Long-term moderate calorie restriction inhibits inflammation without impairing cell-mediated immunity: a randomized controlled trial in non-obese humans
Open accessAbstract
Calorie restriction (CR) inhibits inflammation and slows aging in many animal species, but in rodents housed in pathogen-free facilities, CR impairs immunity against certain pathogens. However, little is known about the effects of long-term moderate CR on immune function in humans. In this multi-center, randomized clinical trial to determine CR's effect on inflammation and cell-mediated immunity, 218 healthy non-obese adults (20-50 y), were assigned 25% CR (n=143) or an ad-libitum (AL) diet (n=75), and outcomes tested at baseline, 12, and 24 months of CR. CR induced a 10.4% weight loss over the 2-y period. Relative to AL group, CR reduced circulating inflammatory markers, including total WBC and lymphocyte counts, ICAM-1 and leptin. Serum CRP and TNF-α concentrations were about 40% and 50% lower in CR group, respectively. CR had no effect on the delayed-type hypersensitivity skin response or antibody response to vaccines, nor did it cause difference in clinically significant infections. In conclusion, long-term moderate CR without malnutrition induces a significant and persistent inhibition of inflammation without impairing key in vivo indicators of cell-mediated immunity. Given the established role of these pro-inflammatory molecules in the pathogenesis of multiple chronic diseases, these CR-induced adaptations suggest a shift toward a healthy phenotype.
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Calorie restriction in humans is associated with a substantial reduction in pro-inflammatory markers in the blood.
“In addition, calorie restriction in humans is associated with a substantial reduction in pro-inflammatory markers in the blood62.”
From Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty (2018) · cites this paper as [62]
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Longitudinal data analysis using generalized linear models
LIANG, K.-Y., & ZEGER, S. L. (1986) · Biometrika · doi:10.1093/biomet/73.1.13 · Cited by 18,550 · see citing works
McCullagh, P., & Nelder, J. A. (1989) · doi:10.1007/978-1-4899-3242-6 · Cited by 16,836 · see citing works
A Modified Poisson Regression Approach to Prospective Studies with Binary Data
Zou, G. (2004) · American Journal of Epidemiology · doi:10.1093/aje/kwh090 · Cited by 9,760 · see citing works
Adipose Expression of Tumor Necrosis Factor-α: Direct Role in Obesity-Linked Insulin Resistance
Hotamisligil, G. S., Shargill, N. S., & Spiegelman, B. M. (1993) · Science · doi:10.1126/science.7678183 · Cited by 7,518 · see citing works
Chronic Inflammation (Inflammaging) and Its Potential Contribution to Age-Associated Diseases
Franceschi, C., & Campisi, J. (2014) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/glu057 · Cited by 3,891 · see citing works
Extending Healthy Life Span—From Yeast to Humans
Fontana, L., Partridge, L., & Longo, V. D. (2010) · Science · doi:10.1126/science.1172539 · Cited by 3,023 · see citing works
Self-citationVisceral fat adipokine secretion is associated with systemic inflammation in obese humans
Fontana, L., Eagon, J. C., Trujillo, M. E., Scherer, P. E., & Klein, S. (2007) · Diabetes · doi:10.2337/db06-1656 · Cited by 1,417 · see citing works
Self-citationUnbalanced repeated-measures models with structured covariance matrices.
Jennrich, R., & Schluchter, M. (1986) · Biometrics · doi:10.2307/2530695 · Cited by 1,382 · see citing works
Kern, P. A., Saghizadeh, M., Ong, J. M., Bosch, R. J., Deem, R., & Simsolo, R. B. (1995) · Journal of Clinical Investigation · doi:10.1172/jci117899 · Cited by 1,305 · see citing works
Leptin regulates proinflammatory immune responses
Loffreda, S., Yang, S., Lin, H., Karp, C. L., Brengman, M. L., Wang, D., Klein, A. S., Bulkley, G. B., Bao, C., Noble, P. W., et al. (1998) · The FASEB Journal · doi:10.1096/fasebj.12.1.57 · Cited by 1,251 · see citing works
Statistical Models and Methods for Lifetime Data
Johnston, G. (2003) · Technometrics · doi:10.1198/tech.2003.s767 · Cited by 1,202 · see citing works
Nutrient sensing and inflammation in metabolic diseases
Hotamisligil, G. S., & Erbay, E. (2008) · Nature Reviews Immunology · doi:10.1038/nri2449 · Cited by 1,040 · see citing works
Adjusted P-Values for Simultaneous Inference
Wright, S. P. (1992) · Biometrics · doi:10.2307/2532694 · Cited by 1,026 · see citing works
Calorie restriction, SIRT1 and metabolism: understanding longevity
Bordone, L., & Guarente, L. (2005) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1616 · Cited by 1,021 · see citing works
Malnutrition and Infection: Complex Mechanisms and Global Impacts
Schaible, U. E., & Kaufmann, S. H. E. (2007) · PLoS Medicine · doi:10.1371/journal.pmed.0040115 · Cited by 958 · see citing works
The Critical Role of Metabolic Pathways in Aging
Barzilai, N., Huffman, D. M., Muzumdar, R. H., & Bartke, A. (2012) · Diabetes · doi:10.2337/db11-1300 · Cited by 803 · see citing works
Leptin regulates proinflammatory immune responses
Loffreda, S., Yang, S., Lin, H., et al. (1998) · The FASEB Journal · doi:10.1096/fsb2fasebj.12.1.57 · Cited by 527 · see citing works
Mitochondria—A Nexus for Aging, Calorie Restriction, and Sirtuins?
