The DOI matches its Crossref record; 85 of the 85 references it cites were found in a registry or an index.
Cellular signaling in the aging immune system
Abstract
Causes for immunosenescence and inflamm-aging have to be established. Efficient function of the immune system requires homeostatic regulation from receptor recognition of antigenic challenge to cell responses and adaptation to its changing environment. It is reasonable to assume that one of the most important molecular causes of immunosenescence is alteration in the regulation of signaling pathways. Indeed, alterations in feed-forward and negative feedback (inhibitory) signaling have been highlighted in all cells involved in the immune response including short-lived (neutrophils) and long-lived (T lymphocytes) cells. These dysregulations tip the balance in favor of altered (less efficient) function of the immune system. In this review, we summarize our knowledge on signal transduction changes in the aging immune system and propose a unifying mechanism as one of the causes of immunosenescence. Modulation of these pathways with aging represents a major challenge to restore the immune response to functional levels.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
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?
In the citing paper
“Studies of human T cells have associated aging with changes in autophagy, in membrane properties to form rafts, and in reactive oxygen production (Fulop et al., 2014; Phadwal et al., 2012); however, these studies examined total T cell populations, irrespective of naive or memory phenotypes, and are therefore difficult to interpret.”
From Successful and Maladaptive T Cell Aging (2017) · cites this paper as Fulop et al., 2014
In the citing paper
“In almost all immune cells, one of the most prominent changes occurring with aging regards signaling, that is integrating all the molecular events converging from the surface receptors to an adequate cellular response [132].”
From Aging of the immune system: Focus on inflammation and vaccination (2016) · cites this paper as [132]
Citations
Cites
López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013) · Cell · doi:10.1016/j.cell.2013.05.039 · Cited by 14,982
Inflamm‐aging: An Evolutionary Perspective on Immunosenescence
FRANCESCHI, C., BONAFÈ, M., VALENSIN, S., OLIVIERI, F., DE LUCA, M., OTTAVIANI, E., & DE BENEDICTIS, G. (2000) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2000.tb06651.x · Cited by 5,358
Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling
Ray, P. D., Huang, B.-W., & Tsuji, Y. (2012) · Cellular Signalling · doi:10.1016/j.cellsig.2012.01.008 · Cited by 4,373
Molecular mechanisms of T cell co-stimulation and co-inhibition
Chen, L., & Flies, D. B. (2013) · Nature Reviews Immunology · doi:10.1038/nri3405 · Cited by 3,114
Smith-Garvin, J. E., Koretzky, G. A., & Jordan, M. S. (2009) · Annual Review of Immunology · doi:10.1146/annurev.immunol.021908.132706 · Cited by 2,144
Mitogen-activated protein kinases in innate immunity
Arthur, J. S. C., & Ley, S. C. (2013) · Nature reviews. Immunology · doi:10.1038/nri3495 · Cited by 1,898
Fueling Immunity: Insights into Metabolism and Lymphocyte Function
Pearce, E. L., Poffenberger, M. C., Chang, C.-H., & Jones, R. G. (2013) · Science · doi:10.1126/science.1242454 · Cited by 1,363
Age-dependent dysregulation of innate immunity
Shaw, A. C., Goldstein, D. R., & Montgomery, R. R. (2013) · Nature Reviews Immunology · doi:10.1038/nri3547 · Cited by 1,061
Causes, consequences, and reversal of immune system aging
Montecino-Rodriguez, E., Berent-Maoz, B., & Dorshkind, K. (2013) · Journal of Clinical Investigation · doi:10.1172/jci64096 · Cited by 793
Aging, frailty and age-related diseases
Fülöp, T., Larbi, A., Witkowski, J. M., McElhaney, J. E., Loeb, M. B., Mitnitski, A., & Pawelec, G. (2010) · Biogerontology · doi:10.1007/s10522-010-9287-2 · Cited by 687
Self-citation
Cited by
Sorted by citations
Items 101–158 of 158
Okuda, H., Shibata, H., Watanabe, T., Terazawa, K., Mori, K., Ueda, N., Ohashi, T., & Ogawa, T. (2022) · Cancers · doi:10.3390/cancers14225689 · Cited by 5
Monocyte alteration in elderly hip fracture healing: monocyte promising role in bone regeneration
Shema, C., Lu, Y., Wang, L., & Zhang, Y. (2024) · Immunity & Ageing · doi:10.1186/s12979-024-00413-8 · Cited by 8
Are There Reliable Biomarkers for Immunosenescence and Inflammaging?
