see citing works
Molecular mechanisms of aging and anti-aging strategies
Li, Y., Tian, X., Luo, J., Bao, T., Wang, S., & Wu, X. (2024) · Cell Communication and Signaling · doi:10.1186/s12964-024-01663-1 · Cited by 333 · see citing works
Caprio, M., Infante, M., Moriconi, E., Armani, A., Fabbri, A., Mantovani, G., Mariani, S., Lubrano, C., Poggiogalle, E., Migliaccio, S., et al. (2019) · Journal of Endocrinological Investigation · doi:10.1007/s40618-019-01061-2 · Cited by 283 · see citing works
Chriett, S., Dąbek, A., Wojtala, M., Vidal, H., Balcerczyk, A., & Pirola, L. (2019) · Scientific Reports · doi:10.1038/s41598-018-36941-9 · Cited by 265 · see citing works
Importance of circadian timing for aging and longevity
Acosta-Rodríguez, V. A., Rijo‐Ferreira, F., Green, C. B., & Takahashi, J. S. (2021) · Nature Communications · doi:10.1038/s41467-021-22922-6 · Cited by 249 · see citing works
Inflammageing and metaflammation: The yin and yang of type 2 diabetes
Prattichizzo, F., Nigris, V. D., Spiga, R., Mancuso, E., Sala, L. L., Antonicelli, R., Testa, R., Procopio, A. D., Olivieri, F., & Ceriello, A. (2017) · Ageing Research Reviews · doi:10.1016/j.arr.2017.10.003 · Cited by 249 · see citing works
Aging and Rejuvenation of Neural Stem Cells and Their Niches
Navarro Negredo, P., Yeo, R. W., & Brunet, A. (2020) · Cell Stem Cell · doi:10.1016/j.stem.2020.07.002 · Cited by 246 · see citing works
Obesity and aging: Molecular mechanisms and therapeutic approaches
Santos, A. L., & Sinha, S. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101268 · Cited by 240 · see citing works
Low-Carb and Ketogenic Diets in Type 1 and Type 2 Diabetes
Bolla, A. M., Caretto, A., Laurenzi, A., Scavini, M., & Piemonti, L. (2019) · Nutrients · doi:10.3390/nu11050962 · Cited by 226 · see citing works
Diet strategies for promoting healthy aging and longevity: An epidemiological perspective
Hu, F. B. (2023) · Journal of Internal Medicine · doi:10.1111/joim.13728 · Cited by 220 · see citing works
The ups and downs of caloric restriction and fasting: from molecular effects to clinical application
Hofer, S. J., Carmona‐Gutiérrez, D., Mueller, M. I., & Madeo, F. (2021) · EMBO Molecular Medicine · doi:10.15252/emmm.202114418 · Cited by 207 · see citing works
Autophagy in aging and longevity
Wong, S. Q., Kumar, A. V., Mills, J., & Lapierre, L. R. (2019) · Human Genetics · doi:10.1007/s00439-019-02031-7 · Cited by 204 · see citing works
Kong, C., Yan, X., Liu, Y., Huang, L., Zhu, Y., He, J., Gao, R., Kalady, M. F., Goel, A., Qin, H., et al. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00549-9 · Cited by 201 · see citing works
Miller, V. J., Villamena, F. A., & Volek, J. S. (2018) · Journal of Nutrition and Metabolism · doi:10.1155/2018/5157645 · Cited by 200 · see citing works
Immune Clearance of Senescent Cells to Combat Ageing and Chronic Diseases
Song, P., An, J., & Zou, M.-H. (2020) · Cells · doi:10.3390/cells9030671 · Cited by 198 · see citing works
“In addition, β-hydroxybutyrate (β-HB) may mediate the effect of a ketogenic diet [113,114], intermittent fasting [115] or exercise [116] on healthspan extension or neuroregeneration because of its anti-inflammation [117], inhibition of vascular cell senescence [118] or immune activation by the formation and maintenanc…”
BackgroundA Ketogenic Diet Improves Mitochondrial Biogenesis and Bioenergetics via the PGC1α-SIRT3-UCP2 Axis
