Armstrong Emma, Boonekamp Jelle
School of Biodiversity, One Health & Veterinary Medicine, University of Glasgow, Glasgow, United Kingdom; The Roslin Institute, The University of Edinburgh, Easter Bush Campus, Midlothian, United Kingdom.
School of Biodiversity, One Health & Veterinary Medicine, University of Glasgow, Glasgow, United Kingdom.
Ageing Res Rev. 2023 Mar;85:101854. doi: 10.1016/j.arr.2023.101854. Epub 2023 Jan 16.
Telomere attrition is considered a hallmark of ageing. Untangling the proximate causes of telomere attrition may therefore reveal important aspects about the ageing process. In a landmark paper in 2002 Thomas von Zglinicki demonstrated that oxidative stress accelerates telomere attrition in cell culture. In the next 20 years, oxidative stress became firmly embedded into modern theories of ageing and telomere attrition. However, a recent surge of in vivo studies reveals an inconsistent pattern questioning the unequivocal role of oxidative stress in telomere length and telomere attrition (henceforth referred to as telomere dynamics), in living organisms. Here we report the results of the first formal meta-analysis on the association between oxidative stress and telomere dynamics in vivo, representing 37 studies, 4969 individuals, and 18,677 correlational measurements. The overall correlation between oxidative stress markers and telomere dynamics was indistinguishable from zero (r = 0.027). This result was independent of the type of oxidative stress marker, telomere dynamic, or taxonomic group. However, telomere measurement method affected the analysis and the subset of TRF-based studies showed a significant overall correlation (r = 0.09), supporting the prediction that oxidative stress accelerates telomere attrition. The correlation was more pronounced in short-lived species and during the adult life phase, when ageing becomes apparent. We then performed an additional meta-analysis of interventional studies (n = 7) manipulating oxidative stress. This revealed a significant effect of treatment on telomere dynamics (d=0.36). Our findings provide new support for the hypothesis that oxidative stress causes telomere attrition in living organisms.
端粒损耗被认为是衰老的一个标志。因此，厘清端粒损耗的直接原因可能会揭示衰老过程的重要方面。在2002年的一篇具有里程碑意义的论文中，托马斯·冯·兹格林斯基证明氧化应激会加速细胞培养中的端粒损耗。在接下来的20年里，氧化应激牢固地融入了现代衰老理论和端粒损耗理论。然而，最近大量的体内研究揭示了一种不一致的模式，对氧化应激在活生物体中端粒长度和端粒损耗（以下简称端粒动态）中的明确作用提出了质疑。在此，我们报告了第一项关于体内氧化应激与端粒动态之间关联的正式荟萃分析结果，该分析涵盖了37项研究、4969名个体以及18677次相关性测量。氧化应激标志物与端粒动态之间的总体相关性与零无显著差异（r = 0.027）。这一结果与氧化应激标志物的类型、端粒动态或分类学类别无关。然而，端粒测量方法影响了分析，基于端粒重复序列长度（TRF）的研究子集显示出显著的总体相关性（r = 0.09），支持了氧化应激会加速端粒损耗的预测。这种相关性在短命物种以及衰老变得明显的成年生命阶段更为显著。然后，我们对操纵氧化应激的干预性研究（n = 7）进行了另一项荟萃分析。这揭示了治疗对端粒动态有显著影响（d = 0.36）。我们的研究结果为氧化应激导致活生物体中端粒损耗这一假说提供了新的支持。
