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.
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“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]
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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
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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
Self-citationChronic 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
Self-citationFranceschi, 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
Self-citationInflammation and immune dysfunction in Parkinson disease
Tansey, M. G., Wallings, R. L., Houser, M. C., Herrick, M. K., Keating, C. E., & Joers, V. (2022) · Nature Reviews Immunology · doi:10.1038/s41577-022-00684-6 · Cited by 1,382
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
Self-citation
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
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