Groningen Institute for Evolutionary Life Sciences, University of Groningen, Groningen, The Netherlands.
Faculty of Biological Sciences, School of Biology, University of Leeds, Leeds, UK.
Mol Ecol. 2023 Sep;32(17):4725-4741. doi: 10.1111/mec.17065. Epub 2023 Jul 3.
Inferring the chronological and biological age of individuals is fundamental to population ecology and our understanding of ageing itself, its evolution, and the biological processes that affect or even cause ageing. Epigenetic clocks based on DNA methylation (DNAm) at specific CpG sites show a strong correlation with chronological age in humans, and discrepancies between inferred and actual chronological age predict morbidity and mortality. Recently, a growing number of epigenetic clocks have been developed in non-model animals and we here review these studies. We also conduct a meta-analysis to assess the effects of different aspects of experimental protocol on the performance of epigenetic clocks for non-model animals. Two measures of performance are usually reported, the R of the association between the predicted and chronological age, and the mean/median absolute deviation (MAD) of estimated age from chronological age, and we argue that only the MAD reflects accuracy. R for epigenetic clocks based on the HorvathMammalMethylChip4 was higher and the MAD scaled to age range lower, compared with other DNAm quantification approaches. Scaled MAD tended to be lower among individuals in captive populations, and decreased with an increasing number of CpG sites. We conclude that epigenetic clocks can predict chronological age with relatively high accuracy, suggesting great potential in ecological epigenetics. We discuss general aspects of epigenetic clocks in the hope of stimulating further DNAm-based research on ageing, and perhaps more importantly, other key traits.
推断个体的年龄是人口生态学和我们对衰老本身、衰老的进化以及影响甚至导致衰老的生物学过程的理解的基础。基于特定 CpG 位点的 DNA 甲基化（DNAm）的表观遗传钟在人类中与实际年龄具有很强的相关性，并且推断的与实际的年龄之间的差异预测发病率和死亡率。最近，越来越多的非模型动物的表观遗传钟已经被开发出来，我们在这里对这些研究进行了综述。我们还进行了荟萃分析，以评估实验方案的不同方面对非模型动物表观遗传钟性能的影响。通常报告两种性能指标，即预测年龄与实际年龄之间的相关性的 R 值，以及估计年龄与实际年龄的平均/中位数绝对偏差（MAD），我们认为只有 MAD 反映了准确性。基于 HorvathMammalMethylChip4 的表观遗传钟的 R 值更高，且年龄范围的 MAD 标准化值更低，与其他 DNAm 定量方法相比。在圈养种群中的个体中，标准化 MAD 往往较低，并且随着 CpG 位点数量的增加而降低。我们得出结论，表观遗传钟可以以相对较高的准确性预测实际年龄，这表明其在生态表观遗传学中具有巨大的潜力。我们讨论了表观遗传钟的一般方面，希望能激发更多基于 DNAm 的衰老研究，也许更重要的是，其他关键特征的研究。
