Aging is associated with circulating cytokine dysregulation
Abstract
Purpose Aging is accompanied by a progressive increase in pro-inflammatory cytokine status. However, little is known about the development of age-dependent modifications in other circulating cytokines. The aim of this study was to investigate in vivo the influence of age on circulating cytokine production in healthy subjects (HC).Methods Circulating cytokines were measured by CBA and ELISA in 73 HC. Intracellular cytokine production was assessed in CD3+ and CD14+ cells by flow cytometry. Production of cytokines in cell culture supernatants was also studied after polyclonal stimulation.Results Subjects were divided into three different groups according to age: 28 young HC (<30 years, 26.2 ± 2.4), 24 middle age HC (30-60 years, 44.7 ± 8.4) and 21 elderly HC (>60 years, 70.6 ± 7.9). Age was positively correlated with the circulating levels of IL-12p70, IL-1β, TNFα, IL-6, and IL-10. Age had a negative correlation with circulating levels of IL-17. Besides, age was positively correlated with spontaneous intracellular expression of proinflammatory cytokines in circulating monocytes. No correlation was found with other intracellular cytokine expression or with the production of cytokines in cell culture supernatants after in vitro stimulation. Gender had a marginal effect on the circulating cytokine profile.Conclusion Aging has a significant impact on the production of circulating cytokines in healthy individuals. The circulating cytokine milieu may contribute to the development of age-restricted conditions.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Inflammageing involves higher circulating levels of inflammatory mediators such as CRP, IL-6, and TNFα.
“Inflammageing is characterised by an increase in circulating inflammatory mediators such as C Reactive protein (CRP), Interleukin (IL)-6 and Tumour Necrosis Factor (TNF)α (18).”
From The impact of ageing on monocytes and macrophages (2021) · cites this paper as [18]
Cites
(1990) · Choice Reviews Online · doi:10.5860/choice.27-3338 · Cited by 35,305 · see citing works
Hosmer, D. W., & Lemeshow, S. (2000) · doi:10.1002/0471722146 · Cited by 20,302 · see citing works
A note on a general definition of the coefficient of determination
NAGELKERKE, N. J. D. (1991) · Biometrika · doi:10.1093/biomet/78.3.691 · Cited by 5,927 · see citing works
Applied Logistic Regression Analysis
Ziegel, E. R., & Menard, S. (1996) · Technometrics · doi:10.1080/00401706.1996.10484485 · Cited by 3,923 · see citing works
Aldenderfer, M. S., & Blashfield, R. K. (1984) · Cited by 2,358 · see citing works
Franceschi, C., Capri, M., Monti, D., Giunta, S., Olivieri, F., Sevini, F., Panourgia, M. P., Invidia, L., Celani, L., Scurti, M., et al. (2007) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2006.11.016 · Cited by 2,087 · see citing works
IL-17 family cytokines and the expanding diversity of effector T cell lineages
Weaver, C. T., Hatton, R. D., Mangan, P. R., & Harrington, L. E. (2007) · Annual Review of Immunology · doi:10.1146/annurev.immunol.25.022106.141557 · Cited by 1,842 · see citing works
Age-Associated Increased Interleukin-6 Gene Expression, Late-Life Diseases, and Frailty
Ershler, W. B., & Keller, E. T. (2000) · Annual Review of Medicine · doi:10.1146/annurev.med.51.1.245 · Cited by 1,282 · see citing works
The origins of age-related proinflammatory state
Ferrucci, L., Corsi, A., Lauretani, F., Bandinelli, S., Bartali, B., Taub, D. D., Guralnik, J. M., & Longo, D. L. (2005) · Blood · doi:10.1182/blood-2004-07-2599 · Cited by 908 · see citing works
Posnett, D. N., Sinha, R., Kabak, S., & Russo, C. (1994) · The Journal of Experimental Medicine · doi:10.1084/jem.179.2.609 · Cited by 761 · see citing works