Guarente, L. (2008) · Cell · doi:10.1016/j.cell.2008.01.007 · Cited by 513 · see citing works
Ravussin, E., Redman, L. M., Rochon, J., Das, S. K., Fontana, L., Kraus, W. E., Romashkan, S., Williamson, D. A., Meydani, S. N., Villareal, D. T., et al. (2015) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/glv057 · Cited by 489 · see citing works
Self-citationLong-term caloric restriction ameliorates the decline in diastolic function in humans
Meyer, T. E., Kovács, S. J., Ehsani, A. A., Klein, S., Holloszy, J. O., & Fontana, L. (2006) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2005.08.069 · Cited by 383 · see citing works
Self-citation(1993) · PubMed · Cited by 330 · see citing works
Koenig, W. (2013) · International Journal of Cardiology · doi:10.1016/j.ijcard.2013.07.113 · Cited by 315 · see citing works
Leukocyte Count as a Predictor of Cardiovascular Events and Mortality in Postmenopausal Women
Margolis, K. L. (2005) · Archives of Internal Medicine · doi:10.1001/archinte.165.5.500 · Cited by 310 · see citing works
Molenberghs, G. (2005) · Journal of the American Statistical Association · doi:10.1198/jasa.2005.s24 · Cited by 267 · see citing works
Lam, Q. L. K., & Lu, L. (2007) · PubMed · Cited by 247 · see citing works
The role of inflammation in age-related disease
Howcroft, T. K., Campisi, J., Louis, G. B., Smith, M. T., Wise, B., Wyss-Coray, T., Augustine, A. D., McElhaney, J. E., Kohanski, R., & Sierra, F. (2013) · Aging · doi:10.18632/aging.100531 · Cited by 239 · see citing works
Inflammation and metabolic dysfunction: links to cardiovascular diseases
Taube, A., Schlich, R., Sell, H., Eckardt, K., & Eckel, J. (2012) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00907.2011 · Cited by 239 · see citing works
Delay of T cell senescence by caloric restriction in aged long-lived nonhuman primates
Messaoudi, I., Warner, J., Fischer, M. B., Park, B., Hill, B. J., Mattison, J. A., Lane, M. A., Roth, G. S., Ingram, D. K., Picker, L. J., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0606661103 · Cited by 225 · see citing works
Rochon, J., Bales, C. W., Ravussin, É., Redman, L. M., Holloszy, J. O., Racette, S. B., Roberts, S. B., Das, S. K., Romashkan, S., Galan, K. M., et al. (2010) · The Journals of Gerontology Series A · doi:10.1093/gerona/glq168 · Cited by 203 · see citing works
Self-citationYang, H., Youm, Y.-H., & Dixit, V. D. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0900562 · Cited by 196 · see citing works
Self-citationThe CALERIE Study: Design and methods of an innovative 25% caloric restriction intervention
Rickman, A. D., Williamson, D. A., Martin, C. K., Gilhooly, C. H., Stein, R. I., Bales, C. W., Roberts, S., & Das, S. K. (2011) · Contemporary Clinical Trials · doi:10.1016/j.cct.2011.07.002 · Cited by 163 · see citing works
Self-citationSerum concentrations of TNF-α and soluble TNF-α receptors in obesity
Zahorska‐Markiewicz, B., Janowska, J., Olszanecka‐Glinianowicz, M., & Żurakowski, A. (2000) · International Journal of Obesity · doi:10.1038/sj.ijo.0801398 · Cited by 149 · see citing works
Caloric Restriction Decreases Survival of Aged Mice in Response to Primary Influenza Infection
Gardner, E. M. (2005) · The Journals of Gerontology Series A · doi:10.1093/gerona/60.6.688 · Cited by 141 · see citing works
Analysis of Longitudinal Data,
Walters, S. J. (2003) · Journal of the Royal Statistical Society Series D (The Statistician) · doi:10.1046/j.1467-9884.2003.t01-4-00383_6.x · Cited by 137 · see citing works
Sun, D.-X., Muthukumar, A., Lawrence, R., & Fernandes, G. (2001) · Clinical Diagnostic Laboratory Immunology · doi:10.1128/cdli.8.5.1003-1011.2001 · Cited by 123 · see citing works
Association Between Circulating White Blood Cell Count and Cancer Mortality
Shankar, A., Wang, J. J., Rochtchina, E., Yu, M. C., Kefford, R. F., & Mitchell, P. (2006) · Archives of Internal Medicine · doi:10.1001/archinte.166.2.188 · Cited by 111 · see citing works
Relationship between white blood cell count and incident hypertension
Shankar, A. (2004) · American Journal of Hypertension · doi:10.1016/j.amjhyper.2003.11.005 · Cited by 108 · see citing works
