Mobility of transposable elements (TEs) frequently leads to insertional mutations in functional DNA regions. In the potentially immortal germline, TEs are effectively suppressed by the Piwi-piRNA pathway. However, in the genomes of ageing somatic cells lacking the effects of the pathway, TEs become increasingly mobile during the adult lifespan, and their activity is associated with genomic instability. Whether the progressively increasing mobilization of TEs is a cause or a consequence of ageing remains a fundamental problem in biology. Here we show that in the nematode Caenorhabditis elegans, the downregulation of active TE families extends lifespan. Ectopic activation of Piwi proteins in the soma also promotes longevity. Furthermore, DNA N⁶-adenine methylation at TE stretches gradually rises with age, and this epigenetic modification elevates their transcription as the animal ages. These results indicate that TEs represent a novel genetic determinant of ageing, and that N⁶-adenine methylation plays a pivotal role in ageing control.

转座元件 (TE) 的移动性经常导致功能性 DNA 区域的插入突变。在潜在的永生种系中，TE 受到 Piwi-piRNA 途径的有效抑制。然而，在缺乏该途径影响的衰老体细胞的基因组中，TE 在成年生命周期中变得越来越移动，并且它们的活动与基因组不稳定相关。 TEs 动员的逐渐增加是衰老的原因还是结果仍然是生物学中的一个基本问题。在这里，我们表明，在线虫秀丽隐杆线虫中，活性 TE 家族的下调可以延长寿命。体细胞中 Piwi 蛋白的异位激活也能延长寿命。此外，TE 处的 DNA N ⁶ -腺嘌呤甲基化随着年龄的增长而逐渐升高，并且这种表观遗传修饰随着动物年龄的增长而提高了它们的转录。这些结果表明TE代表了一种新的衰老遗传决定因素，并且N ⁶ -腺嘌呤甲基化在衰老控制中发挥着关键作用。