The DOI matches its Crossref record; 20 of the 20 references it cites were found in a registry or an index.
Human immunosenescence: the prevailing of innate immunity, the failing of clonotypic immunity, and the filling of immunological space
Abstract
According to the remodeling theory of aging we proposed several years ago, the current data on human immunosenescence depicts a complex scenario where clonotypical immunity deteriorates, while ancestral innate/natural immunity is largely conserved or even up-regulated with age. Under an evolutionary perspective, antigens are the cause of a persistent life-long antigenic stress, responsible for the accumulation of effector CD8+/CD28- T cells, the decrease of naive T cells (CD95-) and the marked shrinkage of T cell repertoire with age. Concomitantly, NK cytotoxicity, chemotaxis, phagocytosis and complement activities remain unaffected or negligibly affected, in comparison to clonotypical immunity. Thus, immunosenescence is not a random deteriorative phenomenon but appears to inversely recapitulate an evolutionary pattern. On the whole, immunosenescence can be envisaged as the result of the continuous challenge of the unavoidable exposure to a variety of potential antigens (viruses, bacteria, but also food and self molecules among others). From this perspective antigens are nothing else than a particular type of stressor and immunosenescence appears to be the price paid to immunological memory, i.e. one of the main characteristics of the most evolutionary recent and sophisticated type of immunity. Together with the age-related thymic involution, and the consequent age-related decrease of thymic output of new T cells, this situation leaves the body practically devoid of virgin T cells, and thus likely more prone to a variety of infectious and non infectious diseases.
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
“As previously stated, an age-related decrease in absolute number of peripheral blood naïve T cells is consistently found in all studies and in different human populations (22, 37).”
From Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention (2019) · cites this paper as [37]
In the citing paper
“A variety of phenomena have been proposed to contribute to this age-related heightened inflammatory state including redox stress [46], immuno- and endocrine senescence [47, 48], DNA damage [49], epigenetic modification [50], and a distortion of gut microbial homeostasis [51] that is associated with increased levels of circulating endotoxin [42].”
From Gut Microbiota Contribute to Age-Related Changes in Skeletal Muscle Size, Composition, and Function: Biological Basis for a Gut-Muscle Axis (2018) · cites this paper as [47]
Citations
Cites
Rufer, N., Brümmendorf, T. H., Kolvraa, S., Bischoff, C., Christensen, K., Wadsworth, L., Schulzer, M., & Lansdorp, P. M. (1999) · The Journal of Experimental Medicine · doi:10.1084/jem.190.2.157 · Cited by 709
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
Self-citationThe immunology of exceptional individuals: the lesson of centenarians
Franceschi, C., Monti, D., Sansoni, P., & Cossarizza, A. (1995) · Immunology Today · doi:10.1016/0167-5699(95)80064-6 · Cited by 535
Self-citationShortage of circulating naive CD8+ T cells provides new insights on immunodeficiency in aging
Fagnoni, F. F., Vescovini, R., Passeri, G., Bologna, G., Pedrazzoni, M., Lavagetto, G., Casti, A., Franceschi, C., Passeri, M., & Sansoni, P. (2000) · Blood · doi:10.1182/blood.v95.9.2860.009k35_2860_2868 · Cited by 515
