Elevated levels of tumor necrosis factor alpha and mortality in centenarians

BackgroundAging is accompanied by low-grade inflammation. Tumor necrosis factor (TNF) α initiates the cytokine cascade, and high levels are associated with dementia and atherosclerosis in persons aged 100 years. We hypothesized that TNF-α was also a prognostic marker for all-cause mortality in these persons.MethodsWe enrolled 126 subjects at or around the time of their 100th birthday. Plasma levels of TNF-α, 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.ResultsOnly 9 subjects were alive after 5 years. Elevated levels of TNF-α 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-α were included in the analysis. Dementia and cardiovascular diseases represented the major causes of comorbid conditions at baseline. TNF-α was still associated with mortality in multivariate models that included these parameters as confounders.ConclusionTNF-α 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.