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.
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.
Authors: Celia Quijano; Liu Cao; Maria M Fergusson; Hector Romero; Jie Liu; Sarah Gutkind; Ilsa I Rovira; Robert P Mohney; Edward D Karoly; Toren Finkel Journal: Cell Cycle Date: 2012-04-01 Impact factor: 4.534
Authors: Ming Xu; Tamara Tchkonia; Husheng Ding; Mikolaj Ogrodnik; Ellen R Lubbers; Tamar Pirtskhalava; Thomas A White; Kurt O Johnson; Michael B Stout; Vojtech Mezera; Nino Giorgadze; Michael D Jensen; Nathan K LeBrasseur; James L Kirkland Journal: Proc Natl Acad Sci U S A Date: 2015-11-02 Impact factor: 11.205