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皮质醇觉醒反应对端粒长度的影响:男性和女性的趋势。

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

机构信息

Monash Alfred Psychiatry Research Centre, Monash University and the Alfred Hospital, Melbourne, Vic, Australia.

Department of Saude Mental, Faculdade de Medicina, UFMG, Belo Horizonte, Brazil.

出版信息

Eur J Neurosci. 2022 May;55(9-10):2794-2803. doi: 10.1111/ejn.14996. Epub 2021 Jan 5.

Abstract

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.

摘要

虽然端粒磨损与正常衰老过程有关,但端粒长度(TL)较短与急性和慢性应激源有关。一种假设的神经生物学因素是皮质醇应激反应的失调,它会导致 DNA 损伤,从而影响 DNA 端粒帽。皮质醇应激反应和端粒动力学都存在明显的性别差异,但关于皮质醇与 TL 之间关系的性别特异性尚无明确的研究。本研究使用数学方程模型,在健康人群中描述了性别对皮质醇水平和端粒长度之间关系的影响。通过 ELISA 方法测量了 51 名健康参与者(28 名男性,23 名女性)的皮质醇觉醒反应(CAR)。qPCR 从唾液中提取的基因组 DNA 中确定了 TL。为了评估游离皮质醇对相对 TL 比的影响,对两个变量的半对数回归图进行了拟合,趋势与性别有关,使用样条曲线。结果表明,CAR 和 TL 关联的关系在男性和女性之间存在显著差异(p=0.03)。这些结果表明,这种关系不是线性的,可以用复杂的反正弦函数来表示,而且这种模式在男性和女性中是相反的。男性表现出正相关,CAR 水平较高与端粒序列较长有关。女性表现出负相关。未来的研究必须在研究端粒长度时,仔细考虑性别和整个生命周期中的性激素等调节因素。

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