Cross-species Association Between Telomere Length and Glucocorticoid Exposure.
J Clin Endocrinol Metab
; 106(12): e5124-e5135, 2021 11 19.
Article
em En
| MEDLINE
| ID: mdl-34265046
ABSTRACT
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% (Pâ =â 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 (Pâ =â 0.006). (2) Mice exposed to corticosterone had a 61.4% reduction in telomere length in blood gDNA (Pâ =â 5.75â ×â 10-5) and 58.8% reduction in telomere length in the dentate gyrus (Pâ = 0.002). (3) We observed a 40.8% reduction in the telomere length in patients with active CS compared to healthy controls (Pâ =â 0.006). There was a 17.8% reduction in telomere length in cured CS patients, which was not different from that of healthy controls (Pâ =â 0.08). For both cured and active CS, telomere length correlated significantly with duration of hypercortisolism (R2â =â 0.22, Pâ =â 0.007). (4) There was a 27.6% reduction in telomere length between low and high tertiles in bedtime cortisol levels of healthy participants (Pâ =â 0.019).CONCLUSION:
Our findings demonstrate that exposure to stress and/or GCs is associated with shortened telomeres, which may be partially reversible.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Estresse Fisiológico
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Envelhecimento
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Síndrome de Cushing
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Modelos Animais de Doenças
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Encurtamento do Telômero
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Glucocorticoides
Tipo de estudo:
Etiology_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Adult
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Animals
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
J Clin Endocrinol Metab
Ano de publicação:
2021
Tipo de documento:
Article