Influence of cortisol awakening response on telomere length: Trends for males and females

• Published in: The European journal of neuroscience 2022-05, Vol.55 (9-10), p.2794-2803
• Main Authors: Thomas, Natalie, Hudaib, Abdul‐Rahman, Romano‐Silva, Marco, Bozaoglu, Kiymet, H. X. Thomas, Elizabeth, Rossell, Susan, Kulkarni, Jayashri, Gurvich, Caroline
• Format: Article
• Language: English
• Subjects: Aging; Cortisol; Deoxyribonucleic acid; DNA; DNA damage; Females; Hormones; Life span; Males; Mathematical models; Saliva; salivary telomere length; Sex differences; Sex hormones; stress; Stress response; Telomeres
• ISSN: 0953-816X; 1460-9568
• DOI: 10.1111/ejn.14996

Although telomere attrition is associated with the process of normal ageing, shorter telomere length (TL) has been associated with acute and chronic stressors. A neurobiological factor hypothesised to be responsible for this accelerated attrition is the dysregulation of the cortisol stress response, which can induce DNA damage affecting DNA telomeric caps. Marked sex differences are reported in both the cortisol stress response and telomere dynamics, yet no explicit investigation of sex specificity on the relationship between cortisol and TL exists. This study used mathematical equation modelling to describe the relationship between diurnal cortisol levels and telomere length within the context of sex, in a healthy population. Cortisol awakening responses (CAR) were measured via ELISA methodology in fifty‐one healthy participants (28 males, 23 females). qPCRs determined TL from genomic DNA extracted from saliva. To assess the effect of free cortisol on relative TL ratio, a semi‐log regression plot of the two variables trended for sex were fitted using spline curves. Results demonstrated significant differences between males and females in the relationship defining CAR and TL association (p = 0.03). These results suggest the relationship is not linear and can be represented as a complex arcsin function, and that the patterns are opposite in males and females. Males demonstrate a positive correlation, with higher levels of CAR being associated with longer telomere sequences. Females demonstrated a negative correlation. Future studies must carefully take into consideration moderating factors such as sex, and sex hormones across the lifespan when investigating telomere length. Prediction plot depicting the mathematical relationship between telomere length (log) and cortisol awakening response (CAR) as area under the curve (Area), trended for sex (male, female). Results suggest the relationship is not linear and can be represented as a complex arcsin or inverse sine function and these patterns are observed to be opposing in males and females.