Cross-species Association Between Telomere Length and Glucocorticoid Exposure.

Context Chronic exposure to glucocorticoids (GCs) or stress increases the risk of medical disorders, including cardiovascular and neuropsychiatric disorders. GCs contribute to an accelerated aging, while the link between chronic GCs exposure and disease onset is well established, the underpinning mechanisms are not clear. Objective we explored the potential nexus between GCs or stress exposure and telomere length. Design, setting, and participants rats exposed to three weeks of chronic stress; an iatrogenic mouse model of Cushing's syndrome (CS); a mouse neuronal cell line; 33 patients with CS and 75 healthy human people were studied. Results 1.Telomere length is associated with exposure to stress in rats: 54.5% (P=0.036) reduction in telomere length in the stressed animals. Genomic DNA extracted from the dentate gyrus of stressed and unstressed rats showed 43.2% reduction in telomere length (P=0.006). 2. Mice were exposed to corticosterone (CORT), this treatment produced a 61.4% reduction in telomere length in the blood gDNA (P=5.75x 10-5). 3. We observed a 40.8% reduction in the telomere length in patients with active CS compared to healthy controls (P=0.006). There was a 17.8% reduction in telomere length in cured CS patients, no different from controls (P=0.08). For both cured and active CS, telomere length correlated significantly with the duration of hypercortisolism (R2=0.22, P=0.007). 4. There was a 27.6% reduction in telomere length between low vs. high tertiles in bedtime cortisol levels (P=0.019). Conclusions Our findings demonstrate that exposure to stress and/or glucocorticoids is associated with shortened telomeres, and that shortening may be partially reversible.