Department of Integrative Biology, University of California, Berkeley, CA, United States of America.
Department of Biological Sciences, San Jose State University, San Jose, CA, United States of America.
PLoS One. 2021 Oct 1;16(10):e0257370. doi: 10.1371/journal.pone.0257370. eCollection 2021.
The neuroendocrine stress response allows vertebrates to cope with stressors via the activation of the Hypothalamic-Pituitary-Adrenal (HPA) axis, which ultimately results in the secretion of glucocorticoids (GCs). Glucocorticoids have pleiotropic effects on behavior and physiology, and might influence telomere length dynamics. During a stress event, GCs mobilize energy towards survival mechanisms rather than to telomere maintenance. Additionally, reactive oxygen species produced in response to increased GC levels can damage telomeres, also leading to telomere shortening. In our systematic review and meta-analysis, we tested whether GC levels impact telomere length and if this relationship differs among time frame, life history stage, or stressor type. We hypothesized that elevated GC levels are linked to a decrease in telomere length.
We conducted a literature search for studies investigating the relationship between telomere length and GCs in non-human vertebrates using four search engines: Web of Science, Google Scholar, Pubmed and Scopus, last searched on September 27th, 2020. This review identified 31 studies examining the relationship between GCs and telomere length. We pooled the data using Fisher's Z for 15 of these studies. All quantitative studies underwent a risk of bias assessment. This systematic review study was registered in the Open Science Framework Registry (https://osf.io/rqve6).
The pooled effect size from fifteen studies and 1066 study organisms shows no relationship between GCs and telomere length (Fisher's Z = 0.1042, 95% CI = 0.0235; 0.1836). Our meta-analysis synthesizes results from 15 different taxa from the mammalian, avian, amphibian groups. While these results support some previous findings, other studies have found a direct relationship between GCs and telomere dynamics, suggesting underlying mechanisms or concepts that were not taken into account in our analysis. The risk of bias assessment revealed an overall low risk of bias with occasional instances of bias from missing outcome data or bias in the reported result.
We highlight the need for more targeted experiments to understand how conditions, such as experimental timeframes, stressor(s), and stressor magnitudes can drive a relationship between the neuroendocrine stress response and telomere length.
神经内分泌应激反应使脊椎动物能够通过激活下丘脑-垂体-肾上腺 (HPA) 轴来应对应激源,这最终导致糖皮质激素 (GCs) 的分泌。GCs 对行为和生理有多种影响,可能影响端粒长度动态。在应激事件中,GC 将能量转移到生存机制上,而不是维持端粒。此外,由于 GC 水平升高而产生的活性氧物质也会破坏端粒,导致端粒缩短。在我们的系统评价和荟萃分析中,我们测试了 GC 水平是否影响端粒长度,以及这种关系是否因时间框架、生活史阶段或应激源类型而异。我们假设升高的 GC 水平与端粒长度的缩短有关。
我们使用四个搜索引擎(Web of Science、Google Scholar、Pubmed 和 Scopus)对非人类脊椎动物中研究端粒长度与 GCs 之间关系的文献进行了检索:Web of Science、Google Scholar、Pubmed 和 Scopus,最后一次检索时间为 2020 年 9 月 27 日。该综述确定了 31 项研究,这些研究检查了 GCs 与端粒长度之间的关系。我们使用 Fisher 的 Z 对其中 15 项研究的数据进行了汇总。所有定量研究都进行了偏倚风险评估。这项系统评价研究在开放科学框架注册处进行了注册(https://osf.io/rqve6)。
15 项研究和 1066 个研究生物体的汇总效应大小表明,GCs 与端粒长度之间没有关系(Fisher 的 Z = 0.1042,95%CI = 0.0235;0.1836)。我们的荟萃分析综合了来自哺乳动物、鸟类和两栖动物组的 15 个不同分类群的结果。虽然这些结果支持了一些先前的发现,但其他研究发现 GCs 与端粒动力学之间存在直接关系,这表明我们的分析中没有考虑到潜在的机制或概念。偏倚风险评估显示,整体偏倚风险较低,但偶尔会出现缺失结果数据或报告结果的偏倚。
我们强调需要进行更有针对性的实验,以了解实验时间框架、应激源和应激源大小等条件如何导致神经内分泌应激反应与端粒长度之间的关系。