Overcoming immune dysfunction in the elderly: trained immunity as a novel approach
Open accessAbstract
People with advanced age have a higher susceptibility to infections and exhibit increased mortality and morbidity as the ability of the immune system to combat infections decreases with age. While innate immune cells display functional defects such as decreased phagocytosis, chemotaxis and cytokine production, adaptive immune cells exhibit reduced receptor diversity, defective antibody production and a sharp decline in naive cell populations. Successful responses to vaccination in the elderly are critical to prevent common infections such as influenza and pneumonia, but vaccine efficacy decreases in older individuals compared with young adults. Trained immunity is a newly emerging concept that showed that innate immune cells possess non-specific immunological memory established through epigenetic and metabolic reprogramming upon encountering certain pathogenic stimuli. Clinical studies suggest that trained immunity can be utilized to enhance immune responses against infections and improve the efficiency of vaccinations in adults; however, how trained immunity responses are shaped with advanced age is still an open question. In this review, we provide an overview of the age-related changes in the immune system with a focus on innate immunity, discuss current vaccination strategies for the elderly, present the concept of trained immunity and propose it as a novel approach to enhance responses against infections and vaccinations in the elderly population.
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The global population has been experiencing an aging trend, and the elderly population is more susceptible to infections, increased mortality, and morbidity.
“The global population has been experiencing an aging trend, and the elderly population is more susceptible to infections, increased mortality, and morbidity.368,369”
From Inflammation and aging: signaling pathways and intervention therapies (2023) · cites this paper as [369]
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Göçer, P., Gürer, Ü. S., Erten, N., Palanduz, Ş., Rayaman, E., Akarsu, B., Karan, A., & Çevikbaş, A. (2005) · Medical Principles and Practice · doi:10.1159/000088109 · Cited by 19 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- [170]Berendsen, M, Bles, P, de Bree, C et al. 2020. BCG vaccination induces innate immune training in adults over 50 years of age. Optimmunize: improving the beneficial effects of vaccines, Cambridge, UK. Abstract no: P3. Available at: https://coursesandconferences.wellcomegenomecampus.org/wp-content/uploads/2020/02/Optimmunize-Abstract-Book-v2.pdf
Cited by
Sorted by citations
Inflammation and aging: signaling pathways and intervention therapies
Li, X., Li, C., Zhang, W., Wang, Y., Qian, P., & Huang, H. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01502-8 · Cited by 1,443 · see citing works
“DISCUSSION The global population has been experiencing an aging trend, and the elderly population is more susceptible to infections, increased mortality, and morbidity.(368,369) Chronic inflammation appears to be closely linked to aging, and this review focuses on inflammaging, providing an overview of the molecular,…”
BackgroundImmunology of aging: the birth of inflammaging
Fulop, T., Larbi, A., Pawelec, G., Khalil, A., Cohen, A. A., Hirokawa, K., Witkowski, J. M., & Franceschi, C. (2021) · Clinical Reviews in Allergy & Immunology · doi:10.1007/s12016-021-08899-6 · Cited by 464 · see citing works
The Causes and Consequences of Trained Immunity in Myeloid Cells
Bhargavi, G., & Subbian, S. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1365127 · Cited by 62 · see citing works
Roadmap for alleviating the manifestations of ageing in the cardiovascular system
Liberale, L., Tual-Chalot, S., Sedej, S., Ministrini, S., Georgiopoulos, G., Grunewald, M., Bäck, M., Bochaton-Piallat, M.-L., Boon, R. A., Ramos, G. C., et al. (2025) · Nature Reviews Cardiology · doi:10.1038/s41569-025-01130-5 · Cited by 59 · see citing works
Self-citation
- Authors
- Bulut, O., Kilic, G., Domínguez-Andrés, J., & Netea, M. G.
- Affiliations
- Radboud University Nijmegen (NL)
- Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center , GA Nijmegen, The Netherlands
- University of Bonn (DE)
- Corresponding author
- Netea, Mihai G
- Venue
- International Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2020-08-07
- Volume
- 32
- Issue
- 12
- Pages
- 741-753
- ISSN
- 0953-8178 (ISSN-L)
- 1460-2377
- PMC
- PMC7680842
- OpenAlex
- W3047982948
- Cited by
- 99
- References
- 181
- Citations by year
- 2026: 14 · 2025: 15 · 2024: 29 · 2023: 12 · 2022: 12 · 2021: 14 · 2020: 3
- FWCI
- 1.00
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- International Immunology (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion, other-oa)
- Funders
- Netherlands Organization for Scientific Research
- European Research Council (#833247)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- trained immunity, immunosenescence, aging immune system, innate immunity, vaccine response in the elderly, epigenetic reprogramming, metabolic reprogramming, influenza vaccination, pneumonia vaccination
- MeSH terms
- Aging, Animals, Humans, Immunity, Innate
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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