Association between Urinary Excretion of Cortisol and Markers of Oxidatively Damaged DNA and RNA in Humans

Anders Joergensen,Luigi Ferrucci,Richard D Semba,Henrik E Poulsen,Kasper Broedbaek,Allan Weimann,Martin B Joergensen,Consuelo Borras

doi:10.1371/journal.pone.0020795

Abstract

Chronic psychological stress is associated with accelerated aging, but the underlying biological mechanisms are not known. Prolonged elevations of the stress hormone cortisol is suspected to play a critical role. Through its actions, cortisol may potentially induce oxidatively generated damage to cellular constituents such as DNA and RNA, a phenomenon which has been implicated in aging processes. We investigated the relationship between 24 h excretion of urinary cortisol and markers of oxidatively generated DNA and RNA damage, 8-oxo-7,8-dihydro-2′-deoxyguanosine and 8-oxo-7,8-dihydroguanosine, in a sample of 220 elderly men and women (age 65 – 83 years). We found a robust association between the excretion of cortisol and the oxidation markers (R2 = 0.15, P<0.001 for both markers). Individuals in the highest quartile of cortisol excretion had a 57% and 61% higher median excretion of the DNA and RNA oxidation marker, respectively, than individuals in the lowest quartile. The finding adds support to the hypothesis that cortisol-induced damage to DNA/RNA is an explanatory factor in the complex relation between stress, aging and disease.

Highlights

Modern biomedical research has shed light on the popular notion that psychological stress has a negative influence on health and accelerates aging
Where the acute cortisol response to stress is necessary for survival, psychological stress associated with prolonged hypercortisolism supposedly leads to a state of stable dysregulation that is detrimental to health over time [1]
Linear regression analysis showed significant positive relationships between both 8-oxodG and 8-oxoGuo and cortisol excretion (R2 = 0.15, P,0.001 for both markers) (Figure 1A). This result persisted after the adjustment for multiple known or possible confounders of oxidative stress in multivariate analysis, in which only serum ferritin and cortisol were significantly associated with the oxidation markers (Table 2)

Summary

Introduction

Modern biomedical research has shed light on the popular notion that psychological stress has a negative influence on health and accelerates aging. Prolonged stress is thought to induce a ‘‘wear and tear’’ syndrome, in which a range of compensatory physiological mechanisms as well as behavioural changes leads to negative health influences [1]. The central link between prolonged psychological stress, aging, and disease, is suspected to be chronic elevations of cortisol and other stress hormones. Where the acute cortisol response to stress is necessary for survival, psychological stress associated with prolonged hypercortisolism supposedly leads to a state of stable dysregulation that is detrimental to health over time [1]. One possibility is that the combined effects of cortisol lead to increased oxidative stress, in which the mitochondrial production of reactive oxygen species (ROS) exceeds the antioxidant potential, thereby causing damage to other molecules such as lipids, proteins and DNA/RNA. In particular the oxidatively generated damage to DNA, has been suggested to be a central mediator of aging [7,8]

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Conclusion