Downregulation of transposable elements extends lifespan in Caenorhabditis elegans

Ádám Sturm, Éva Saskői, Bernadette Hotzi, Anna Tarnóci, János Barna, Ferenc Bodnár, Himani Sharma, Tibor Kovács, Eszter Ari, Nóra Weinhardt, Csaba Kerepesi, András Perczel, Zoltán Ivics and Tibor Vellai ()
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Ádám Sturm: Eötvös Loránd University (ELTE)
Éva Saskői: Eötvös Loránd University (ELTE)
Bernadette Hotzi: Eötvös Loránd University (ELTE)
Anna Tarnóci: Eötvös Loránd Research Network (ELKH)-ELTE Genetics Research Group
János Barna: Eötvös Loránd Research Network (ELKH)-ELTE Genetics Research Group
Ferenc Bodnár: Eötvös Loránd University (ELTE)
Himani Sharma: Eötvös Loránd University (ELTE)
Tibor Kovács: Eötvös Loránd University (ELTE)
Eszter Ari: Eötvös Loránd University (ELTE)
Nóra Weinhardt: Eötvös Loránd University (ELTE)
Csaba Kerepesi: Institute for Computer Science and Control (SZTAKI)
András Perczel: Eötvös Loránd University
Zoltán Ivics: Paul Ehrlich Institute
Tibor Vellai: Eötvös Loránd University (ELTE)

Nature Communications, 2023, vol. 14, issue 1, 1-18

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-40957-9

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