Goldberg, E. L., Romero-Aleshire, M. J., Renkema, K. R., Ventevogel, M. S., Chew, W. M., Uhrlaub, J. L., Smithey, M. J., Limesand, K. H., Sempowski, G. D., Brooks, H. L., et al. (2014) · Aging Cell · doi:10.1111/acel.12280 · Cited by 102 · see citing works
Ritz, B. W., Aktan, I., Nogusa, S., & Gardner, E. M. (2008) · Journal of Nutrition · doi:10.3945/jn.108.093633 · Cited by 92 · see citing works
Toriola, A. T., Cheng, T. D., Neuhouser, M. L., Wener, M. H., Zheng, Y., Brown, E. C., Miller, J. W., Song, X., Beresford, S. A. A., Gunter, M. J., et al. (2012) · International Journal of Cancer · doi:10.1002/ijc.27942 · Cited by 86 · see citing works
Stewart, T. M., Bhapkar, M. V., Das, S. K., Galan, K. M., Martin, C. K., McAdams, L. H., Pieper, C. F., Redman, L. M., Roberts, S. B., Stein, R. I., et al. (2012) · Contemporary Clinical Trials · doi:10.1016/j.cct.2012.08.011 · Cited by 81 · see citing works
Self-citationWhite Blood Cell Count and Risk of Incident Atrial Fibrillation (From the Framingham Heart Study)
Rienstra, M., Sun, F. X., Magnani, J. W., Sinner, M. F., Lubitz, S. A., SULLIVAN, L. M., Ellinor, P. T., & Benjamin, E. J. (2011) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2011.09.049 · Cited by 81 · see citing works
Fontana, L. (2009) · Experimental Gerontology · doi:10.1016/j.exger.2008.04.005 · Cited by 81 · see citing works
Self-citationKristan, D. M. (2007) · Aging Cell · doi:10.1111/j.1474-9726.2007.00345.x · Cited by 77 · see citing works
Calorie Restriction Enhances T-Cell-Mediated Immune Response in Adult Overweight Men and Women
Ahmed, T., Das, S. K., Golden, J. K., Saltzman, E. J., Roberts, S. B., & Meydani, S. N. (2009) · The Journals of Gerontology Series A · doi:10.1093/gerona/glp101 · Cited by 73 · see citing works
Self-citationC-Reactive Protein and Cardiovascular Diseases—Is it Ready for Primetime?
Lavie, C. J., Milani, R. V., Verma, A., & O’Keefe, J. H. (2009) · The American Journal of the Medical Sciences · doi:10.1097/maj.0b013e3181c61b66 · Cited by 72 · see citing works
Lorenzo, C., Hanley, A. J., & Haffner, S. M. (2013) · Diabetologia · doi:10.1007/s00125-013-3080-0 · Cited by 71 · see citing works
Chae, J. S., Paik, J. K., Kang, R., Kim, M., Choi, Y., Lee, S., & Lee, J. H. (2013) · Nutrition Research · doi:10.1016/j.nutres.2013.01.005 · Cited by 64 · see citing works
Reduced Immune Responses in Rhesus Monkeys Subjected to Dietary Restriction
Roecker, E. B., Kemnitz, J. W., Ershler, W. B., & Weindruch, R. H. (1996) · The Journals of Gerontology Series A · doi:10.1093/gerona/51a.4.b276 · Cited by 49 · see citing works
Development of adherence metrics for caloric restriction interventions
Pieper, C. F., Redman, L. M., Racette, S. B., Roberts, S. B., Bhapkar, M. V., Rochon, J., Martin, C. K., Kraus, W. E., Das, S. K., Williamson, D., et al. (2011) · Clinical Trials · doi:10.1177/1740774511398369 · Cited by 49 · see citing works
Self-citationClinthorne, J. F., Adams, D. J., Fenton, J. I., Ritz, B. W., & Gardner, E. M. (2010) · Journal of Nutrition · doi:10.3945/jn.110.122408 · Cited by 38 · see citing works
Formoso, G., Taraborrelli, M., Guagnano, M. T., D’Adamo, M., Pietro, N. D., Tartaro, A., & Consoli, A. (2012) · PLoS ONE · doi:10.1371/journal.pone.0052774 · Cited by 22 · see citing works
Relationship between white blood cell count and incident hypertension
WHITWORTH, J. (2004) · American Journal of Hypertension · doi:10.1016/j.amjhyper.2004.05.021 · Cited by 11 · see citing works
Nikolich‐Žugich, J. (2015) · ImmPort · doi:10.21430/m33e7tcyxt · Cited by 1 · see citing works
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Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty
Ferrucci, L., & Fabbri, E. (2018) · Nature Reviews Cardiology · doi:10.1038/s41569-018-0064-2 · Cited by 3,690 · see citing works
Franceschi, C., Garagnani, P., Vitale, G., Capri, M., & Salvioli, S. (2017) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2016.09.005 · Cited by 997 · see citing works
Aging and age‐related diseases: from mechanisms to therapeutic strategies
Li, Z., Zhang, Z., Ren, Y., Wang, Y., Fang, J., Yue, H., Ma, S., & Guan, F. (2021) · Biogerontology · doi:10.1007/s10522-021-09910-5 · Cited by 668 · see citing works
Intermittent Fasting Confers Protection in CNS Autoimmunity by Altering the Gut Microbiota