Hasan‐Olive, M. M., Lauritzen, K. H., Ali, M., Rasmussen, L. J., Storm‐Mathisen, J., & Bergersen, L. H. (2018) · Neurochemical Research · doi:10.1007/s11064-018-2588-6 · Cited by 182 · see citing works
Acetyl-CoA Metabolism and Histone Acetylation in the Regulation of Aging and Lifespan
Bradshaw, P. (2021) · Antioxidants · doi:10.3390/antiox10040572 · Cited by 162 · see citing works
Dietary regulation in health and disease
Wu, Q., Gao, Z., Yu, X., & Wang, P. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01104-w · Cited by 182 · see citing works
Cytoplasmic and Mitochondrial NADPH-Coupled Redox Systems in the Regulation of Aging
Bradshaw, P. C. (2019) · Nutrients · doi:10.3390/nu11030504 · Cited by 178 · see citing works
Salt-Responsive Metabolite, β-Hydroxybutyrate, Attenuates Hypertension
Chakraborty, S., Galla, S., Cheng, X., Yeo, J. Y., Mell, B., Singh, V., Yeoh, B. S., Saha, P., Mathew, A. V., Vijay–Kumar, M., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.09.058 · Cited by 176 · see citing works
The central moTOR of metabolism
Simcox, J., & Lamming, D. W. (2022) · Developmental Cell · doi:10.1016/j.devcel.2022.02.024 · Cited by 162 · see citing works
Ketogenesis activates metabolically protective γδ T cells in visceral adipose tissue
Goldberg, E. L., Shchukina, I., Asher, J. L., Sidorov, S., Artyomov, M. N., & Dixit, V. D. (2020) · Nature Metabolism · doi:10.1038/s42255-019-0160-6 · Cited by 162 · see citing works
Grajeda-Iglesias, C., Durand, S., Daillère, R., Iribarren, K., Lemaitre, F., Derosa, L., Aprahamian, F., Bossut, N., Nirmalathasan, N., Madeo, F., et al. (2021) · Aging · doi:10.18632/aging.202739 · Cited by 161 · see citing works
Turning back time with emerging rejuvenation strategies
Mahmoudi, S., Xu, L., & Brunet, A. (2018) · Nature Cell Biology · doi:10.1038/s41556-018-0206-0 · Cited by 163 · see citing works
p53 β-hydroxybutyrylation attenuates p53 activity
Liu, K., Li, F., Sun, Q., Lin, N., Han, H., You, K., Tian, F., Mao, Z., Li, T., Tong, T., et al. (2019) · Cell Death and Disease · doi:10.1038/s41419-019-1463-y · Cited by 149 · see citing works
Ketone Body, 3-Hydroxybutyrate: Minor Metabolite - Major Medical Manifestations
Møller, N. (2020) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgaa370 · Cited by 143 · see citing works
Ketogenesis impact on liver metabolism revealed by proteomics of lysine β-hydroxybutyrylation
Koronowski, K. B., Greco, C. M., Huang, H., Kim, J., Fribourgh, J. L., Crosby, P., Mathur, L., Ren, X., Partch, C. L., Jang, C., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109487 · Cited by 141 · see citing works
Antiaging diets: Separating fact from fiction
Lee, M. B., Hill, C. M., Bitto, A., & Kaeberlein, M. R. (2021) · Science · doi:10.1126/science.abe7365 · Cited by 143 · see citing works
Mukherjee, P., Augur, Z. M., Li, M., Hill, C., Greenwood, B. P., Domin, M. A., Kondakci, G., Narain, N. R., Kiebish, M. A., Bronson, R. T., et al. (2019) · Communications Biology · doi:10.1038/s42003-019-0455-x · Cited by 140 · see citing works
β-hydroxybutyrate and its metabolic effects on age-associated pathology
Han, Y., Ramprasath, T., & Zou, M. (2020) · Experimental & Molecular Medicine · doi:10.1038/s12276-020-0415-z · Cited by 137 · see citing works
Control of immunity via nutritional interventions
Collins, N., & Belkaid, Y. (2022) · Immunity · doi:10.1016/j.immuni.2022.01.004 · Cited by 130 · see citing works
Amino acids in the regulation of aging and aging-related diseases