Self-citationSansoni, P., Cossarizza, A., Brianti, V., Fagnoni, F. F., Snelli, G., Monti, D., Marcato, A., Passeri, G., Ortolani, C., & Forti, E. (1993) · Blood · doi:10.1182/blood.v82.9.2767.2767 · Cited by 457
MARIOTTI, S., FRANCESCHI, C., COSSARIZZA, A., & PINCHERA, N. (1995) · Endocrine Reviews · doi:10.1210/edrv-16-6-686 · Cited by 449
Self-citationExpansion of cytotoxic CD8 + CD28 − T cells in healthy ageing people, including centenarians
FAGNONI, F. F., VESCOVINI, R., MAZZOLA, M., BOLOGNA, G., NIGRO, E., LAVAGETTO, G., FRANCESCHI, C., PASSERI, M., & SANSONI, P. (1996) · Immunology · doi:10.1046/j.1365-2567.1996.d01-689.x · Cited by 362
Self-citationAging and Cancer: The Double‐Edged Sword of Replicative Senescence
Campisi, J. (1997) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.1997.tb05175.x · Cited by 254
Cossarizza, A., Ortolani, C., Paganelli, R., Barbieri, D., Monti, D., Sansoni, P., Fagiolo, U., Castellani, G., Bersani, F., Londei, M., et al. (1996) · Mechanisms of Ageing and Development · doi:10.1016/0047-6374(95)01691-0 · Cited by 253
Self-citationThyroid and other organ-specific autoantibodies in healthy ceritenarians
Mariotti, S., Barbesino, G., Caturegli, P., Giacomelli, T., Pinchera, A., Monti, D., Cossarizza, A., Franceschi, C., Sansoni, P., Passeri, G., et al. (1992) · The Lancet · doi:10.1016/0140-6736(92)91265-a · Cited by 227
Self-citation
Cited by
Sorted by citations
Items 401–491 of 491
Exercise, epigenetics, and aging
Chilton, W., Maier, M. C., Akinnibosun, O. A., O’Brien, B. J., & Charchar, F. J. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-820682-9.00002-5 · Cited by 1
Immune Suppression in Lung Disease: Lung Transplantation and HIV
McGinniss, J. E., Bernasconi, E., Twigg, H. L., & Morris, A. (2022) · Respiratory medicine · doi:10.1007/978-3-030-87104-8_10 · Cited by 1
Mitchell, W., & Aspinall, R. (2008) · CRC Press eBooks · doi:10.3109/9781420065985-2 · Cited by 1
Pathological Relevance of the Natural Immune System
Salvioli, S., Capri, M., Fumelli, C., Lescai, F., Franceschi, C., & Monti, D. (2005) · Neuroimmune biology · doi:10.1016/s1567-7443(05)80021-3 · Cited by 1
Self-citationThe oligoclonal expansion of T cells: The investigation of its stability over time
Chkalina, A. V., Zvyagin, I. V., Mamedov, I. Z., Britanova, O. V., Staroverov, D. B., & Lebedev, Y. B. (2010) · Russian Journal of Bioorganic Chemistry · doi:10.1134/s1068162010020081 · Cited by 1
The Immune System of the Older Horse
Adams, A. A., & Horohov, D. W. (2015) · Wiley eBooks · doi:10.1002/9781119086512.ch03 · Cited by 1
The Effects of Interleukin-10 on Skeletal Muscle Insulin Resistance and Myogenesis
Dağdeviren, S. (2016) · eScholarship@UMassChan · doi:10.13028/m2qp42 · Cited by 1
The role of parasites in the invasion ecology of Harmonia axyridis
Berry, K. M. (2017) · Stirling Online Research Repository (University of Stirling) · Cited by 1
Kruser, J. M., & Meyer, K. C. (2014) · Wiley eBooks · doi:10.1002/9781118396292.ch14 · Cited by 1
Juxtaposition of System Dynamics and Agent-Based Simulation for a Case Study in ImmunosenescencePreprint
Figueredo, G. P., Siebers, P., Aickelin, U., Whitbrook, A. M., & Garibaldi, J. M. (2015) · SSRN Electronic Journal · doi:10.2139/ssrn.2823219 · Cited by 1
Turner, J. E. (2016) · Springer eBooks · doi:10.1007/978-1-4614-6439-6_101906-1 · Cited by 1
Ilchmann-Diounou, H. (2019) · theses.fr (ABES) · doi:10.70675/77d1e895zc1e7z4ff0zab27z0432cc19c25d · Cited by 1
Müller‐Werdan, U., & Werdan, K. (2005) · Springer eBooks · doi:10.1007/3-540-26587-2_26 · Cited by 1
Cutaneous Manifestations of Aging and Immunodeficiency