Cignarella, F., Cantoni, C., Ghezzi, L., Salter, A., Dorsett, Y., Chen, L., Phillips, D., Weinstock, G. M., Fontana, L., Cross, A. H., et al. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.05.006 · Cited by 568 · see citing works
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Nelke, C., Dziewas, R., Minnerup, J., Meuth, S. G., & Ruck, T. (2019) · eBioMedicine · doi:10.1016/j.ebiom.2019.10.034 · Cited by 437 · see citing works
Stekovic, S., Hofer, S. J., Tripolt, N., Aon, M. A., Royer, P., Pein, L., Stadler, J. T., Pendl, T., Prietl, B., Url, J., et al. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.07.016 · Cited by 412 · see citing works
DNA damage and repair in age-related inflammation
Zhao, Y., Simon, M. A., Seluanov, A., & Gorbunova, V. A. (2022) · Nature reviews. Immunology · doi:10.1038/s41577-022-00751-y · Cited by 393 · see citing works
Inflamm-ageing: the role of inflammation in age-dependent cardiovascular disease
Liberale, L., Montecucco, F., Tardif, J., Libby, P., & Camici, G. G. (2020) · European Heart Journal · doi:10.1093/eurheartj/ehz961 · Cited by 347 · see citing works
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Spadaro, O., Youm, Y., Shchukina, I., Ryu, S., Sidorov, S., Ravussin, A., Nguyen, K., Aladyeva, E., Predeus, A. N., Smith, S. R., et al. (2022) · Science · doi:10.1126/science.abg7292 · Cited by 317 · see citing works
Self-citationInterconnections between Inflammageing and Immunosenescence during Ageing
Teissier, T., Boulanger, É., & Cox, L. S. (2022) · Cells · doi:10.3390/cells11030359 · Cited by 310 · see citing works
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Abdellatif, M., Rainer, P. P., Sedej, S., & Kroemer, G. (2023) · Nature Reviews Cardiology · doi:10.1038/s41569-023-00881-3 · Cited by 285 · see citing works
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Venter, C., Eyerich, S., Sarin, T., & Klatt, K. C. (2020) · Nutrients · doi:10.3390/nu12030818 · Cited by 247 · see citing works
Pan, F., Zhang, L., Li, M., Hu, Y., Zeng, B., Yuan, H., Zhao, L., & Zhang, C. (2018) · Microbiome · doi:10.1186/s40168-018-0440-5 · Cited by 236 · see citing works
Targeting immune dysfunction in aging
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Inflammaging and human longevity in the omics era
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Vitale, G., Pellegrino, G., Vollery, M., & Hofland, L. J. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00027 · Cited by 166 · see citing works
Dietary Restriction Extends Lifespan through Metabolic Regulation of Innate Immunity
Wu, Z., Isik, M., Moroz, N., Steinbaugh, M. J., Zhang, P., & Blackwell, T. K. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.02.013 · Cited by 160 · see citing works
Intermittent fasting in the prevention and treatment of cancer
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Delgado‐Morales, R., Agís‐Balboa, R. C., Esteller, M., & Berdasco, M. (2017) · Clinical Epigenetics · doi:10.1186/s13148-017-0365-z · Cited by 143 · see citing works
Neutrophils in aging and aging‐related pathologies
Avondt, K. V., Strecker, J., Tulotta, C., Minnerup, J., Schulz, C., & Soehnlein, O. (2022) · Immunological Reviews · doi:10.1111/imr.13153 · Cited by 146 · see citing works
Control of immunity via nutritional interventions
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Weight loss is a critical factor to reduce inflammation
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Nutrition and Athlete Immune Health: New Perspectives on an Old Paradigm
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Self-citationThe matricellular protein SPARC induces inflammatory interferon-response in macrophages during aging
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Self-citationEffects of dietary restriction on neuroinflammation in neurodegenerative diseases
Fontana, L., Ghezzi, L., Cross, A. H., & Piccio, L. M. (2020) · The Journal of Experimental Medicine · doi:10.1084/jem.20190086 · Cited by 116 · see citing works
Self-citationSkin immunity: dissecting the complex biology of our body's outer barrier
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Dorling, J. L., Martin, C. K., & Redman, L. M. (2020) · Ageing Research Reviews · doi:10.1016/j.arr.2020.101038 · Cited by 118 · see citing works
