Downregulation of transposable elements extends lifespan in Caenorhabditis elegans

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...

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Veröffentlicht in:Nature communications 2023-08, Vol.14 (1), p.5278-18, Article 5278
Hauptverfasser: Sturm, Ádám, Saskői, Éva, Hotzi, Bernadette, Tarnóci, Anna, Barna, János, Bodnár, Ferenc, Sharma, Himani, Kovács, Tibor, Ari, Eszter, Weinhardt, Nóra, Kerepesi, Csaba, Perczel, András, Ivics, Zoltán, Vellai, Tibor
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Sprache:eng
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Zusammenfassung: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 N 6 -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 N 6 -adenine methylation plays a pivotal role in ageing control. Transposable elements in somatic cells become increasingly mobile during ageing. Here, the authors show that in the nematode Caenorhabditis elegans , downregulation of transposable elements extends lifespan, and that their increases with age are coupled with progressively growing N 6 -adenine methylation in these genetic loci.
ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-023-40957-9