Decline in telomere length with increasing age across non‐human vertebrates: a meta‐analysis

The prediction that telomere length (TL) shortens with increasing age is a major element in considering the role of telomeres as a key player in evolution. While telomere attrition is found in humans both in vitro and in vivo, the increasing number of studies reporting diverse age-specific patterns of TL challenges the hypothesis of a universal decline of TL with increasing age. Here we performed a meta-analysis to estimate the relationship between TL and age across 175 estimates encompassing 98 species of vertebrates. We found that, on average, TL does decline with increasing age during adulthood. However, this decline was weak and variable across vertebrate classes, and we also found evidence for a publication bias that might weaken our current evidence of decreasing TL with increasing age. We found no evidence for a faster decline in TL with increasing age when considering the juvenile stage (from birth to age at first reproduction) compared to the adult stage. Heterogeneity in TL ageing rates was explained by the method used to measure telomeres: detectable TL declines with increasing age were found only among studies using TRF with in-gel hybridisation and qFISH methods, but not in studies using qPCR and Southern blot-based TRF methods. While we confirmed that TL declines with increasing age in most adult vertebrates, our results identify an influence of telomere measurement methodology, which highlights the need to examine more thoroughly the effect of the method of measurement on TL estimates.

端粒长度（telomere length, TL）随年龄增长而缩短这一假说，是将端粒视为演化关键参与者的核心考量要素之一。尽管已在人类的体外（in vitro）和体内（in vivo）环境中均观测到端粒损耗现象，但越来越多研究报道了TL呈现多样化的年龄特异性模式，这对"TL随年龄增长普遍缩短"这一假说提出了挑战。本研究开展了一项荟萃分析（meta-analysis），对涵盖98种脊椎动物（vertebrates）的175项TL测量估计值进行分析，以估算TL与年龄之间的关联。研究结果显示，成年阶段的TL平均而言确实随年龄增长而缩短。不过，这种缩短效应较为微弱，且在不同脊椎动物类群间存在差异；同时，本研究还发现了发表偏倚的证据，这可能会削弱我们当前关于TL随年龄增长而缩短的结论可信度。相较于成年阶段，在考虑幼体阶段（从出生至首次繁殖年龄）时，本研究未发现TL随年龄增长出现更快缩短的证据。TL衰老速率的异质性可通过端粒测量方法予以解释：仅在采用结合凝胶内杂交（in-gel hybridisation）的端粒限制性片段（telomere restriction fragment, TRF）技术以及定量荧光原位杂交（quantitative fluorescence in situ hybridization, qFISH）方法的研究中，观测到了可检测的TL随年龄增长而缩短的现象；而采用定量聚合酶链反应（quantitative polymerase chain reaction, qPCR）和基于Southern印迹法（Southern blot）的TRF方法的研究则未发现此类现象。尽管本研究证实了多数成年脊椎动物的TL会随年龄增长而缩短，但研究结果也凸显了端粒测量方法的影响，这表明我们需要更深入地探究测量方法对TL估算结果的影响。