Nrf2/ARE Pathway Modulation by Dietary Energy Regulation in Neurological Disorders
Vasconcelos, A. R., dos Santos, N. B., Scavone, C., & Munhoz, C. D. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2019.00033 · Cited by 112 · see citing works
Caloric restriction and cellular senescence
Fontana, L., Nehme, J., & Demaria, M. (2018) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2018.10.005 · Cited by 104 · see citing works
Self-citationDonia, T., & Khamis, A. A. (2021) · Environmental Science and Pollution Research · doi:10.1007/s11356-021-14109-9 · Cited by 108 · see citing works
Dorling, J. L., van Vliet, S., Huffman, K. M., Kraus, W. E., Bhapkar, M. V., Pieper, C. F., Stewart, T. M., Das, S. K., Racette, S. B., Roberts, S. B., et al. (2020) · Nutrition Reviews · doi:10.1093/nutrit/nuaa085 · Cited by 99 · see citing works
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Zhang, L., Liu, Z., Wang, J., Li, R., Ren, J.-Y., Gao, X., Lv, S., Liang, L., Zhang, F., Yin, B., et al. (2022) · iScience · doi:10.1016/j.isci.2022.104870 · Cited by 97 · see citing works
Schmitt, C. C., Aranias, T., Viel, T., Château, D., Gall, M. L., Waligora‐Dupriet, A., Melchior, C., Rouxel, O., Kapel, N., Gourcerol, G., et al. (2016) · Molecular Metabolism · doi:10.1016/j.molmet.2016.10.008 · Cited by 91 · see citing works
Mihaylova, 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
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Self-citationRomeo, S., Vidal‐Puig, A., Husain, M., Ahima, R. S., Arca, M., Bhatt, D. L., Diehl, A. M., Fontana, L., Foo, R., Frühbeck, G., et al. (2025) · European Heart Journal · doi:10.1093/eurheartj/ehaf314 · Cited by 91 · see citing works
Self-citationFontana, L., Mitchell, S. E., Wang, B., Tosti, V., van Vliet, T., Veronese, N., Bertozzi, B., Early, D. S., Maissan, P., Speakman, J. R., et al. (2018) · Aging Cell · doi:10.1111/acel.12746 · Cited by 81 · see citing works
“These data suggest that CR could potentially prevent the accumulation of age-associated senescent cells in the colon mucosa of human beings, and the reduction in senescence might explain the much lower levels of inflammation observed in CR individuals (Meydani et al., 2016).”
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Franceschi, C., Ostan, R., & Santoro, A. (2018) · Annual Review of Nutrition · doi:10.1146/annurev-nutr-082117-051637 · Cited by 81 · see citing works
Healthy ageing: the natural consequences of good nutrition—a conference report
Marsman, D. S., Belsky, D. W., Gregori, D., Johnson, M. A., Dog, T. L., Meydani, S. N., Pigat, S., Sadana, R., Shao, A., & Griffiths, J. C. (2018) · European Journal of Nutrition · doi:10.1007/s00394-018-1723-0 · Cited by 81 · see citing works
Self-citationField, R., Pourkazemi, F., Turton, J. L., & Rooney, K. B. (2020) · Pain Medicine · doi:10.1093/pm/pnaa378 · Cited by 73 · see citing works
Rasa, S. M. M., Annunziata, F., Křepelová, A., Nunna, S., Omrani, O., Gebert, N., Adam, L., Käppel, S., Hoehn, S., Donati, G., et al. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.111017 · Cited by 69 · see citing works
Anti-Inflammatory Diets in Fertility: An Evidence Review
Alesi, S., Villani, A. M., Mantzioris, E., Takele, W. W., Cowan, S., Moran, L., & Mousa, A. (2022) · Nutrients · doi:10.3390/nu14193914 · Cited by 75 · 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
Fasting-induced FOXO4 blunts human CD4+ T helper cell responsiveness
Han, K., Singh, K., Rodman, M. J., Hassanzadeh, S., Wu, K., Nguyen, A., Huffstutler, R. D., Seifuddin, F., Dagur, P. K., Saxena, A., et al. (2021) · Nature Metabolism · doi:10.1038/s42255-021-00356-0 · Cited by 69 · see citing works
Does Relative Energy Deficiency in Sport (REDs) Syndrome Exist?
Jeukendrup, A. E., Areta, J. L., Genechten, L. V., Langan‐Evans, C., Pedlar, C. R., Rodas, G., Sale, C., & Walsh, N. P. (2024) · Sports Medicine · doi:10.1007/s40279-024-02108-y · Cited by 75 · see citing works
Hebebrand, J., Hildebrandt, T., Schlögl, H., Seitz, J., Denecke, S., Vieira, D. B., Gradl-Dietsch, G., Peters, T., Antel, J., Lau, D., et al. (2022) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2022.104807 · Cited by 61 · see citing works
The sedentary (r)evolution: Have we lost our metabolic flexibility?
