Cross-species Association Between Telomere Length and Glucocorticoid Exposure
Por:
Lee, RS, Zandi, PP, Santos, A, Aulinas, A, Carey, JL, Webb, SM, McCaul, ME, Resmini, E, Wand, GS
Publicada:
1 dic 2021
Ahead of Print:
1 jul 2021
Resumen:
Context: Chronic 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.
Objective: We explored the potential nexus between GCs or stress exposure and telomere length.
Methods: In 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 x 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 (R-2 = 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).
Conclusion: Our findings demonstrate that exposure to stress and/or GCs is associated with shortened telomeres, which may be partially reversible.
Filiaciones:
Lee, RS:
Johns Hopkins Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA
Zandi, PP:
Johns Hopkins Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA
Johns Hopkins Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD 21205 USA
Santos, A:
Hosp Santa Creu & Sant Pau, Ctr Invest Biomed Red Enfermedades Raras CIBER ER, Endocrinol Med Dept, Unit747,ISCIII,IIB St Pau, Barcelona, Spain
Univ Autonoma Barcelona UAB, Barcelona, Spain
Aulinas, A:
Hosp Santa Creu & Sant Pau, Ctr Invest Biomed Red Enfermedades Raras CIBER ER, Endocrinol Med Dept, Unit747,ISCIII,IIB St Pau, Barcelona, Spain
Univ Autonoma Barcelona UAB, Barcelona, Spain
Carey, JL:
Johns Hopkins Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA
Webb, SM:
Hosp Santa Creu & Sant Pau, Ctr Invest Biomed Red Enfermedades Raras CIBER ER, Endocrinol Med Dept, Unit747,ISCIII,IIB St Pau, Barcelona, Spain
Univ Autonoma Barcelona UAB, Barcelona, Spain
McCaul, ME:
Johns Hopkins Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA
Resmini, E:
Hosp Santa Creu & Sant Pau, Ctr Invest Biomed Red Enfermedades Raras CIBER ER, Endocrinol Med Dept, Unit747,ISCIII,IIB St Pau, Barcelona, Spain
Univ Autonoma Barcelona UAB, Barcelona, Spain
Wand, GS:
Johns Hopkins Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA
Johns Hopkins Sch Med, Dept Med, Baltimore, MD 21205 USA
hybrid, Green Published
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