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Understanding immunosenescence to improve responses to vaccines
Open accessAbstract
In the older adult, the benefits of vaccination to prevent infectious disease are limited, mainly because of the adaptive immune system's inability to generate protective immunity. The age-dependent decrease in immunological competence, often referred to as 'immunosenescence', results from the progressive deterioration of innate and adaptive immune responses. Most insights into mechanisms of immunological aging have been derived from studies of mouse models. In this Review, we explore how well such models are applicable to understanding the aging process throughout the 80-100 years of human life and discuss recent advances in identifying and characterizing the mechanisms that underlie age-associated defective adaptive immunity in humans.
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“These and other models, for which it has been shown that accelerated aging depends, at least partly, on cellular senescence, are valuable for studying the impact of senescence on health and lifespan”
From Guidelines for minimal information on cellular senescence experimentation in vivo (2024) · cites this paper as [100]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Mouse models of rapid telomere shortening, dysfunctional mitosis or impaired DNA repair (Terc, BubR1, and Ercc1 mutant mice, respectively), display high levels of cellular senescence and accelerated aging86,99,100.”
From Guidelines for minimal information on cellular senescence experimentation in vivo (2024) · cites this paper as [100]
Experimental — accuracy not yet measuredIn the citing paper
“Evidence of waning adaptive immunity is already apparent in mid adulthood, as early as at the age of 50 years, with increasing clinical relevance in the 7th–10th decade of life”
From Successful and Maladaptive T Cell Aging (2017) · cites this paper as Goronzy and Weyand, 2013
In the citing paper
“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 [23]
In the citing paper
“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 [23]
In the citing paper
“The hallmarks of immunosenescence include: (i) a reduced ability to respond to new antigens; (ii) the accumulation of memory T cells; (iii) a lingering level of low-grade inflammation termed “inflamm-aging.””
From Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention (2019) · cites this paper as [23]
In the citing paper
“T cell clones specific for HCMV dominate the repertoire in the older people and contribute to the contraction in diversity in the memory compartment (23).”
From Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention (2019) · cites this paper as [23]
In the citing paper
“In contrast, high frequencies of antigen-specific T cells reactive to HCMV persist throughout life.”
From Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention (2019) · cites this paper as [23]
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“Immunosenescence reflects a progressive decline in both innate and adaptive immune competence, reducing the overall fitness of the immune system and its ability to respond to new antigens [72, 80].”
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“Moreover, the decline in the immune system fitness with age is thought to contribute to reduced vaccine efficacy in humans and mice (Bajaj et al., 2021; Franceschi et al., 2000; Frasca and Blomberg, 2016; Goronzy and Weyand, 2013; Weinberger et al., 2008).”
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IMMUNOLOGICAL MEMORY: THE ROLE OF REGULATORY CELLS (TREGS)
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“Identification of individuals with reduced vaccine responsiveness is vital for the strategic implementation of targeted vaccination programs to ensure their protection 6–8 .”
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“This ultimately contributes to increased susceptibility to infections, reduced vaccine efficacy, and a higher risk of autoimmunity and inflammation-related diseases in the elderly [31, 50].”
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“32 The decrease in CD55+EVs in the older adult population may contribute to these age-related changes.”
Metadata
- Authors
- Goronzy, J. J., & Weyand, C. M.
- Affiliations
- Stanford Medicine (US)
- VA Palo Alto Health Care System (US)
- Corresponding author
- Goronzy, Jörg J
- Venue
- Nature Immunology
- Published
- 2013-04-18
- Volume
- 14
- Issue
- 5
- Pages
- 428-436
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- PMC
- PMC4183346
- OpenAlex
- W1992431343
- Cited by
- 827
- References
- 115
- Citations by year
- 2026: 66 · 2025: 62 · 2024: 89 · 2023: 76 · 2022: 61 · 2021: 83 · 2020: 58 · 2019: 68 · 2018: 46 · 2017: 59 · 2016: 53 · 2015: 53 · 2014: 38 · 2013: 15
- FWCI
- 4.65
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Nature Immunology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute (P01HL058000, R01HL117913)
- National Eye Institute (R01EY011916)
- National Institute of Allergy and Infectious Diseases (R01AI044142, U01AI089859, R01AI44142, R01AI108906, U19AI090019, R01AI108891, U19AI057266)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR042527)
- 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 › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- immunosenescence, immunological aging, older adults, vaccine response, innate immune dysregulation, mouse models of aging
- MeSH terms
- Aged, Aged, 80 and over, Aging, Animals, Communicable Disease Control, Humans, Immunocompetence, Vaccination, Vaccines, Cellular Senescence, Mice, Adaptive Immunity
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