Freese, J., Klement, R. J., Ruiz-Núñez, B., Schwarz, S., & Lötzerich, H. (2017) · F1000Research · doi:10.12688/f1000research.12724.2 · Cited by 74 · see citing works
Training vs. Tolerance: The Yin/Yang of the Innate Immune System
Lajqi, T., Köstlin‐Gille, N., Bauer, R., Zarogiannis, S. G., Lajqi, E., Ajeti, V., Dietz, S., Kranig, S. A., Rühle, J., Demaj, A., et al. (2023) · Biomedicines · doi:10.3390/biomedicines11030766 · Cited by 57 · see citing works
Wilson, K. A., Chamoli, M., Hilsabeck, T. A. U., Pandey, M., Bansal, S., Chawla, G., & Kapahi, P. (2021) · Cell Metabolism · doi:10.1016/j.cmet.2021.08.018 · Cited by 56 · see citing works
Plasma cells: You are what you eat
D’Souza, L. J., & Bhattacharya, D. (2019) · Immunological Reviews · doi:10.1111/imr.12732 · Cited by 54 · see citing works
The immune remodel: Weight loss-mediated inflammatory changes to obesity
Phillips, C. L., & Grayson, B. E. (2020) · Experimental Biology and Medicine · doi:10.1177/1535370219900185 · Cited by 56 · see citing works
Calorie restriction protects neural stem cells from age-related deficits in the subventricular zone
Apple, D. M., Mahesula, S., Fonseca, R. S., Zhu, C., & Kokovay, E. (2019) · Aging · doi:10.18632/aging.101731 · Cited by 54 · see citing works
Contreras, N. A., Fontana, L., Tosti, V., & Nikolich‐Žugich, J. (2018) · GeroScience · doi:10.1007/s11357-018-0022-2 · Cited by 53 · see citing works
Self-citationAnti-Aging Effects of Calorie Restriction (CR) and CR Mimetics Based on the Senoinflammation Concept
Kim, D. H., Bang, E., Jung, H. J., Noh, S. G., Yu, B. P., Choi, Y. J., & Chung, H. Y. (2020) · Nutrients · doi:10.3390/nu12020422 · Cited by 53 · see citing works
Laurens, C., Grundler, F., Damiot, A., Chery, I., LeMaho, A. L., Zahariev, A., Maho, Y. L., Bergouignan, A., Gauquelin-Koch, G., Simon, C., et al. (2021) · Journal of Cachexia, Sarcopenia and Muscle · doi:10.1002/jcsm.12766 · Cited by 46 · see citing works
Epigenetic Regulation of Metabolism and Inflammation by Calorie Restriction
Hernández‐Saavedra, D., Moody, L., Xu, G. B., Chen, H., & Pan, Y. (2018) · Advances in Nutrition · doi:10.1093/advances/nmy129 · Cited by 51 · see citing works
Attinà, A., Leggeri, C., Paroni, R., Pivari, F., Dei Cas, M., Mingione, A., Dri, M., Marchetti, M., & Di Renzo, L. (2021) · Nutrients · doi:10.3390/nu13051570 · Cited by 47 · see citing works
Genetic background, epigenetic factors and dietary interventions which influence human longevity
Costa, D., Scognamiglio, M., Fiorito, C., Benincasa, G., & Claudio Napoli, A. (2019) · Biogerontology · doi:10.1007/s10522-019-09824-3 · Cited by 45 · see citing works
Xie, Y., Gu, Y., Li, Z., He, B., & Zhang, L. (2024) · Nutrients · doi:10.3390/nu16173007 · Cited by 48 · see citing works
Piccirillo, F., Carpenito, M., Verolino, G., Chello, C., Nusca, A., Lusini, M., Spadaccio, C., Nappi, F., Sciascio, G. D., & Nenna, A. (2019) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2019.111161 · Cited by 42 · see citing works
Caristia, S., Vito, M. D., Sarro, A., Leone, A., Pecere, A., Zibetti, A., Filigheddu, N., Zeppegno, P., Prodam, F., Faggiano, F., et al. (2020) · Nutrients · doi:10.3390/nu12082290 · Cited by 42 · see citing works
A systems-approach to NAD+ restoration
Conlon, N. J., & Ford, D. (2022) · Biochemical Pharmacology · doi:10.1016/j.bcp.2022.114946 · Cited by 40 · see citing works
Mthembu, S. X. H., Mazibuko-Mbeje, S. E., Ziqubu, K., Nyawo, T. A., Obonye, N., Nyambuya, T. M., Nkambule, B. B., Silvestri, S., Tiano, L., Muller, C. J. F., et al. (2022) · Life Sciences · doi:10.1016/j.lfs.2022.120467 · Cited by 40 · see citing works
Zhang, L., Xue, X., Zhai, R., Yang, X., Li, H., Zhao, L., & Zhang, C. (2019) · mSystems · doi:10.1128/msystems.00348-19 · Cited by 40 · see citing works
De Souza, M. J., Strock, N. C. A., Ricker, E. A., Koltun, K. J., Barrack, M., Joy, E., Nattiv, A., Hutchinson, M., Misra, M., & Williams, N. I. (2022) · Sports Medicine · doi:10.1007/s40279-021-01568-w · Cited by 39 · see citing works
Physiological Systems in Promoting Frailty
