Elevated levels of tumor necrosis factor alpha and mortality in centenarians
Abstract
Background Aging is accompanied by low-grade inflammation. Tumor necrosis factor (TNF) alpha initiates the cytokine cascade, and high levels are associated with dementia and atherosclerosis in persons aged 100 years. We hypothesized that TNF-alpha was also a prognostic marker for all-cause mortality in these persons.Methods We enrolled 126 subjects at or around the time of their 100th birthday. Plasma levels of TNF-alpha, interleukin (IL)-6, IL-8, and C-reactive protein were measured at baseline, and we determined the associations between the markers of inflammation and mortality during the subsequent 5 years.Results Only 9 subjects were alive after 5 years. Elevated levels of TNF-alpha were associated with mortality in both men and women (hazard ratio = 1.34 per SD of 2.81 pg/mL; 95% confidence interval: 1.12 to 1.60, P = 0.001). Levels of IL-6 and IL-8 did not affect survival; levels of C-reactive protein were not associated with mortality when levels of TNF-alpha were included in the analysis. Dementia and cardiovascular diseases represented the major causes of comorbid conditions at baseline. TNF-alpha was still associated with mortality in multivariate models that included these parameters as confounders.Conclusion TNF-alpha was an independent prognostic marker for mortality in persons aged 100 years, suggesting that it has specific biological effects and is a marker of frailty in the very elderly.
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TNFα production increases with age and could contribute to diminished germinal center formation.
“TNFα production also increases as we age and could contribute to this observed phenotype161-163.”
From SARS-CoV-2, COVID-19 and the aging immune system (2021) · cites this paper as [162]
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- Authors
- Bruunsgaard, H., Andersen-Ranberg, K., Hjelmborg, J. V. B., Pedersen, B. K., & Jeune, B.
- Affiliations
- University of Southern Denmark (DK)
- University of Copenhagen (DK)
- Venue
- The American Journal of Medicine
- Publisher
- Elsevier BV
- Published
- 2003-09
- Volume
- 115
- Issue
- 4
- Pages
- 278-283
- ISSN
- 0002-9343 (ISSN-L)
- OpenAlex
- W2000119824
- Cited by
- 325
- References
- 36
- Citations by year
- 2026: 7 · 2025: 19 · 2024: 16 · 2023: 16 · 2022: 17 · 2021: 23 · 2020: 11 · 2019: 14 · 2018: 12 · 2017: 12 · 2016: 15 · 2015: 14 · 2014: 13 · 2013: 13 · 2012: 11
- FWCI
- 3.89
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The American Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- University of Southern Denmark Research Portal (University of Southern Denmark) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Oncology › Inflammatory Biomarkers in Disease Prognosis
- Health Sciences › Medicine › Geriatrics and Gerontology › Frailty in Older Adults
- Keywords
- TNF-α, centenarians, all-cause mortality, low-grade inflammation, prognostic factors, interleukin-6, interleukin-8, C-reactive protein, frailty, oldest old, dementia, cardiovascular disease
- MeSH terms
- Aged, Aged, 80 and over, C-Reactive Protein, Cardiovascular Diseases, Dementia, Denmark, Female, Follow-Up Studies, Humans, Male, Respiratory Tract Infections, Severity of Illness Index, Statistics as Topic, Biomarkers, Interleukin-6, Multivariate Analysis, Survival Analysis, Interleukin-8
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