Norman, R. A., & Henry, Z. (2014) · Springer eBooks · doi:10.1007/978-1-4471-6479-1_11
Warren, K. J. (2012) · Iowa State University Digital Repository (Iowa State University) · doi:10.31274/etd-180810-575
Growing Old and Immunity to Viruses
Nikolich‐Žugich, J., & Blackman, M. A. (2014) · ASM Press eBooks · doi:10.1128/9781555816872.ch32
Evaluating patient susceptibility in Clostridium difficile infection
Islam, J. (2013) · University of Brighton Repository (University of Brighton)
Barve, S. S., Ritchie, C. S., & McClain, C. J. (2004) · Humana Press eBooks · doi:10.1007/978-1-59259-391-0_30
Chapter 16 Context and Memory: A Lesson from Funes the Memorious
Neuman, Y. (2008) · Studies in multidisciplinarity · doi:10.1016/s1571-0831(07)00216-x
Simpson, R. J., & Spielmann, G. (2012) · Springer eBooks · doi:10.1007/978-1-4614-4776-4_10
The role of immune inhibitory receptors in age-associatedimmune decline
Macaulay, R. (2011) · UCL Discovery (University College London)
Lymphocytes Sub-Types and Functions in Centenarians as Models for Successful Ageing
Lugli, E., Troiano, L., Pinti, M., Nasi, M., Roat, E., Ferraresi, R., Bertoncelli, L., Gibellini, L., Nemes, E., & Cossarizza, A. (2009) · Springer eBooks · doi:10.1007/978-1-4020-9063-9_2
New strategies for allogeneic hematopoietic stem cell transplantation with umbilical cord
Gertow, J. (2013) · Figshare
Schwabl, H., & Vennos, C. (2011) · Deutsche Zeitschrift für Akupunktur · doi:10.1016/j.dza.2011.01.002
New Cells in Old Mice: The ABCs of Humoral Immunosenescence
Hao, Y. (2012) · Open Longevity Science · doi:10.2174/1876326x01206010112
Poschke, I. C. (2011) · Figshare
System Dynamics Modelling of the Processes Involving the Maintenance of the Naive T Cell RepertoirePreprint
Figueredo, G. P., Aickelin, U., & Whitbrook, A. M. (2016) · SSRN Electronic Journal · doi:10.2139/ssrn.2830382
Anti-Aging Medicine LiteratureWatch
Pawelec, G. (1998) · Rejuvenation Research · doi:10.1089/rej.1.1998.1.275
Immunity, Inflammation and infections during aging
Capri, M., Salvioli, S., Sevini, F., Cevenini, E., Pierini, M., Celani, L., Bucci, L., Ostan, R., Scurti, M., Mazzà, D., et al. (2007) · Springer eBooks · doi:10.1007/1-4020-5058-5_2
Self-citationInfluenza Infection in the Elderly
Moazzami, K., McElhaney, J. E., & Rezaei, N. (2013) · Springer eBooks · doi:10.1007/978-3-642-39495-9_18
Clinthorne, J. F. (2013) · Michigan State University Libraries · doi:10.25335/m5zq68
Hammond, E. R., & Treisman, G. J. (2008) · CRC Press eBooks · doi:10.3109/9781420065985-4
Discovery of Characteristics of Patients with Increased Level of
Yıldırım, P., & Holzinger, A. (2015)
Melanie, S., Cartier, L., & Dorman, S. C. (2015)
Convergence of Immunotherapy, Radiotherapy and Prostate Cancer: Challenges and Opportunities
Green, M. D., Feng, F. Y.-C., Mehra, R., & Spratt, D. E. (2017) · Immunotherapy · doi:10.2217/imt-2017-0059
Measuring Immunological Age: From T cell Repertoires to Populations
Naumova, E. N., Naumov, Y. N., & Gorski, J. (2017) · Springer eBooks · doi:10.1007/978-3-319-64597-1_171-1
The Biologic Interconnections Between Aging and Lymphoma
Falandry, C., Sarkozy, C., & Salles, G. A. (2017) · Springer eBooks · doi:10.1007/978-3-319-44870-1_78-1
Pizza, Milano, W. D., Padricelli, U., & Capasso, A. (2017)
The effect of aging on the immune response to vaccination in the horse
Fermaglich, D. H. (2003) · doi:10.31390/gradschool_theses.2499
Louzada, E. R. (2017) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.89.2017.tde-28112017-160051
Effects of habitual exercise on saliva immunoglobulin A in older adults
