The Longitudinal Relationship Between Cortisol Responses to Mental Stress and Leukocyte Telomere Attrition

Context Chronic psychological stress has been associated with shorter telomeres, but the underlying mechanisms are poorly understood. One possibility is that the neuroendocrine responses to stress exposure are involved. Objective To test the hypothesis that greater cortisol responsivity to acute stressors predicts more rapid telomere attrition. Design We measured salivary cortisol responses to 2 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 to 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 nonresponders (n = 255) using a criterion (≥20% increase in cortisol concentration) 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 nonresponders on follow-up, after controlling statistically for age, sex, socioeconomic status, smoking, time of day of stress , 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 nonresponders 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.