Increased cytokine production in mononuclear cells of healthy elderly people
Fagiolo, U., Cossarizza, A., Scala, E., Fanales‐Belasio, E., Ortolani, C., Cozzi, E., Monti, D., Franceschi, C., & Paganelli, R. (1993) · European Journal of Immunology · doi:10.1002/eji.1830230950 · Cited by 665 · see citing works
Plackett, T. P., Boehmer, E. D., Faunce, D. E., & Kovacs, E. J. (2004) · Journal of Leukocyte Biology · doi:10.1189/jlb.1103592 · Cited by 351 · see citing works
Cellular sources and immune functions of interleukin-9
Noelle, R. J., & Nowak, E. C. (2010) · Nature reviews. Immunology · doi:10.1038/nri2848 · Cited by 301 · see citing works
Wikby, A., Nilsson, B.-O., Forsey, R. J., Thompson, J., Strindhall, J., Löfgren, S., Ernerudh, J., Pawelec, G., Ferguson, F. G., & Johansson, B. E. A. (2006) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2006.04.003 · Cited by 284 · see citing works
Plasma cytokine profiles in elderly humans
Forsey, R. J., Thompson, J. M., Ernerudh, J., HURST, T. L., Strindhall, J., Johansson, B. E. A., Nilsson, B.-O., & Wikby, A. (2003) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(03)00025-3 · Cited by 249 · see citing works
WALDENSTRÖM, J. G. (1984) · Acta Medica Scandinavica · doi:10.1111/j.0954-6820.1984.tb05032.x · Cited by 248 · see citing works
Effects of aging on T cell function
Haynes, L., & Maue, A. C. (2009) · Current Opinion in Immunology · doi:10.1016/j.coi.2009.05.009 · Cited by 244 · see citing works
Aging, Longevity, Inflammation, and Cancer
Caruso, C., Lio, D., Cavallone, L., & Franceschi, C. (2004) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1322.001 · Cited by 219 · see citing works
Influence of Physical Activity on Serum IL-6 and IL-10 Levels in Healthy Older Men
Jankord, R., & Jemioło, B. (2004) · Medicine & Science in Sports & Exercise · doi:10.1249/01.mss.0000128186.09416.18 · Cited by 196 · see citing works
Heterogeneity of human effector CD4+ T cells
Annunziato, F., & Romagnani, S. (2009) · Arthritis Research & Therapy · doi:10.1186/ar2843 · Cited by 194 · see citing works
(1997) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(96)01849-0 · Cited by 174 · see citing works
O’Mahony, L., Holland, J., Jackson, J., Feighery, C., Hennessy, T. P. J., & Mealy, K. (1998) · Clinical & Experimental Immunology · doi:10.1046/j.1365-2249.1998.00641.x · Cited by 173 · see citing works
Interleukin-6 Production Does Not Increase With Age
Beharka, A. A., Meydani, M., Wu, D., Leka, L. S., Meydani, A., & Meydani, S. N. (2001) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/56.2.b81 · Cited by 169 · see citing works
Giuliani, N., Sansoni, P., Girasole, G., Vescovini, R., Passeri, G., Passeri, M., & Pedrazzoni, M. (2001) · Experimental Gerontology · doi:10.1016/s0531-5565(00)00220-5 · Cited by 151 · see citing works
Cytokine production pathway in the elderly
Caruso, C., Candore, G., Cigna, D., Lorenzo, G. D., Sireci, G., Dieli, F., & Salerno, A. (1996) · Immunologic Research · doi:10.1007/bf02918286 · Cited by 137 · see citing works
Alberti, S., Cevenini, E., Ostan, R., Capri, M., Salvioli, S., Bucci, L., Ginaldi, L., Martinis, M. D., Franceschi, C., & Monti, D. (2006) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2006.01.014 · Cited by 128 · see citing works
Davila, D. R., Edwards, C. K., Arkins, S., Simon, J., & Kelley, K. W. (1990) · The FASEB Journal · doi:10.1096/fasebj.4.11.2165948 · Cited by 123 · see citing works
Altered Th1/Th2 commitment in human CD4+ T cells with ageing
Sakata-Kaneko, S., Wakatsuki, Y., Matsunaga, Y., Usui, T., & Kita, T. (2000) · Clinical & Experimental Immunology · doi:10.1046/j.1365-2249.2000.01224.x · Cited by 121 · see citing works
