Hallmarks of human “immunosenescence”: adaptation or dysregulation?
Open accessAbstract
Is immunosenescence an intrinsic ageing process leading to dysregulation of immunity or an adaptive response of the individual to pathogen exposure? Age-associated differences in bone marrow immune cell output and thymic involution suggest the former. Accepted hallmarks of immunosenescence (decreased numbers and percentages of peripheral naïve T cells, especially CD8 + cells, and accumulations of memory T cells, especially late-stage differentiated CD8+ cells) suggest the latter, viewed as the result of depletion of the reservoir of naïve cells over time by contact with pathogens and their conversion to memory cells, the basis of adaptive immunity. Thymic involution beginning early in life limits the generation of naive cells such that the adult is believed to rely to a great extent on the naïve cell pool produced mostly before puberty. Thus, these hallmarks of immunosenescence would be markedly affected by the history of the individual´s exposure to pathogens. It would be predicted that in modern industrialized populations, the cumulative effects of antigenic "stressors" would be lower than in less hygienic societies, whereas intrinsic processes might be more similar in different populations. Identifying such stressors and taking steps to nullify their impact could therefore result in delayed immunosenescence and contribute significantly to improving public health. Here, I discuss some of the available data bearing on this prediction.
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Several factors, such as genetics, nutrition, exercise, previous exposure to microorganisms, biological and cultural sex, and HCMV status, can influence immunosenescence.
“Several factors, such as genetics, nutrition, exercise, previous exposure to microorganisms, biological and cultural sex, and human cytomegalovirus (HCMV) status can influence immunosenescence (3, 6–11).”
From Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention (2019) · cites this paper as [6]
A number of longitudinal studies of octogenarians and non-agenarians performed in Sweden defined an immunological risk phenotype (IRP).
“As critically reviewed by (3, 6, 16), a number of longitudinal studies of octogenarians and non-agenarians performed in Sweden defined an immunological risk phenotype (IRP).”
From Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention (2019) · cites this paper as [6]
Persistent HCMV infection leads to chronic stimulation of CD8 T cells, which expand clonally showing an effector memory phenotype characterized by low CD28 expression.
“In fact, as discussed below, persistent HCMV infection leads to chronic stimulation of CD8 T cells, which expand clonally showing an effector memory phenotype characterized by low CD28 expression.”
From Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention (2019) · cites this paper as [6]
The IRP was not confirmed in the Leiden 85-Plus study.
“However, this IRP was not confirmed in the Leiden 85-Plus study, a prospective population-based cohort study of individuals at the age of 85 years living in Leiden (NL).”
From Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention (2019) · cites this paper as [6]
Participants with the reversal of CD4/CD8 T-cell ratio, a reduced proliferative response to mitogenic stimuli, and severe reduced B cells number showed reduced survival.
“Participants with the reversal of CD4/CD 8 T-cell ratio, a reduced proliferative response to mitogenic stimuli, and severe reduced B cells number showed reduced survival.”
From Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention (2019) · cites this paper as [6]
Immune parameters associated with survival may vary in diverse populations at different ages.
“Thus, immune parameters associated with survival may vary in diverse populations at different ages (6).”
From Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention (2019) · cites this paper as [6]
The IRP was present in around 15% of 85-year-olds in these studies at baseline.
“The IRP was present in around 15% of 85-years-olds in these studies at baseline.”
From Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention (2019) · cites this paper as [6]
Follow-up of 2-, 4-, and 6-years mortality revealed significantly higher all-cause mortality in the IRP group than in the majority of other octogenarians and non-agenarians.
“Follow-up of 2-, 4-, and 6-years mortality revealed significantly higher all-cause mortality in the IRP group than in the majority of other octogenarians and non-agenarians.”
From Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention (2019) · cites this paper as [6]
HCMV seropositivity is closely related to the reversal of CD4/CD8 T-cell ratio.
“Subsequently, the data were implemented and related to HCMV seropositivity, because HCMV seropositivity is closely related to the reversal of CD4/CD 8 T-cell ratio.”
From Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention (2019) · cites this paper as [6]
Immunosenescence is only partially explained by organismal and cellular senescence.
“Mechanistically, immunosenescence is only partially explained by organismal and cellular senescence.”
From Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention (2019) · cites this paper as [6]
These hallmarks of immunosenescence would be markedly affected by the history of the individual exposure to pathogens.
“Therefore, these hallmarks of immunosenescence would be markedly affected by the history of the individual exposure to pathogens (6, 23).”
From Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention (2019) · cites this paper as [6]
The main barrier to better clarity remains the wide heterogeneity among human beings, linked to different life-style and genetic factors that influence the rate of immunosenescence.
“The main barrier to better clarity remains the wide heterogeneity among human beings, linked to different life-style and genetic factors that influence the rate of immunosenescence (6, 10, 11, 82).”
From Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention (2019) · cites this paper as [6]
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- Authors
- Pawelec, G.
- Affiliations
- University of Tübingen (DE)
- Corresponding author
- Pawelec, Graham
- ORCID
- Pawelec, Graham
- Venue
- Immunity & Ageing
- Published
- 2012-07-25
- Volume
- 9
- Issue
- 1
- Pages
- 15-15
- ISSN
- 1742-4933 (ISSN-L)
- PMC
- PMC3416738
- OpenAlex
- W2156305960
- Cited by
- 257
- References
- 25
- Citations by year
- 2026: 7 · 2025: 21 · 2024: 20 · 2023: 20 · 2022: 24 · 2021: 30 · 2020: 25 · 2019: 23 · 2018: 18 · 2017: 17 · 2016: 11 · 2015: 13 · 2014: 11 · 2013: 17
- FWCI
- 5.73
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Immunity & Ageing (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- European Commission (FP7259679, 259679)
- Deutsche Forschungsgemeinschaft (PA 361/14-1, DFG PA 361/14-1, /14-1)
- Bundesministerium für Bildung und Forschung
- 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, aging, thymic involution, naive T cells, CD8+ T cells, memory T cells, pathogen exposure, hygiene hypothesis, adaptive immunity
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