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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An age-related decrease in absolute number of peripheral blood naïve T cells is consistently found in all studies and in different human populations.
“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]
A variety of phenomena have been proposed to contribute to the age-related heightened inflammatory state, including redox stress, immuno- and endocrine senescence, DNA damage, epigenetic modification, and a distortion of gut microbial homeostasis associated with increased levels of circulating endotoxin.
“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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- 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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