The longitudinal relationship between cortisol responses to mental stress and leukocyte telomere attrition

Context: Chronic psychological stress has been associated with shorter telomeres in some studies, but the underlying mechanisms are poorly understood. One possibility is that the neuroendocrine responses associated with stress exposure are involved. Objective: To testing the hypothesis that greater cortisol responsivity to acute stressors predicts more rapid telomere attrition. Design: We measured salivary cortisol responses to two challenging behavioral tasks. Leukocyte telomere length was measured at the time of mental stress testing and 3 years later. Participants: We studied 411 initially healthy men and women aged 54-76 years. Main outcome measure: Leukocyte telomere length. Results: Cortisol responses to this protocol were small, we divided participants into cortisol responders (n = 156) and non-responders (n = 255) using a criterion (≥20%) previously shown to predict increases in cardiovascular disease risk. There was no significant association between cortisol responsivity and baseline telomere length, although cortisol responders tended to have somewhat shorter telomeres (β = -0.061, standard error 0.049). But cortisol responders had shorter telomeres and more rapid telomere attrition than non-responders on follow-up, after controlling statistically for age, gender, socioeconomic status, smoking, time of day of stress testing and baseline telomere length (β = -0.10, standard error 0.046, p = 0.029). The association was maintained after additional control for cardiovascular risk factors (β = -0.11, p = 0.031). The difference between cortisol responders and non-responders was equivalent to approximately 2 years in aging. Conclusions: These findings suggest that cortisol responsivity may mediate in part the relationship between psychological stress and cellular aging.