Fart, F. (2014) · KTH Publication Database DiVA (KTH Royal Institute of Technology)
Cheng, N., & Weng, N. (2018) · Springer eBooks · doi:10.1007/978-3-319-64597-1_108-1
Kim, K. (2019) · The Asian Journal of Kinesiology · doi:10.15758/ajk.2019.21.1.37
Compromised immunity and the microbiome: transplantation, cancer and HIV
Bernasconi, E., Aubert, J., Koutsokera, A., Nicod, L. P., & Twigg, H. L. (2019) · European Respiratory Society eBooks · doi:10.1183/2312508x.10031818
Kuremsky, C. A. (2018) · Louisiana State University · doi:10.31390/gradschool_theses.4845
Zouboulis, C. C. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-801238-3.11459-x
CNS lymphatics in health and disease
Yun, J. W., Alexander, J. S., & Gavins, F. N. E. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-815645-2.00005-8
Chronic stress and ageing : effects on immune function
Vitlić, A. (2014) · University of Birmingham Institutional Research Archive (University of Birmingham)
System Dynamics Modelling of the Processes Involving the Maintenance of the Naive T Cell RepertoirePreprint
Figueredo, G. P., Aickelin, U., & Whitbrook, A. M. (2010) · arXiv (Cornell University) · doi:10.48550/arxiv.1004.5215
Impact of cytomegalovirus-infection on ageing of the immune system
Berg, S. (2020) · Utrecht University Repository (Utrecht University) · doi:10.33540/66
Engagement in Leisure Activities Predicts the Inflammatory Response to Acute Psychosocial Stress
Hanlin, L. C. (2012) · Brandeis Institutional Repository · doi:10.48617/etd.758
Fauce, S. R., & Effros, R. B. (2008) · Springer eBooks · doi:10.1007/978-0-387-76842-7_4
Impact of physical activity on immune function and inflammation in the elderly
Bartlett, D. B. (2014) · University of Birmingham Institutional Research Archive (University of Birmingham)
Christopher Nicholson BA (Hons), M. (. N. (2007) · Heart failure · doi:10.1002/9780470988107.refs
Anti-Aging Medicine LiteratureWatch
(2000) · Rejuvenation Research · doi:10.1089/10945450050164808
Anti-Aging Medicine LiteratureWatch
Pawelec, G. (2000) · Rejuvenation Research · doi:10.1089/rej.1.2000.3.207
Bucci, L., Ostan, R., Capri, M., Salvioli, S., Cevenini, E., Celani, L., Monti, D., & Franceschi, C. (2009) · Springer eBooks · doi:10.1007/978-1-4020-9063-9_45
Self-citationAllergy and Immunology of the Aging Lung
Hoyte, F. C. L., & Katial, R. K. (2011) · Humana Press eBooks · doi:10.1007/978-1-60761-727-3_2
Turner, J. E. (2020) · Springer eBooks · doi:10.1007/978-3-030-39903-0_101906
The Biologic Interconnections Between Aging and Lymphoma
Falandry, C., Sarkozy, C., & Salles, G. A. (2020) · Springer eBooks · doi:10.1007/978-3-319-57415-8_78
Faculty Opinions recommendation of Telomeres, aging and exercise: guilty by association?
Savage, S. A. (2018) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.732200325.793545199
Immune compromise in the elderly
Müller, L., & Pawelec, G. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-816768-7.00046-6
Measuring Immunological Age: From T Cell Repertoires to Populations
Naumova, E. N., Naumov, Y. N., & Gorski, J. (2019) · Springer eBooks · doi:10.1007/978-3-319-99375-1_171
(2008) · Studies in multidisciplinarity · doi:10.1016/s1571-0831(07)00229-8
MPhil, P. J. G. (2007) · Wiley eBooks · doi:10.1002/9780470988121.refs
Girard, T. D. (2009) · Humana Press eBooks · doi:10.1007/978-1-60327-534-7_6
Banning, D. M. (2007) · Wiley eBooks · doi:10.1002/9780470692264.refs
(2014) · Elsevier eBooks · doi:10.1016/b978-1-907568-42-8.50016-2
Nitric Oxide, Gait Speed and Frailty Markers in Functionally Independent Oldest Old