Fülöp, T., Cohen, A. A., Wong, G. C. L., Witkowski, J. M., & Larbi, A. (2019) · Healthy ageing and longevity · doi:10.1007/978-3-030-24970-0_15 · Cited by 5
Self-citationThe role of inflammaging in the development of chronic diseases of older people
Witkowski, J. M., Bryl, E., & Fülöp, T. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-822569-1.00014-7 · Cited by 5
Self-citationThe P5 disulfide switch: taming the aging unfolded protein response
Mathew, A. (2015) · Cell Stress and Chaperones · doi:10.1007/s12192-015-0606-z · Cited by 5
Immunosenescence and Cancer Immunotherapy at Old Age: Basics
Fülöp, T., Witkowski, J. M., Hirokawa, K., Larbi, A., & Pawelec, G. (2018) · Springer eBooks · doi:10.1007/978-3-319-44870-1_77-1 · Cited by 4
Self-citationImmunosenescence and Cancer Immunotherapy at Old Age: Basics
Fülöp, T., Witkowski, J. M., Hirokawa, K., Larbi, A., & Pawelec, G. (2020) · Springer eBooks · doi:10.1007/978-3-319-57415-8_77 · Cited by 4
Self-citationPrahlad, V., & Chikka, M. R. (2018) · Wiley eBooks · doi:10.1002/9781118772034.ch3 · Cited by 4
Thomas‐Vaslin, V. (2019) · Acta Biotheoretica · doi:10.1007/s10441-019-09364-w · Cited by 4
Senescencia del sistema inmune y alteraciones relacionadas con el asma
Vega-Robledo, G. B., & Rico-Rosillo, M. G. (2017) · Revista Alergia México · doi:10.29262/ram.v64i2.264 · Cited by 3
Provost, G., Lavoie, F. B., Larbi, A., Ng, T., Ying, C., Chua, M. J., Fülöp, T., & Cohen, A. A. (2022) · Immunity & Ageing · doi:10.1186/s12979-022-00291-y · Cited by 3
Self-citationInflammaging and Immunosenescence
Fülöp, T., Pawelec, G., Cohen, A. A., Legault, V., Hirokawa, K., Larbi, A., Khalil, A., Franceschi, C., & Witkowski, J. M. (2024) · Springer eBooks · doi:10.1007/978-3-031-57361-3_10 · Cited by 2
Self-citationChoucair, K., Elliott, A., Oberley, M. J., Walker, P., Salama, A. K. S., Saeed, A., Mamdani, H. M., Uprety, D., El‐Deiry, W. S., Beltran, H., et al. (2025) · BMJ Oncology · doi:10.1136/bmjonc-2024-000551 · Cited by 2
Nutrition, aging, and requirements in the elderly
Elmadfa, I., & Meyer, A. L. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-818460-8.00005-8 · Cited by 3
Wang, L., Luo, J., Hu, H., Zhang, L., Li, Y., Ai, L.-M., Wang, Y.-L., Ma, Y., Mu, H.-Y., & Hou, Y. (2015) · PubMed Central · Cited by 2
Diversity of CD28null T Cells in the Elderly: A Glimpse in a Biological Adaptation of Aging
Griffin, P. C., Michel, J. J., & Vallejo, A. N. (2017) · Springer eBooks · doi:10.1007/978-3-319-64597-1_87-1 · Cited by 2
Role of Immunosenescence in Infections and Sepsis in the Elderly
Lesur, O., Fülöp, T., Castle, S. C., Larbi, A., Fortin, C. F., & Pawelec, G. (2019) · Springer eBooks · doi:10.1007/978-3-319-99375-1_48 · Cited by 2
Self-citationZeng, Y., Xue, T., Zhang, D., & Lv, M. (2023) · Combinatorial Chemistry & High Throughput Screening · doi:10.2174/1386207326666230619091603 · Cited by 2
Severe Sepsis, Pneumonia and Aging
Falade, O., & Yende, S. P. (2015) · WORLD SCIENTIFIC eBooks · doi:10.1142/9789814635011_0006 · Cited by 1
Wang, N., Wang, C., Wang, X., Meng, Y., Cui, S., Zhao, K., Jia, Y., & Kong, F. (2026) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2026.189587 · Cited by 1
Kyrklund, M., Kaski, H., Akhi, R., Nissinen, A. E. T., Kummu, O., Bergmann, U., Pussinen, P. J., Hörkkö, S., & Wang, C. (2021) · Innate Immunity · doi:10.1177/1753425920981133 · Cited by 1
