Impaired innate immunity predicts frailty in old age. The Leiden 85-plus study
Abstract
Aging is associated with an impaired capacity of the immune system to respond properly to danger signals, such as infection and cancer. Here, we provide evidence that an impaired innate immune response, as measured by a low production capacity of pro- and anti-inflammatory cytokines upon ex vivo standardized danger signalling with bacterial LPS, is predictive for frailty in elderly people: participants who at age 85-year produced low levels of LPS-induced IL-1beta, IL-6, TNF-alpha and IL-1Ra and IL-10, were found to have a more than 2-fold elevated overall mortality risk, independent of chronic illnesses (relative risk is 2.21, 95% confidence interval 1.27-3.82, P = 0.005), compared to peers with a higher production of any of the pro- and/or anti-inflammatory cytokines. A significant genetic association with the IL-10 promoter gene was found, indicating that people who are genetically predisposed low cytokine producers are at a higher risk of losing the capacity to respond properly to danger signals with aging. We conclude that a malfunctioning innate immune response predicts frailty in old age and is under specific (immuno-) genetic control.
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Reduced Toll-like receptor expression stalls cytokine and chemokine secretion by monocytes and macrophages and limits crosstalk with the adaptive immune system.
“Reduced Toll-like receptor expression stalls cytokine and chemokine secretion by monocytes and macrophages and limits crosstalk with the adaptive immune system234.”
From mRNA vaccines for infectious diseases: principles, delivery and clinical translation (2021) · cites this paper as [234]
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Self-citation
- Authors
- van den Biggelaar, A. H. J., Huizinga, T. W. J., de Craen, A. J. M., Gussekloo, J., Heijmans, B. T., Frölich, M., & Westendorp, R. G. J.
- Affiliations
- Leiden University Medical Center (NL)
- Venue
- Experimental Gerontology
- Publisher
- Elsevier BV
- Published
- 2004-09
- Volume
- 39
- Issue
- 9
- Pages
- 1407-1414
- ISSN
- 0531-5565 (ISSN-L)
- OpenAlex
- W2128275973
- Cited by
- 122
- References
- 32
- Citations by year
- 2026: 1 · 2025: 2 · 2023: 4 · 2022: 6 · 2021: 4 · 2020: 4 · 2019: 3 · 2018: 7 · 2017: 2 · 2016: 2 · 2015: 2 · 2014: 6 · 2013: 9 · 2012: 6
- FWCI
- 3.81
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Experimental Gerontology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Frailty in Older Adults
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- frailty, innate immunity, aging, cytokine production, lipopolysaccharide, IL-10, IL-1β, interleukin-6, TNF-α, IL-10 promoter, genetic association, mortality risk, immunosenescence
- MeSH terms
- Aged, Aged, 80 and over, Aging, Female, Follow-Up Studies, Humans, Immunity, Innate, Lipopolysaccharides, Male, Netherlands, Promoter Regions, Genetic, Survival Analysis, Cytokines, Frail Elderly, Interleukin-10, Genetic Predisposition to Disease
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