Canfield, C.-A. E., & Bradshaw, P. C. (2019) · Translational Medicine of Aging · doi:10.1016/j.tma.2019.09.001 · Cited by 133 · see citing works
β-hydroxybutyrate as an Anti-Aging Metabolite
Wang, L. Y., Chen, P., & Xiao, W. (2021) · Nutrients · doi:10.3390/nu13103420 · Cited by 133 · see citing works
Ketone body receptor GPR43 regulates lipid metabolism under ketogenic conditions
Miyamoto, J., Ohue‐Kitano, R., Mukouyama, H., Nishida, A., Watanabe, K., Igarashi, M., Irie, J., Tsujimoto, G., Satoh‐Asahara, N., Itoh, H., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1912573116 · Cited by 133 · see citing works
Gut microbiota controlling radiation-induced enteritis and intestinal regeneration
Moraitis, I., Guiu, J., & Rubert, J. (2023) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2023.05.006 · Cited by 128 · see citing works
The road ahead for health and lifespan interventions
Gonzalez-Freire, M., Diaz-Ruiz, A., Hauser, D., Martinez-Romero, J., Ferrucci, L., Bernier, M., & de Cabo, R. (2020) · Ageing Research Reviews · doi:10.1016/j.arr.2020.101037 · Cited by 118 · see citing works
García-Rodríguez, D., & Giménez-Cassina, A. (2021) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2021.732120 · Cited by 123 · see citing works
Prattichizzo, F., Nigris, V. D., Micheloni, S., Sala, L. L., & Ceriello, A. (2018) · Diabetes Obesity and Metabolism · doi:10.1111/dom.13488 · Cited by 116 · see citing works
Carbotoxicity—Noxious Effects of Carbohydrates
Kroemer, G., López-Otı́n, C., Madeo, F., & de Cabo, R. (2018) · Cell · doi:10.1016/j.cell.2018.07.044 · Cited by 117 · see citing works
Ketogenic diet and chemotherapy combine to disrupt pancreatic cancer metabolism and growth
Yang, L., TeSlaa, T. A., Ng, S., Nofal, M., Wang, L., Lan, T., Zeng, X., Cowan, A. J., McBride, M. J., Lu, W., et al. (2022) · Med · doi:10.1016/j.medj.2021.12.008 · Cited by 117 · see citing works
Ketogenic Diet: A New Light Shining on Old but Gold Biochemistry
Longo, R., Peri, C., Cricrì, D., Coppi, L., Caruso, D., Mitro, N., Fabiani, E. D., & Crestani, M. (2019) · Nutrients · doi:10.3390/nu11102497 · Cited by 117 · see citing works
Hernandez, A. R., Hernandez, C. M., Campos, K., Truckenbrod, L., Federico, Q., Moon, B., McQuail, J. A., Maurer, A. P., Bizon, J. L., & Burke, S. N. (2018) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2018.00391 · Cited by 111 · see citing works
Hoong, C. W. S., & Chua, M. W. J. (2021) · Endocrinology · doi:10.1210/endocr/bqab079 · Cited by 112 · see citing works
Lithocholic acid phenocopies anti-ageing effects of calorie restriction
Qu, Q., Chen, Y., Wang, Y., Long, S., Wang, W., Yang, H.-Y., Li, M., Tian, X., Wei, X., Liu, Y., et al. (2024) · Nature · doi:10.1038/s41586-024-08329-5 · Cited by 117 · see citing works
Cardiac ketone body metabolism
Kadir, A. A., Clarke, K., & Evans, R. D. (2020) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2020.165739 · Cited by 108 · see citing works
Green, C. L., Pak, H. H., Richardson, N. E., Flores, V., Yu, D., Tomasiewicz, J. L., Dumas, S. N., Kredell, K., Fan, J. W., Kirsh, C., et al. (2022) · Cell Metabolism · doi:10.1016/j.cmet.2021.12.018 · Cited by 99 · see citing works
Hwang, C. Y., Choe, W., Yoon, K., Ha, J., Kim, S. S., Yeo, E., & Kang, I. (2022) · Nutrients · doi:10.3390/nu14224932 · Cited by 105 · see citing works
Ketone-Based Metabolic Therapy: Is Increased NAD+ a Primary Mechanism?
