BACKGROUND:The investigation evaluated the relationship between caffeine intake and coffee consumption and leukocyte telomere length, a biomarker of the senescence of cells. METHODS:A total of 5826 adults from the National Health and Nutrition Examination Survey (NHANES) were studied cross-sectionally. Using the quantitative polymerase chain reaction method, telomere length was compared to standard reference DNA. Caffeine intake from foods and beverages and coffee consumption were measured using a validated, multi-pass, computer-assisted, 24-h recall system administered by NHANES interviewers. The following covariates were controlled: age, gender, race, marital status, education, housing, smoking, BMI, physical activity, alcohol use, and coffee intake (or caffeine consumption). RESULTS:Caffeine consumption was inversely related to telomere length (F = 15.1, P = 0.0005). For each 100 mg of caffeine consumed, telomeres were 35.4 base pairs shorter, after adjusting for the covariates. For each 100 mg of caffeine consumed among coffee drinkers only, telomeres were 36.7 base pairs shorter (F = 9.0, P = 0.0054), and among non-coffee drinkers only, 40.0 base pairs shorter (F = 8.5, P = 0.0067). Conversely, coffee intake was positively related to telomere length (F = 12.6, P = 0.0013), independent of the covariates. CONCLUSIONS:Results suggest that caffeine consumption accounts for shorter telomeres in U.S. adults, independent of numerous covariates, whereas coffee intake predicts longer telomeres.