Perazza, L. R., Brown‐Borg, H. M., & Thompson, L. V. (2022) · Comprehensive physiology · doi:10.1002/cphy.c210034 · Cited by 64 · see citing works
The role of dietary strategies in the modulation of hallmarks of aging
de França, N. A. G., Rolland, Y., Guyonnet, S., & Barreto, P. D. S. (2023) · Ageing Research Reviews · doi:10.1016/j.arr.2023.101908 · Cited by 38 · see citing works
Hastings, W. J., Ye, Q., Wolf, S. E., Ryan, C. P., Das, S. K., Huffman, K. M., Kobor, M. S., Kraus, W. E., MacIsaac, J. L., Martin, C. K., et al. (2024) · Aging Cell · doi:10.1111/acel.14149 · Cited by 36 · see citing works
Self-citationAgeing, cellular senescence and the impact of diet: an overview
Maduro, A. I., Luís, C., & Soares, R. A. (2021) · Porto Biomedical Journal · doi:10.1097/j.pbj.0000000000000120 · Cited by 36 · see citing works
Obesity accelerates age defects in B cells, and weight loss improves B cell function
Frasca, D., Romero, M., Diaz, A., & Blomberg, B. B. (2023) · Immunity & Ageing · doi:10.1186/s12979-023-00361-9 · Cited by 36 · see citing works
Reduction of SPARC protects mice against NLRP3 inflammasome activation and obesity
Ryu, S., Spadaro, O., Sidorov, S., Lee, A. H., Caprio, S., Morrison, C. D., Smith, S. R., Ravussin, É., Shchukina, I., Artyomov, M. N., et al. (2023) · Journal of Clinical Investigation · doi:10.1172/jci169173 · Cited by 34 · see citing works
Self-citationKebbe, M., Sparks, J. R., Flanagan, E. W., & Redman, L. M. (2021) · Expert Review of Endocrinology & Metabolism · doi:10.1080/17446651.2021.1922077 · Cited by 39 · see citing works
Feriel, J., Tchipeva, D., & Depasse, F. (2021) · International Journal of Laboratory Hematology · doi:10.1111/ijlh.13590 · Cited by 33 · see citing works
Nutrition and dietary restrictions in cancer prevention
Mishra, A. K., Giuliani, G., & Longo, V. D. (2023) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2023.189063 · Cited by 37 · see citing works
Dorling, J. L., Ravussin, É., Redman, L. M., Bhapkar, M. V., Huffman, K. M., Racette, S. B., Das, S. K., Apolzan, J. W., Kraus, W. E., Höchsmann, C., et al. (2020) · European Journal of Nutrition · doi:10.1007/s00394-020-02361-7 · Cited by 32 · see citing works
Self-citationEriau, E., Paillet, J., Kroemer, G., & Pol, J. G. (2021) · Cancers · doi:10.3390/cancers13061260 · Cited by 31 · see citing works
Hernández-Calderón, P., Wiedemann, L., & Benítez‐Páez, A. (2022) · Frontiers in Nutrition · doi:10.3389/fnut.2022.1006747 · Cited by 32 · see citing works
Effects of dietary restriction on gut microbiota and CNS autoimmunity
Cantoni, C., Dorsett, Y., Fontana, L., Zhou, Y., & Piccio, L. M. (2020) · Clinical Immunology · doi:10.1016/j.clim.2020.108575 · Cited by 31 · see citing works
Self-citationHan, K., Meadows, A. M., Rodman, M. J., Russo, A. C., Sharma, R., Singh, K., Hassanzadeh, S., Dagur, P. K., Huffstutler, R. D., Krause, F. N., et al. (2024) · Journal of Leukocyte Biology · doi:10.1093/jleuko/qiae006 · Cited by 31 · see citing works
Physiological Systems in Promoting Frailty
Perazza, L. R., Brown‐Borg, H. M., & Thompson, L. V. (2022) · Comprehensive physiology · doi:10.1002/j.2040-4603.2022.tb00224.x · Cited by 30 · see citing works
Khan, A. H., Chowers, I., & Lotery, A. J. (2023) · Cells · doi:10.3390/cells12131708 · Cited by 31 · see citing works
Wang, L., Cheng, M., Wang, Y.-C., Chen, J. W., Xie, F., Huang, L.-H., & Zhan, C. (2024) · Nature Neuroscience · doi:10.1038/s41593-023-01543-w · Cited by 28 · see citing works
Yegla, B., & Foster, T. C. (2019) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2019.00296 · Cited by 28 · see citing works
Sbierski‐Kind, J., Mai, K., Kath, J., Jurisch, A., Streitz, M., Kuchenbecker, L., Babel, N., Nienen, M., Jürchott, K., Spranger, L., et al. (2020) · The Journal of Immunology · doi:10.4049/jimmunol.2000108 · Cited by 27 · see citing works
Tang, Z., Ming, Y., Wu, M., Jing, J., Xu, S., Li, H., & Zhu, Y. (2021) · Nutrients · doi:10.3390/nu13093222 · Cited by 27 · see citing works
Intermittent Fasting: Myths, Fakes and Truth on This Dietary Regimen Approach