Elamin, M., Ruskin, D. N., Masino, S. A., & Sacchetti, P. (2017) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2017.00377 · Cited by 101 · see citing works
Grandl, G., Straub, L., Rudigier, C., Arnold, M., Wueest, S., Konrad, D., & Wolfrum, C. (2018) · The Journal of Physiology · doi:10.1113/jp275173 · Cited by 97 · see citing works
The ketogenic diet preserves skeletal muscle with aging in mice
Wallace, M. A., Aguirre, N. W., Marcotte, G. R., Marshall, A. G., Baehr, L. M., Hughes, D. C., Hamilton, K. L., Roberts, M. N., Lopez‐Dominguez, J. A., Miller, B. F., et al. (2021) · Aging Cell · doi:10.1111/acel.13322 · Cited by 93 · see citing works
Self-citationSex differences in response to short-term high fat diet in mice
Huang, K.-P., Ronveaux, C. C., Knotts, T. A., Rutkowsky, J. M., Ramsey, J. J., & Raybould, H. E. (2020) · Physiology & Behavior · doi:10.1016/j.physbeh.2020.112894 · Cited by 92 · see citing works
Self-citationMihaylova, M. M., Chaix, A., Delibegović, M., Ramsey, J. J., Bass, J. T., Melkani, G. C., Singh, R., Chen, Z., Ja, W. W., Shirasu-Hiza, M., et al. (2023) · Cell Metabolism · doi:10.1016/j.cmet.2023.06.008 · Cited by 91 · see citing works
Self-citationRole of diet and exercise in aging, Alzheimer’s disease, and other chronic diseases
Khemka, S., Reddy, A., Garcia, R. I., Jacobs, M., Reddy, R. P., Roghani, A. K., Pattoor, V., Basu, T., Sehar, U., & Reddy, P. H. (2023) · Ageing Research Reviews · doi:10.1016/j.arr.2023.102091 · Cited by 88 · see citing works
Targeting metabolic pathways for extension of lifespan and healthspan across multiple species
Parkhitko, A. A., Filine, E., Mohr, S. E., Moskalev, A., & Perrimon, N. (2020) · Ageing Research Reviews · doi:10.1016/j.arr.2020.101188 · Cited by 90 · see citing works
Ketogenic diet induces p53-dependent cellular senescence in multiple organs
Wei, S., Schell, J. R., Chocrón, E. S., Varmazyad, M., Xu, G., Chen, W. H., Martinez, G. M., Dong, F. F., Sreenivas, P., Trevino, R., et al. (2024) · Science Advances · doi:10.1126/sciadv.ado1463 · Cited by 89 · see citing works
Ketone Bodies Attenuate Wasting in Models of Atrophy
Koutnik, A., Poff, A., Ward, N. P., Deblasi, J., Soliven, M. A., Romero, M., Roberson, P. A., Fox, C. D., Roberts, M., & D'Agostino, D. (2020) · Journal of Cachexia, Sarcopenia and Muscle · doi:10.1002/jcsm.12554 · Cited by 64 · see citing works
Self-citationCaloric Restriction Engages Hepatic RNA Processing Mechanisms in Rhesus Monkeys
Rhoads, T. W., Burhans, M. S., Chen, V. B., Hutchins, P. D., Rush, M. J. P., Clark, J. P., Stark, J. L., McIlwain, S. J., Eghbalnia, H. R., Pavelec, D. M., et al. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.01.014 · Cited by 81 · see citing works
Ketogenic Diets and Exercise Performance
Harvey, K. L., Holcomb, L. E., & Kolwicz, S. C. (2019) · Nutrients · doi:10.3390/nu11102296 · Cited by 84 · see citing works
Targeting Cell Senescence and Senolytics: Novel Interventions for Age-Related Endocrine Dysfunction
Suda, M., Paul, K. H., Tripathi, U., Minamino, T., Tchkonia, T., & Kirkland, J. L. (2024) · Endocrine Reviews · doi:10.1210/endrev/bnae010 · Cited by 81 · see citing works
Antiaging effects of bioactive molecules isolated from plants and fungi
Martel, J., Ojcius, D. M., Ko, Y., Chang, C., & Young, J. D. (2019) · Medicinal Research Reviews · doi:10.1002/med.21559 · Cited by 79 · see citing works
Dietary interventions and precision nutrition in cancer therapy
Martínez-Garay, C., & Djouder, N. (2023) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2023.04.004 · Cited by 79 · see citing works
Benjamin, D. I., Both, P., Benjamin, J. S., Nutter, C. W., Tan, J. H., Kang, J., Machado, L. A., Klein, J. D. D., de Morree, A., Kim, S., et al. (2022) · Cell Metabolism · doi:10.1016/j.cmet.2022.04.012 · Cited by 79 · see citing works
Ketogenic diet reshapes cancer metabolism through lysine β-hydroxybutyrylation
Qin, J., Huang, X., Gou, S., Zhang, S., Gou, Y., Zhang, Q., Chen, H., Sun, L., Chen, M., Liu, D., et al. (2024) · Nature Metabolism · doi:10.1038/s42255-024-01093-w · Cited by 77 · see citing works
Investigating Ketone Bodies as Immunometabolic Countermeasures against Respiratory Viral Infections
