Thymic function failure and C-reactive protein levels are independent predictors of all-cause mortality in healthy elderly humans

Abstract

Relationship between thymic function and elderly survival has been suspected, despite the fact that formal proof is elusive due to technical limitations of thymic function-related markers. The newly described sj/β-TREC ratio allows now, by overcoming these limitations, an accurate measurement of thymic output in elderly humans. Thus, the aim of this study was to determine the impact of thymic function and inflammatory markers on healthy elderly human survival. Healthy volunteers (n = 151), aged over 65, were asked to participate (CARRERITAS cohort). Subjects were excluded if diagnosed of dementia or, during the last 6 months, had clinical data of infection, hospital admission, antitumor therapy, or any treatment that could influence the immune status. Thymic function (sj/β-TREC ratio), CD4:CD8 T cell ratio, C-reactive protein, interleukin-6, and neutrophilia were determined from basal samples. All basal variables and age were associated with 2-year all-cause mortality. Multivariate analysis showed that only thymic function and C-reactive protein were independently associated with time to death. In conclusion, we show, for the first time, the direct role of thymic function in human survival. C-reactive protein raise is also a marker of mortality in the healthy elderly, in a thymic-independent way.

Fig. 1

Kaplan–Meier curves for all time-to-event analyses were analyzed for all statistically significant variables from the bivariate Cox proportional-Hazards bivariate regression. All continuous variables were dichotomized using the median as cutoff value. Log rank-test bivariate analysis was performed to assess statistical differences among the curves

Fig. 2

Kaplan–Meier curves for all time-to-event analyses were analyzed for CRP and thymic function. Different groups were made with intended values after the COR analysis-defined cutoffs related with higher death risk for a C-reactive protein and b thymic function. c Using these values, the CRT index accurately identifies individuals at different risk levels. The number of subjects at risk are shown in basal (0 weeks) and after 6 months (24 weeks), 1 year (48 weeks), 18 months (72 weeks), and 2 years (96 weeks)