Brogi, S., Tabanelli, R., Puca, S., & Calderone, V. (2024) · Foods · doi:10.3390/foods13131960 · Cited by 26 · see citing works
Nutrigenetics and nutrigenomics—A personalized approach to nutrition
Ahluwalia, M. K. (2021) · Advances in genetics · doi:10.1016/bs.adgen.2021.08.005 · Cited by 26 · see citing works
Glucose metabolism and glycosylation link the gut microbiota to autoimmune diseases
Wang, L., Xu, H., Yang, H., Zhou, J., Zhao, L., & Zhang, F. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.952398 · Cited by 26 · see citing works
Intermittent Fasting: Myths, Fakes and Truth on this Dietary Regimen Approach
Brogi, S., Tabanelli, R., Puca, S., & Calderone, V. (2024) · doi:10.20944/preprints202405.1820.v1 · Cited by 26 · see citing works
Function and treatment strategies of β-hydroxybutyrate in aging
Xiang, Y., Wang, Q., Lan, X., Zhang, H., & Wei, D. (2022) · Smart Materials in Medicine · doi:10.1016/j.smaim.2022.09.003 · Cited by 25 · see citing works
Benjamin, C., & Crews, R. (2024) · Metabolites · doi:10.3390/metabo14060341 · Cited by 23 · see citing works
Tomiyama, A. J., Milush, J. M., Lin, J., Flynn, J. M., Kapahi, P., Verdin, E. M., Sinclair, E., Melov, S., & Epel, E. S. (2017) · Nutrition and Healthy Aging · doi:10.3233/nha-160017 · Cited by 24 · see citing works
Dietary Regulation of Memory T Cells
Collins, N. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21124363 · Cited by 24 · see citing works
Metabolic regulation of immunological aging
Kim, H., & Dixit, V. D. (2025) · Nature Aging · doi:10.1038/s43587-025-00921-2 · Cited by 30 · see citing works
Self-citationRibosomal DNA instability: An evolutionary conserved fuel for inflammaging
Storci, G., Bacalini, M. G., Bonifazi, F., Garagnani, P., Carolis, S. D., Salvioli, S., Olivieri, F., & Bonafè, M. (2020) · Ageing Research Reviews · doi:10.1016/j.arr.2020.101018 · Cited by 23 · see citing works
- Authors
- Meydani, S. N., Das, S. K., Pieper, C. F., Lewis, M. R., Klein, S., Dixit, V. D., Gupta, A. K., Villareal, D. T., Bhapkar, M., Huang, M., Fuss, P. J., Roberts, S. B., Holloszy, J. O., & Fontana, L.
- Affiliations
- Tufts University (US)
- Duke Medical Center (US)
- University of Vermont (US)
- Washington University in St. Louis (US)
- Yale University (US)
- Pennington Biomedical Research Center (US)
- Michael E. DeBakey VA Medical Center (US)
- Corresponding author
- Meydani, Simin N.
- ORCID
- Venue
- Aging
- Publisher
- Impact Journals, LLC
- Published
- 2016-07-13
- Volume
- 8
- Issue
- 7
- Pages
- 1416-1431
- ISSN
- 1945-4589 (ISSN-L)
- PMC
- PMC4993339
- OpenAlex
- W2470302757
- Cited by
- 228
- References
- 53
- Citations by year
- 2026: 18 · 2025: 23 · 2024: 25 · 2023: 28 · 2022: 38 · 2021: 29 · 2020: 22 · 2019: 21 · 2018: 17 · 2017: 4 · 2016: 3
- FWCI
- 12.07
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- Aging (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Digital Commons@Becker (Washington University School of Medicine) (submittedVersion)
- Institutional Research Information System (Università degli Studi di Brescia) (submittedVersion)
- Funders
- U.S. Department of Agriculture (#58–1950-0-014)
- National Institutes of Health
- National Institute on Aging (U01AG020478, U01AG020487, U01AG020480, U01AG022132)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK056341)
- Topics
- Health Sciences › Medicine › Physiology › Dietary Effects on Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Rehabilitation › Exercise and Physiological Responses
- Keywords
- caloric restriction, inflammation, cell-mediated immunity, non-obese adults, C-reactive protein, TNF-α, ICAM-1, leptin, lymphocyte count, delayed-type hypersensitivity, vaccine antibody response, weight loss
- MeSH terms
- Adult, Body Composition, C-Reactive Protein, Energy Intake, Diet, Female, Humans, Inflammation, Male, Middle Aged, Tumor Necrosis Factor-alpha, Biomarkers, Treatment Outcome, Lymphocyte Count, Intercellular Adhesion Molecule-1, Leptin, Caloric Restriction
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