Tommaso, A. B. D., Filho, C. D. M. A., Miranda, R. D., Mouro, M. G., Higa, E. M. S., & Cendoroglo, M. S. (2023) · Cardiology Research and Cardiovascular Medicine · doi:10.29011/2575-7083.100086
Silberman, J., Olagbiyan, M., & Moore, E. (2024) · Tissue Engineering Part A · doi:10.1089/ten.tea.2023.0327
Yaşlanma(ma)ya Multidisipliner Yaklaşım
Şenveli, M., Aydın, D., Küçükhüyük, Ş., Öztatlıcı, M., Hacıoğlu, C., Davran, F., Bacak, İ., Şimşek, M., Yıldız, H., Budak, S., et al. (2023) · Akademisyen Kitabevi eBooks · doi:10.37609/akya.2653
Molecular characterization of the human gut microbiota: the effect of aging
Biagi, E. (2010) · AMS Dottorato Institutional Doctoral Theses Repository (University of Bologna) · doi:10.6092/unibo/amsdottorato/2327
Sommer, C., Reamon-Buettner, S. M., Niehof, M., Hildebrand, C. B., Braun, A., Sewald, K., Dehmel, S., & Brandenberger, C. (2024) · Figshare · doi:10.6084/m9.figshare.26660729
Sommer, C., Reamon-Buettner, S. M., Niehof, M., Hildebrand, C. B., Braun, A., Sewald, K., Dehmel, S., & Brandenberger, C. (2024) · Figshare · doi:10.6084/m9.figshare.26660726
Age-specific relationships between immunity and life-history traits in a wild mammal
Cheynel, L. (2018) · theses.fr (ABES) · doi:10.70675/68380a80zb8a0z443fz9019z3fcc79a6f371
Millerand, M. (2020) · theses.fr (ABES) · doi:10.70675/d5e9dae6zd9d7z4a05z8fd2zf0ff4ffab0a6
Allergy and Immunology of the Aging Lung
Pathria, M., Hoyte, F. C. L., & Katial, R. K. (2026) · Respiratory medicine · doi:10.1007/978-3-032-29861-4_2
Toumi, H., Almhdie-Imjabbar, A., Ibrahim-Nasser, N., & Lespessailles, É. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27146332
Ying, J., Fang, Z., Zhang, C. L., Liu, X., Cui, J., Li, Z., & Tang, J. (2026) · Health care science · doi:10.1002/hcs2.70087
CORDOVA, C. O., Morais-Junior, G. S., Moraes, C. F., Camargos, E. F., Louzada, L. L., & Nóbrega, O. D. T. (2026) · Journal of Gerontology and Geriatrics · doi:10.3390/jgg74030030
Magnusiomyces Capitatus Infection in an Advanced-Age Elderly Patient: A Case Report
刘, 璐. (2026) · Advances in Clinical Medicine · doi:10.12677/acm.2026.16103485
Effects of nutritional supplements on the immune function of athletes
Muhamad, A. S. (2013) · Loughborough University Research Repository (Loughborough University)
Immune Compromise in the Elderly
Pawelec, G., & Müller, L. (2014) · Elsevier eBooks · doi:10.1016/b978-0-12-405546-9.00042-x
Metadata
- Authors
- Franceschi, C., Bonafè, M., & Valensin, S.
- Affiliations
- Istituto Nazionale di Riposo e Cura per Anziani (IT)
- University of Bologna (IT)
- Corresponding author
- Franceschi, Claudio
- ORCID
- Bonafè, Massimiliano
- Venue
- Vaccine
- Publisher
- Elsevier BV
- Published
- 2000-02
- Volume
- 18
- Issue
- 16
- Pages
- 1717-1720
- ISSN
- 0264-410X (ISSN-L)
- OpenAlex
- W1981560461
- Cited by
- 495
- References
- 20
- Citations by year
- 2026: 10 · 2025: 8 · 2024: 12 · 2023: 12 · 2022: 10 · 2021: 19 · 2020: 20 · 2019: 19 · 2018: 16 · 2017: 38 · 2016: 23 · 2015: 26 · 2014: 24 · 2013: 32 · 2012: 21
- FWCI
- 4.60
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Vaccine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- immunosenescence, innate immunity, T cell receptor repertoire, naive T cells, CD8+CD28- T cells, NK cell cytotoxicity, evolutionary immunology, thymic involution, immunological memory, aging
- MeSH terms
- Aged, Aged, 80 and over, Aging, Antigens, Cell Division, Biological Evolution, Humans, Immunity, Innate, Immunologic Memory, Lymphocyte Activation, Models, Biological, Stress, Physiological, T-Lymphocytes, Telomere
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
