Elevated levels of tumor necrosis factor alpha and mortality in centenarians

Am J Med. 2003 Sep;115(4):278-83. doi: 10.1016/s0002-9343(03)00329-2.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers / blood
  • C-Reactive Protein / metabolism
  • Cardiovascular Diseases / metabolism
  • Cardiovascular Diseases / mortality
  • Dementia / metabolism
  • Dementia / mortality
  • Denmark / epidemiology
  • Female
  • Follow-Up Studies
  • Humans
  • Interleukin-6 / metabolism
  • Interleukin-8 / metabolism
  • Male
  • Multivariate Analysis
  • Respiratory Tract Infections / metabolism*
  • Severity of Illness Index
  • Statistics as Topic
  • Survival Analysis


  • Biomarkers
  • Interleukin-6
  • Interleukin-8
  • C-Reactive Protein