Cited by 334Genetics, Aging, and Longevity in Model OrganismsInflammatory Biomarkers in Disease PrognosisFrailty in Older Adults

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Elevated levels of tumor necrosis factor alpha and mortality in centenarians

Bruunsgaard, Helle, Andersen-Ranberg, Karen, Hjelmborg, Jacob v.B, Pedersen, Bente Klarlund, Jeune, Bernard·2003·The American Journal of Medicine

DOI 10.1016/s0002-9343(03)00329-2

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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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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)
ORCID: Hjelmborg, Jacob v.B
Pedersen, Bente Klarlund
Venue: The American Journal of Medicine
Publisher: Elsevier BV
Published: 2003-09
Volume: 115
Issue: 4
Pages: 278-283
ISSN: 0002-9343 (ISSN-L)
DOI: 10.1016/s0002-9343(03)00329-2
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
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
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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Elevated levels of tumor necrosis factor alpha and mortality in centenarians

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