Elevated epigenetic age in wild compared to lab-raised house mice

Elevated epigenetic age in wild compared to lab-raised house mice
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与实验室饲养的家鼠相比,野生小鼠的表观遗传年龄更高

DOI:
10.1101/2023.10.25.563913
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发表时间:
2023
期刊:
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影响因子:
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通讯作者:
Hanski E
Hanski E
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作者:
Hanski E

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年龄是种群生态学中的一个关键参数,随着生物体在早期生命中的发育和后期衰老,无数的生物过程会随着年龄的变化而变化。由于年龄通常难以用非致死方法准确测量,因此年龄估计的表观遗传方法(表观遗传时钟)已成为动物生态学中的流行工具,并且通常使用已知年龄的圈养动物进行开发或校准。然而,研究通常依赖于侵入性血液或组织样本,这限制了它们在更敏感或难以捉摸的物种中的应用。此外,很少有研究直接评估甲基化模式和表观遗传年龄估计值如何在环境背景下进行比较(例如圈养或实验室动物与野生动物)。在这里,我们使用来自非侵入性粪便样本的DNA,从实验室小鼠(品系C57 BL/6,小家鼠)中建立了一个有针对性的表观遗传时钟,然后用它来估计未知年龄的野生小鼠(小家鼠)种群的年龄。这个实验室小鼠衍生的表观遗传时钟准确地预测了成年野生小鼠的年龄大于青少年,并表明野生小鼠的表观遗传年龄通常会随着时间的推移而增加,但个体之间的表观遗传衰老率差异很大。我们的研究结果还表明,对于给定的体重,野生小鼠在靶向CpG位点上的甲基化程度高于实验室小鼠(结果是表观遗传年龄估计值始终较高),即使是最小的幼年小鼠。这表明野生小鼠和实验室小鼠可能从生命早期就表现出不同的CpG甲基化水平,并表明在实验室动物上开发表观遗传时钟并将其应用于野外时需要谨慎。
Age is a key parameter in population ecology, with a myriad of biological processes changing with age as organisms develop in early life then later senesce. As age is often hard to accurately measure with non‐lethal methods, epigenetic methods of age estimation (epigenetic clocks) have become a popular tool in animal ecology and are often developed or calibrated using captive animals of known age. However, studies typically rely on invasive blood or tissue samples, which limit their application in more sensitive or elusive species. Moreover, few studies have directly assessed how methylation patterns and epigenetic age estimates compare across environmental contexts (e.g. captive or laboratory‐based vs. wild animals). Here, we built a targeted epigenetic clock from laboratory house mice (strain C57BL/6,Mus musculus) using DNA from non‐invasive faecal samples, and then used it to estimate age in a population of wild mice (Mus musculus domesticus) of unknown age. This laboratory mouse‐derived epigenetic clock accurately predicted adult wild mice to be older than juveniles and showed that wild mice typically increased in epigenetic age over time, but with wide variation in epigenetic ageing rate among individuals. Our results also suggested that, for a given body mass, wild mice had higher methylation across targeted CpG sites than laboratory mice (and consistently higher epigenetic age estimates as a result), even among the smallest, juvenile mice. This suggests wild and laboratory mice may display different CpG methylation levels from very early in life and indicates caution is needed when developing epigenetic clocks on laboratory animals and applying them in the wild.