Association Between Body Weight and Telomere Length Is Predominantly Mediated Through C-Reactive Protein.

CONTEXT: Both obesity and inflammation are related to accelerated aging. It is not yet known whether inflammation mediates the effects of obesity on aging. OBJECTIVE: This work aims to dissect the direct effect of body mass index (BMI) and its indirect effect through C-reactive protein (CRP) on leukocyte telomere length (LTL) to determine the mediation effect of CRP on the BMI-LTL association. METHODS: The study cohort included 5451 adults (1404 Mexican American, 3114 White, and 933 Black individuals; 53.5% male; mean age = 49.2 years) from the 1999 to 2002 National Health and Nutrition Examination Survey. General mediation models were used to examine the mediation effect of CRP on the BMI-LTL association. RESULTS: After adjusting for age, race, sex, physical activity, alcohol use, and serum cotinine, the total effect of BMI on LTL was significant (standardized regression coefficient, ß = -.054, P < .001) without CRP included in the model. With inclusion of CRP in the model, the indirect effect of BMI on LTL through CRP was estimated at ß equal to -.023 (P < .001), and the direct effect of BMI on LTL in its absolute value decreased to ß equal to -.031 (P = .025). The mediation effect of CRP was estimated at 42.6%. The mediation model parameters did not differ significantly between race and sex groups. CONCLUSION: These results suggest that the inverse BMI-LTL association is partly mediated by obesity-induced inflammation. The significant direct effect of BMI on LTL with removal of the mediation effect through CRP indicates that obesity is associated with LTL attrition also through other noninflammatory mechanisms.

Intermediate Effects of Body Mass Index and C-Reactive Protein on the Serum Cotinine- Leukocyte Telomere Length Association.

We aimed to examine the association between serum cotinine and leukocyte telomere length (LTL) and the intermediate effects of body mass index (BMI) and C-reactive protein (CRP) on modulating the association. This study included 4,047 adults from the 1999 to 2002 National Health and Nutrition Examination Survey. In the combined sample, after adjusting for age, race, sex, physical activity, and alcohol use, the total effect of serum cotinine on LTL was significant (standardized regression coefficient, ß = -0.049, p = 0.001) without BMI and CRP included in the model. With inclusion of BMI but without CRP in the model, the direct effect of cotinine on LTL in its absolute value increased to ß = -0.053 (p < 0.001), and the suppression effect of BMI was estimated at 8.8%. With inclusion of CRP but without BMI in the model, the direct effect of cotinine on LTL in its absolute value decreased to ß = -0.040 (p = 0.008), and the mediation effect of CRP was estimated at 16.9%. With inclusion of both BMI and CRP in the model, BMI and CRP still had significant suppression and mediation effects, respectively, on the cotinine-LTL association. These findings suggest that weight and inflammation have different roles in the inverse association between serum cotinine and LTL.