Basso, M., Zago, D., Pozzetto, I., Vecchio, C. D., Franchin, E., Bello, F. D., Pagni, S., Fragaki, M., Biasolo, A., Manganelli, R., et al. (2021) · The Open Microbiology Journal · doi:10.2174/1874285802115010026 · Cited by 1
Signal Transduction Changes in T Cells with Aging
Fülöp, T., Page, A. Y. L., Dupuis, G., Fortin, C. F., Witkowski, J. M., & Larbi, A. (2019) · Springer eBooks · doi:10.1007/978-3-319-99375-1_35 · Cited by 1
Self-citationEffect of Intrinsic and Extrinsic Lipids on T Cell Signaling
Larbi, A., Aspray, E. C., Pawelec, G., Khalil, A., & Fülöp, T. (2019) · Springer eBooks · doi:10.1007/978-3-319-99375-1_69 · Cited by 1
Self-citationThe Complex Relationship Between Nutrition and Immunosenescence
Larbi, A., Lesourd, B., & Fülöp, T. (2019) · Springer eBooks · doi:10.1007/978-3-319-99375-1_65 · Cited by 1
Self-citationPawelec, G., & Müller, L. (2024) · Springer eBooks · doi:10.1007/978-3-030-74720-6_104 · Cited by 1
Stojić-Vukanić, Z., Pilipović, I., Arsenović-Ranin, N., Dimitrijević, M., & Leposavić, G. (2021) · Immunology Letters · doi:10.1016/j.imlet.2021.08.003 · Cited by 1
Diversity of CD28null T Cells in the Elderly: A Glimpse in a Biological Adaptation of Aging
Griffin, P. C., Michel, J. J., & Vallejo, A. N. (2019) · Springer eBooks · doi:10.1007/978-3-319-99375-1_87 · Cited by 1
Fülöp, T., Larbi, A., Khalil, A., Hirokawa, K., Cohen, A. A., & Witkowski, J. M. (2022) · Lessons from the ICU · doi:10.1007/978-3-030-94133-8_6 · Cited by 1
Self-citationImmune Aging, Autoimmunity, and Autoinflammation
Watad, ., McGonagle, D., Sellami, M., Amital, H., & Bragazzi, N. L. (2019) · Springer eBooks · doi:10.1007/978-3-319-69892-2_439-1 · Cited by 1
Wang, L., Luo, J., Hu, H., Zhang, L., Li, Y., Ai, L.-M., Wang, Y.-L., Ma, Y., Mu, H.-Y., & Hou, Y. (2015) · PubMed Central · Cited by 2
La ausencia de CD38 induce un fenotipo autoinmune en el ratón C57BL/6 CD38-/- de edad avanzada
Domínguez-Pantoja, M. (2014)
Cell-Mediated Immunity to the Pneumococcus
Finn, A. H. R., & Malley, R. (2015) · Elsevier eBooks · doi:10.1016/b978-0-12-410530-0.00022-3
Immunosénescence : vieillissement « et » ou « du » système immunitaire
Poli, C., Beauvillain, C., Jeannin, P., Rénier, G., & Chevailler, A. (2016) · Revue Francophone des Laboratoires · doi:10.1016/s1773-035x(16)30281-7
Immune system changes and immunosenescence
Pawelec, G., Müller, L., Fülöp, T., & Dunn‐Walters, D. K. (2017) · Oxford University Press eBooks · doi:10.1093/med/9780198701590.003.0045
Immunological Methods and the Concept of Inflammaging in the Study of Human Aging
Fülöp, T., Pawelec, G., Witkowski, J. M., Cohen, A. A., Fortin, C. F., Page, A. Y. L., Garneau, H., Dupuis, G., & Larbi, A. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-811353-0.00004-x
Self-citationMacián, F. (2018) · Springer eBooks · doi:10.1007/978-3-319-64597-1_112-1
The Complex Relationship Between Nutrition and Immunosenescence
Larbi, A., Lesourd, B., & Fülöp, T. (2018) · Springer eBooks · doi:10.1007/978-3-319-64597-1_65-1
Self-citationPawelec, G., & Müller, L. (2021) · Springer eBooks · doi:10.1007/978-3-030-01782-8_104-1
Immune Aging, Autoimmunity, and Autoinflammation
Watad, ., McGonagle, D., Sellami, M., Amital, H., & Bragazzi, N. L. (2021) · Springer eBooks · doi:10.1007/978-3-030-22009-9_439
Signal Transduction Changes in T-Cells with Aging
Fülöp, T., Page, A. Y. L., Dupuis, G., Fortin, C. F., Witkowski, J. M., & Larbi, A. (2018) · Springer eBooks · doi:10.1007/978-3-319-64597-1_35-1
