Downregulation of transposable elements extends lifespan in Caenorhabditis elegans

Sturm, Ádám and Saskői, Éva and Hotzi, Bernadette and Tarnóci, Anna and Barna, János and Bodnár, Ferenc and Sharma, Himani and Kovács, Tibor and Ari, Eszter and Weinhardt, Nóra and Kerepesi, Csaba and Perczel, András and Ivics, Zoltán and Vellai, Tibor (2023) Downregulation of transposable elements extends lifespan in Caenorhabditis elegans. NATURE COMMUNICATIONS, 14 (1). ISSN 2041-1723

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Abstract

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.

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