Stubbs, B. J., Koutnik, A. P., Goldberg, E. L., Upadhyay, V., Turnbaugh, P. J., Verdin, E., & Newman, J. C. (2020) · Med · doi:10.1016/j.medj.2020.06.008 · Cited by 71 · see citing works
Guo, Y., Zhang, C., Shang, F., Luo, M., You, Y., Zhai, Q., Xia, Y., & Suxin, L. (2020) · Aging and Disease · doi:10.14336/ad.2019.0510 · Cited by 75 · see citing works
Fasting and rapamycin: diabetes versus benevolent glucose intolerance
Blagosklonny, M. V. (2019) · Cell Death & Disease · doi:10.1038/s41419-019-1822-8 · Cited by 74 · see citing works
Nutrition, metabolism, and epigenetics: pathways of circadian reprogramming
Sato, T., & Sassone‐Corsi, P. (2022) · EMBO Reports · doi:10.15252/embr.202152412 · Cited by 74 · see citing works
Guo, Y., Wang, Z., Qin, X., Xu, J., Hou, Z., Yang, H., Mao, X., Xing, W., Li, X., Zhang, X., et al. (2018) · Cardiovascular Research · doi:10.1093/cvr/cvy052 · Cited by 73 · see citing works
The role of diet in preventing and reducing cognitive decline
Angeloni, C., Businaro, R., & Vauzour, D. (2020) · Current Opinion in Psychiatry · doi:10.1097/yco.0000000000000605 · Cited by 70 · see citing works
Dietary natural products as epigenetic modifiers in aging-associated inflammation and disease
Evans, L. W., Stratton, M. S., & Ferguson, B. S. (2020) · Natural Product Reports · doi:10.1039/c9np00057g · Cited by 70 · see citing works
Effects of ketogenic diet and ketone bodies on the cardiovascular system: Concentration matters
Nasser, S., Vialichka, V., Biesiekierska, M., Balcerczyk, A., & Pirola, L. (2020) · World Journal of Diabetes · doi:10.4239/wjd.v11.i12.584 · Cited by 69 · see citing works
An isocaloric moderately high-fat diet extends lifespan in male rats and Drosophila
Shi, D., Han, T., Chu, X., Lu, H., Yang, X. Y., Zi, T., Zhao, Y., Wang, X., Liu, Z., Ruan, J., et al. (2021) · Cell Metabolism · doi:10.1016/j.cmet.2020.12.017 · Cited by 68 · see citing works
Strong, R., Miller, R. A., Cheng, C. J. A., Nelson, J. F., Gelfond, J., Allani, S. K., Diaz, V., Dorigatti, A. O., Dorigatti, J. D., Fernández, E., et al. (2022) · Aging Cell · doi:10.1111/acel.13724 · Cited by 67 · see citing works
Extended Ketogenic Diet and Physical Training Intervention in Military Personnel
LaFountain, R. A., Miller, V. J., Barnhart, E. C., Hyde, P. N., Crabtree, C. D., McSwiney, F. T., Beeler, M. K., Buga, A., Sapper, T. N., Short, J. A., et al. (2019) · Military Medicine · doi:10.1093/milmed/usz046 · Cited by 71 · see citing works
Kovács, Z., Brunner, B., & Ari, C. (2021) · Nutrients · doi:10.3390/nu13072197 · Cited by 67 · see citing works
Ketone bodies as epigenetic modifiers
Ruan, H., & Crawford, P. A. (2018) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/mco.0000000000000475 · Cited by 66 · see citing works
Yang, Z., Mi, J., Wang, Y., Xue, L., Liu, J., Fan, M., Zhang, D., Wang, L., Qian, H., & Li, Y. (2021) · Nutrition · doi:10.1016/j.nut.2021.111230 · Cited by 65 · see citing works
Fan, S., Lin, C., Wei, Y., Yeh, S., Tsai, Y., Lee, A. C., Lin, W., & Wang, P. (2021) · Aging Cell · doi:10.1111/acel.13510 · Cited by 65 · see citing works
Lucente, J. D., Persico, G., Zhou, Z., Jin, L., Ramsey, J. J., Rutkowsky, J. M., Montgomery, C. B., Tomilov, A. A., Kim, K., Giorgio, M., et al. (2024) · Communications Biology · doi:10.1038/s42003-024-05860-z · Cited by 65 · see citing works
Self-citationCould very low-calorie ketogenic diets turn off low grade inflammation in obesity? Emerging evidence
Barrea, L., Caprio, M., Watanabe, M., Cammarata, G., Feraco, A., Muscogiuri, G., Verde, L., Colao, A., & Savastano, S. (2022) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2022.2054935 · Cited by 65 · see citing works
- 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
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2017-09
- Volume
- 26
- Issue
- 3
- Pages
- 539-546.e5
- ISSN
- 1550-4131 (ISSN-L)
- 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 · 2015: 1
- FWCI
- 29.73
- Type
- journal article
- Language
- en
- Update notices
- erratum (2018-05-01)
- Open access
- bronze
- doi.org
- Licence
- 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 › Diet and metabolism studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Physiology › 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review