Self-citationWitkowski, J. M., & Fülöp, T. (2018) · Springer eBooks · doi:10.1007/978-3-319-64597-1_13-1
Self-citationMacián, F. (2019) · Springer eBooks · doi:10.1007/978-3-319-99375-1_112
Witkowski, J. M., & Fülöp, T. (2019) · Springer eBooks · doi:10.1007/978-3-319-99375-1_13
Self-citationEffect of Intrinsic and Extrinsic Lipids on T-Cell Signaling
Larbi, A., Aspray, E. C., Pawelec, G., Khalil, A., & Fülöp, T. (2018) · Springer eBooks · doi:10.1007/978-3-319-64597-1_69-1
Self-citationProvost, G., Lavoie, F. B., Larbi, A., Ng, T., Ying, C. T. T., Chua, M., Fülöp, T., & Cohen, A. A. (2022) · Research Square · doi:10.21203/rs.3.rs-1401703/v1
Self-citationRole of Immunosenescence in Infections and Sepsis in the Elderly
Lesur, O., Fülöp, T., Castle, S. C., Larbi, A., Fortin, C. F., & Pawelec, G. (2017) · Springer eBooks · doi:10.1007/978-3-319-64597-1_48-1
Self-citationInterleukin-10 augments human endogenous retroviral E1B variant of cd5 in aged T cells
Singh, B., Kumari, S., Kureel, A. K., Shah, A., Katiyar, S., Chaturvedi, C. P., Singh, K., & Rai, A. K. (2025) · Blood Research · doi:10.1007/s44313-025-00080-8
Combined immunodeficiency in elderly persons with COPD as a manifestation of immune aging
Pirogova, A. I., Lomtatidze, L. V., & Filippov, E. F. (2025) · Russian Journal of Immunology · doi:10.46235/1028-7221-17267-cii
Provost, G., Lavoie, F. B., Larbi, A., Ng, T., Ying, C., Chua, M., Fülöp, T., & Cohen, A. A. (2022) · Figshare · doi:10.6084/m9.figshare.20438160
Self-citationProvost, G., Lavoie, F. B., Larbi, A., Ng, T., Ying, C., Chua, M., Fülöp, T., & Cohen, A. A. (2022) · Figshare · doi:10.6084/m9.figshare.20438166
Self-citationCarroll, M., & DeWitt, J. C. (2024) · Elsevier eBooks · doi:10.1016/b978-0-323-95488-4.00164-9
Provost, G., Lavoie, F. B., Larbi, A., Ng, T., Ying, C., Chua, M., Fülöp, T., & Cohen, A. A. (2022) · Figshare · doi:10.6084/m9.figshare.20438163
Self-citationAutio, A., Nevalainen, T., Mishra, B. H., Jylhä, M., Flinck, H., & Hurme, M. (2020) · Figshare · doi:10.6084/m9.figshare.12299504
Cuppen, J. J. M., & Savelkoul, H. F. J. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms27010143 · Cited by 1
Niu, X., Nur, Z., Xie, W., Sun, Y., Wang, L. F., & Zheng, Y. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1781004 · Cited by 1
Metadata
- Authors
- Fulop, T., Le Page, A., Fortin, C., Witkowski, J. M., Dupuis, G., & Larbi, A.
- Affiliations
- Université de Sherbrooke (CA)
- Gdańsk Medical University (PL)
- Agency for Science, Technology and Research (SG)
- Venue
- Current Opinion in Immunology
- Publisher
- Elsevier BV
- Published
- 2014-08
- Volume
- 29
- Pages
- 105-111
- ISSN
- 0952-7915 (ISSN-L)
- OpenAlex
- W2049865778
- Cited by
- 158
- References
- 85
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 10 · 2023: 4 · 2022: 16 · 2021: 14 · 2020: 13 · 2019: 14 · 2018: 16 · 2017: 20 · 2016: 17 · 2015: 20 · 2014: 6
- FWCI
- 2.05
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Current Opinion in Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Canadian Institutes of Health Research (106634, 106701)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- immunosenescence, inflammaging, signal transduction, aging immune system, negative feedback signaling, feed-forward signaling, T cells, neutrophils, immune homeostasis
- MeSH terms
- Aging, Animals, Humans, Neutrophils, Oxidation-Reduction, Receptors, Antigen, T-Cell, T-Lymphocytes, Signal Transduction
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