The DOI matches its Crossref record; 55 of the 56 references it cites were found in a registry or an index.
Biomarkers of immunosenescence within an evolutionary perspective: the challenge of heterogeneity and the role of antigenic load
Abstract
Under an evolutionary perspective, antigens can be considered nothing else than chronic stressors that constituted the major selective pressure for immune system emergence and evolution. In this review, recent data are discussed under the hypothesis that human immunosenescence is the consequence of the continuous attrition caused by chronic antigenic overload/stress. The advantage of this theoretical approach is that a unifying hypothesis is proposed, which tries to fill in the current gap between the conceptualizations concerning the mechanisms which counteract aging and favor longevity in invertebrates and vertebrates. The hypothesis is that the immune system is, at a higher level of biological organization and complexity, the counterpart of the anti-stress response network identified in invertebrates as the major determinant of survival. We argue that some of the most important characteristics of immunosenescence, i.e. the accumulation and the clonal expansion of memory and effector T cells, the reduction/exhaustion of naive T cells, and the shrinkage of T cell repertoire, are compatible with this assumption. Thus, immunosenescence can be envisaged as a global reduction of the "immunological space." Concomitantly, immunosenescence results in the progressive generation of cellular mosaicism which is the consequence of the heterogeneous replicative histories and telomere shortening of T and B cell subsets, as well as hemopoietic stem cells. Most of the parameters affected by immunosenescence appear to be under genetic control, and future research on biomarkers should address this point. On the whole, immunosenescence can be taken as a proof that the beneficial effects of the immune system, devoted to the neutralization of dangerous/harmful agents early in life and in adulthood, turn to be detrimental late in life, in a period largely not foreseen by evolution. This perspective fits with basic assumptions of evolutionary theories of aging, such as antagonistic pleiotropy.
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Metadata
- Authors
- Franceschi, C., Valensin, S., Fagnoni, F., Barbi, C., & Bonafè, M.
- Affiliations
- Istituto Nazionale di Riposo e Cura per Anziani (IT)
- University of Bologna (IT)
- University of Parma (IT)
- Corresponding author
- Franceschi, Claudio
- Venue
- Experimental Gerontology
- Publisher
- Elsevier BV
- Published
- 1999-12
- Volume
- 34
- Issue
- 8
- Pages
- 911-921
- ISSN
- 0531-5565 (ISSN-L)
- OpenAlex
- W1991422276
- Cited by
- 154
- References
- 56
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 6 · 2023: 6 · 2022: 7 · 2021: 5 · 2020: 8 · 2019: 5 · 2018: 6 · 2017: 2 · 2016: 2 · 2015: 8 · 2014: 3 · 2013: 3 · 2012: 6
- FWCI
- 0.60
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Experimental Gerontology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Keywords
- immunosenescence, biomarkers, chronic stress, immune system evolution, T cell exhaustion, T cell receptor repertoire, cellular mosaicism, telomere shortening, hematopoietic stem cells, antagonistic pleiotropy, evolutionary theory of aging, longevity
- MeSH terms
- Aging, Antigens, Biological Evolution, Humans, Immune System, Genetic Variation, Biomarkers
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