Elevated levels of tumor necrosis factor alpha and mortality in centenarians.
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.


CONCLUSIONS
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.
Bruunsgaard
Helle
H
Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Denmark. infdishb@rh.dk
Andersen-Ranberg
Karen
K
Hjelmborg
Jacob v B
Jv
Pedersen
Bente Klarlund
BK
Jeune
Bernard
B
D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000378:metabolism / Q000401:mortality; D003704:Dementia / Q000378:metabolism / Q000401:mortality; D003718:Denmark / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008297:Male; D015999:Multivariate Analysis; D012141:Respiratory Tract Infections / Q000378:metabolism*; D012720:Severity of Illness Index; D013223:Statistics as Topic; D016019:Survival Analysis
D015415:Biomarkers; D015850:Interleukin-6; D016209:Interleukin-8; D002097:C-Reactive Protein