Abstract：
Various biological attributes associated with individual fitness in animals change predictably over the lifespan of an organism. Therefore, the study of animal ecology and the work of conservationists frequently relies upon the ability to assign animals to functionally relevant age classes to model population fitness. Several approaches have been applied to determining individual age and, while these methods have proved useful, they are not without limitations and often lack standardisation or are only applicable to specific species. For these reasons, scientists have explored the potential use of biological clocks towards creating a universal age-determination method. Two biological clocks, tooth layer annulation and otolith layering have found universal appeal. Both methods are highly invasive and most appropriate for post-mortem age-at-death estimation. More recently, attributes of cellular ageing previously explored in humans have been adapted to studying ageing in animals for the use of less-invasive molecular methods for determining age. Here, we review two such methods, assessment of methylation and telomere length, describing (i) what they are, (ii) how they change with age, and providing (iii) a summary and meta-analysis of studies that have explored their utility in animal age determination. We found that both attributes have been studied across multiple vertebrate classes, however, telomere studies were used before methylation studies and telomere length has been modelled in nearly twice as many studies. Telomere length studies included in the review often related changes to stress responses and illustrated that telomere length is sensitive to environmental and social stressors and, in the absence of repair mechanisms such as telomerase or alternative lengthening modes, lacks the ability to recover. Methylation studies, however, while also detecting sensitivity to stressors and toxins, illustrated the ability to recover from such stresses after a period of accelerated ageing, likely due to constitutive expression or reactivation of repair enzymes such as DNA methyl transferases. We also found that both studied attributes have parentally heritable features, but the mode of inheritance differs among taxa and may relate to heterogamy. Our meta-analysis included more than 40 species in common for methylation and telomere length, although both analyses included at least 60 age-estimation models. We found that methylation outperforms telomere length in terms of predictive power evidenced from effect sizes (more than double that observed for telomeres) and smaller prediction intervals. Both methods produced age correlation models using similar sample sizes and were able to classify individuals into young, middle, or old age classes with high accuracy. Our review and meta-analysis illustrate that both methods are well suited to studying age in animals and do not suffer significantly from variation due to differences in the lifespan of the species, genome size, karyotype, or tissue type but rather that quantitative method, patterns of inheritance, and environmental factors should be the main considerations. Thus, provided that complex factors affecting the measured trait can be accounted for, both methylation and telomere length are promising targets to develop as biomarkers for age determination in animals.
摘要：
与动物个体适应性相关的各种生物学属性在生物体的寿命期间可预测地变化。因此,动物生态学的研究和保护主义者的工作通常依赖于将动物分配到功能相关的年龄类别以模拟种群适应性的能力。已经应用了几种方法来确定个人年龄，虽然这些方法被证明是有用的，它们并非没有限制，通常缺乏标准化或仅适用于特定物种。由于这些原因,科学家们已经探索了生物钟的潜在用途，以创建一种通用的年龄确定方法。两个生物钟,牙层环合和耳石分层已发现普遍的吸引力。这两种方法都是高度侵入性的，最适合死后死亡年龄估计。最近,先前在人类中探索的细胞衰老的属性已适用于研究动物的衰老，以使用侵入性较小的分子方法来确定年龄。这里,我们回顾了两种这样的方法，甲基化和端粒长度的评估，描述（i）它们是什么，(ii)它们如何随着年龄而变化，并提供（iii）对探索其在动物年龄确定中的效用的研究的摘要和荟萃分析。我们发现这两个属性已经在多个脊椎动物类别中进行了研究，然而,端粒研究在甲基化研究之前使用，端粒长度在几乎两倍的研究中被建模。综述中包括的端粒长度研究通常与应激反应的变化有关，并说明端粒长度对环境和社会压力敏感，在缺乏端粒酶或其他延长模式等修复机制的情况下，缺乏恢复的能力。甲基化研究，然而,同时还检测对应激源和毒素的敏感性，说明了在加速老化一段时间后从这种应力中恢复的能力，可能是由于DNA甲基转移酶等修复酶的组成型表达或再激活。我们还发现，这两个研究的属性都具有亲本遗传特征，但是不同分类群的遗传方式不同，可能与异性恋有关。我们的荟萃分析包括超过40种常见的甲基化和端粒长度，尽管两项分析都包括至少60个年龄估计模型.我们发现，甲基化在预测能力方面优于端粒长度，从效应大小（端粒观察到的两倍以上）和较小的预测间隔证明。两种方法都使用相似的样本量产生了年龄相关模型，并且能够将个体分类为年轻，中间,或具有高精度的老年课程。我们的审查和荟萃分析表明，这两种方法都非常适合研究动物的年龄，并且由于物种寿命的差异而不会显着变化，基因组大小，核型,或组织类型，而是定量方法，继承模式，环境因素应该是主要考虑因素。因此，前提是可以考虑影响测量性状的复杂因素，甲基化和端粒长度都是有希望的靶标，可作为动物年龄确定的生物标志物。
