Cross-species Association Between Telomere Length and Glucocorticoid Exposure
| Autor: | Susan M. Webb, Alicia Santos, Anna Aulinas, Mary E. McCaul, Richard S. Lee, Gary S. Wand, Eugenia Resmini, Jenny L. Carey, Peter P. Zandi |
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| Rok vydání: | 2021 |
| Předmět: |
Male
Aging Endocrinology Diabetes and Metabolism Clinical Biochemistry Biochemistry Rats Sprague-Dawley stress Mice chemistry.chemical_compound Cushing syndrome Endocrinology Corticosterone telomere length Chronic stress Cushing Syndrome Telomere Shortening glucocorticoids Middle Aged cellular aging Female allostatic load Glucocorticoid medicine.drug Adult medicine.medical_specialty Context (language use) cortisol Bedtime Species Specificity Stress Physiological Internal medicine medicine Animals Humans Online Only Articles Glucocorticoids business.industry Dentate gyrus Biochemistry (medical) medicine.disease Rats Telomere Mice Inbred C57BL Disease Models Animal chemistry Case-Control Studies business Follow-Up Studies |
| Zdroj: | J Clin Endocrinol Metab JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau instname |
| ISSN: | 1945-7197 0021-972X |
| DOI: | 10.1210/clinem/dgab519 |
| Popis: | ContextChronic exposure to glucocorticoids (GCs) or stress increases the risk of medical disorders, including cardiovascular and neuropsychiatric disorders. GCs contribute to accelerated aging; however, while the link between chronic GC exposure and disease onset is well established, the underpinning mechanisms are not clear.ObjectiveWe explored the potential nexus between GCs or stress exposure and telomere length.MethodsIn addition to rats exposed to 3 weeks of chronic stress, an iatrogenic mouse model of Cushing syndrome (CS), and a mouse neuronal cell line, we studied 32 patients with CS and age-matched controls and another cohort of 75 healthy humans.Results(1) Exposure to stress in rats was associated with a 54.5% (P = 0.036) reduction in telomere length in T cells. Genomic DNA (gDNA) extracted from the dentate gyrus of stressed and unstressed rats showed 43.2% reduction in telomere length (P = 0.006). (2) Mice exposed to corticosterone had a 61.4% reduction in telomere length in blood gDNA (P = 5.75 × 10-5) and 58.8% reduction in telomere length in the dentate gyrus (P = 0.002). (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, which was not different from that of healthy controls (P = 0.08). For both cured and active CS, telomere length correlated significantly with duration of hypercortisolism (R2 = 0.22, P = 0.007). (4) There was a 27.6% reduction in telomere length between low and high tertiles in bedtime cortisol levels of healthy participants (P = 0.019).ConclusionOur findings demonstrate that exposure to stress and/or GCs is associated with shortened telomeres, which may be partially reversible. |
| Databáze: | OpenAIRE |
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