Rea, I. M., Stewart, M., Campbell, P., et al. (2009) · Gerontology · doi:10.1159/000213775 · Cited by 112 · see citing works
Pietschmann, P., Gollob, E., Brosch, S., Hahn, P., Kudlacek, S. T., Willheim, M., Woloszczuk, W., Peterlik, M., & Tragl, K. H. (2003) · Experimental Gerontology · doi:10.1016/s0531-5565(03)00189-x · Cited by 109 · see citing works
Gender specificity of altered human immune cytokine profiles in aging
Goetzl, E. J., Huang, M., Kon, J., Patel, K. G., Schwartz, J. B., Fast, K., Ferrucci, L., Madara, K., Taub, D. D., & Longo, D. L. (2010) · The FASEB Journal · doi:10.1096/fj.10-160911 · Cited by 109 · see citing works
TH1 and TH2 cell polarization increases with aging and is modulated by zinc supplementation
Uciechowski, P., Kahmann, L., Plümäkers, B., Malavolta, M., Mocchegiani, E., Dedoussis, G., Herbein, G., Jajte, J., Fulop, T., & Rink, L. (2008) · Experimental Gerontology · doi:10.1016/j.exger.2007.11.006 · Cited by 97 · see citing works
Age-Related Differences in Cytokine Secretion
Riancho, J. A., Zarrabeitia, M. T., Amado, J. A., Olmos, J. M., & González-Macı́as, J. (2009) · Gerontology · doi:10.1159/000213568 · Cited by 88 · see citing works
Age-associated alteration in naive and memory Th17 cell response in humans
Lee, J. S., Lee, W., Kim, S., Kang, Y., Lee, N., Shin, M. S., Kang, S. W., & Kang, I. (2011) · Clinical Immunology · doi:10.1016/j.clim.2011.03.018 · Cited by 83 · see citing works
Chipeta, J., Komada, Y., Zhang, X., Deguchi, T., Sugiyama, K., Azuma, E., & Sakurai, M. (1998) · Cellular Immunology · doi:10.1006/cimm.1998.1244 · Cited by 76 · see citing works
Nuclear factor‐κB‐dependent reversal of aging‐induced alterations in T cell cytokines
Huang, M., Liao, J., Bonasera, S. J., Longo, D. L., & Goetzl, E. J. (2008) · The FASEB Journal · doi:10.1096/fj.07-103721 · Cited by 68 · see citing works
Karanfilov, C. I., Beiqing, L., Fox, C. C., Lakshmanan, R. R., & Whisler, R. L. (1999) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(99)00030-5 · Cited by 57 · see citing works
Rich, E. A., Mincek, M., Armitage, K. B., Duffy, E. G., Owen, D. C., Fayen, J. D., Hom, D. L., & Ellner, J. J. (2009) · Gerontology · doi:10.1159/000213519 · Cited by 50 · see citing works
Fietta, A. M., Merlini, C., Santos, C. D., et al. (2009) · Gerontology · doi:10.1159/000213591 · Cited by 47 · see citing works
Rodriguez, L. A., López‐Hoyos, M., Mata, C., Fontalba, A., Alén, J. C., Marín, M. J. A., Fernández-Luna, J. L., Balbín, J. A., Aranzamendi, M., Blanco, R., et al. (2011) · Annals of the Rheumatic Diseases · doi:10.1136/ard.2010.140194 · Cited by 37 · see citing works
Self-citationMartínez-Taboada, V. M., Bartolomé, M. J., Amado, J., Blanco, R., García‐Unzueta, M. T., Rodrı́guez-Valverde, V., & López‐Hoyos, M. (2002) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(02)00116-1 · Cited by 29 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Pinti, M., Cevenini, E., Nasi, M., De Biasi, S., Salvioli, S., Monti, D., Benatti, S., Gibellini, L., Cotichini, R., Stazi, M. A., et al. (2014) · European Journal of Immunology · doi:10.1002/eji.201343921 · Cited by 409 · see citing works
The impact of ageing on monocytes and macrophages
De Maeyer, R. P. H., & Chambers, E. S. (2021) · Immunology Letters · doi:10.1016/j.imlet.2020.12.003 · Cited by 275 · see citing works
Metcalf, T. U., Cubas, R. A., Ghneim, K., Cartwright, M. J., Grevenynghe, J. V., Richner, J. M., Olagnier, D. P., Wilkinson, P. A., Cameron, M. J., Park, B. S., et al. (2015) · Aging Cell · doi:10.1111/acel.12320 · Cited by 189 · see citing works
Sarcopenic obesity and endocrinal adaptation with age
Sakuma, K., & Yamaguchi, A. (2013) · International Journal of Endocrinology · doi:10.1155/2013/204164 · Cited by 189 · see citing works
Inflammation and age-associated skeletal muscle deterioration (sarcopaenia)
Wang, J., Leung, K.-S., Chow, S. K.-H., & Cheung, W.-H. (2017) · Journal of Orthopaedic Translation · doi:10.1016/j.jot.2017.05.006 · Cited by 173 · see citing works
Targeting macrophages rescues age‐related immune deficiencies in C57<scp>BL</scp>/6J geriatric mice
Jackaman, C., Radley‐Crabb, H. G., Soffe, Z., Shavlakadze, T., Grounds, M. D., & Nelson, D. J. (2013) · Aging Cell · doi:10.1111/acel.12062 · Cited by 162 · see citing works
Chronic fatigue syndrome and circulating cytokines: A systematic review
Blundell, S., Ray, K. K., Buckland, M., & White, P. D. (2015) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2015.07.004 · Cited by 159 · see citing works
Exercise therapy for people with sarcopenic obesity: myokines and adipokines as effective actors
Alizadeh Pahlavani, H. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.811751 · Cited by 145 · see citing works
Microglia in Aging and Alzheimer’s Disease: A Comparative Species Review
Edler, M. K., Mhatre-Winters, I., & Richardson, J. R. (2021) · Cells · doi:10.3390/cells10051138 · Cited by 126 · see citing works
Lee, K., Shin, K., Kim, G., Song, Y. C., Bae, E., Kim, I., Koh, C., & Kang, C. (2016) · Aging Cell · doi:10.1111/acel.12435 · Cited by 125 · see citing works
Calçada, D., Vianello, D., Giampieri, E., Sala, C., Castellani, G., de Graaf, A., Kremer, B., van Ommen, B., Feskens, E., Santoro, A., et al. (2014) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2014.01.004 · Cited by 97 · see citing works
Sarcopenic obesity: Myokines as potential diagnostic biomarkers and therapeutic targets?
Guo, A., Li, K., & Xiao, Q. (2020) · Experimental Gerontology · doi:10.1016/j.exger.2020.111022 · Cited by 83 · see citing works
Telomere shortening and immune activity in war veterans with posttraumatic stress disorder
Jergović, M., Tomičević, M., Vidović, A., Bendelja, K., Savić, A., Vojvoda, V., Rac, D., Lovrić-Čavar, D., Rabatić, S., Jovanovic, T., et al. (2014) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2014.06.010 · Cited by 67 · see citing works
Effect of age on chronic inflammation and responsiveness to bacterial and viral challenges
Elisia, I., Lam, V., Hofs, E., Li, M. Y., Hay, M., Cho, B., Brooks-Wilson, A., Rosin, M., Bu, L., Jia, W., et al. (2017) · PLOS ONE · doi:10.1371/journal.pone.0188881 · Cited by 34 · see citing works
- Authors
- Álvarez-Rodríguez, L., López-Hoyos, M., Muñoz-Cacho, P., & Martínez-Taboada, V. M.
- Affiliations
- Universidad de Cantabria (ES)
- Corresponding author
- Martínez-Taboada, Víctor Manuel
- Venue
- Cellular Immunology
- Publisher
- Elsevier BV
- Published
- 2012
- Volume
- 273
- Issue
- 2
- Pages
- 124-132
- ISSN
- 0008-8749 (ISSN-L)
- OpenAlex
- W2071079513
- Cited by
- 217
- References
- 41
- Citations by year
- 2026: 11 · 2025: 28 · 2024: 14 · 2023: 9 · 2022: 15 · 2021: 21 · 2020: 11 · 2019: 20 · 2018: 19 · 2017: 18 · 2016: 7 · 2015: 9 · 2014: 11 · 2013: 20 · 2012: 4
- FWCI
- 6.13
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cellular Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Fundación Marqués de Valdecilla
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Keywords
- aging, serum cytokines, inflammatory cytokines, IL-12p70, IL-1β, TNF-α, interleukin-6, IL-10, IL-17, monocytes, intracellular cytokine expression, healthy older adults, age-related inflammation
- MeSH terms
- Adult, Aged, Aged, 80 and over, Aging, Cells, Cultured, Enzyme-Linked Immunosorbent Assay, Female, Flow Cytometry, Humans, Male, Middle Aged, Monocytes, T-Lymphocytes, Cytokines, CD3 Complex, Lipopolysaccharide Receptors, Th1-Th2 Balance
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