Suppression of Transposable Element Activity Extends Life in Nematode Worms

There is a growing interest in the role of transposable elements in aging. These are sections of the genome, remnants of ancient viral infections, that are capable of copying themselves when active, causing mutational damage in the process. Transposable elements are suppressed in youth, their portions of the genome folded away and hidden from transcriptional machinery, but this suppression fails with age as epigenetic markers that determine the structure of the genome change. Any mechanism that increases mutational damage in large numbers of cells might be suspected to contribute to degenerative aging, but definitive proof is always a challenge, given the difficulty of adjusting just one feature of cellular biochemistry in isolation of all other features. Nonetheless, researchers make the attempt here in nematode worms, and the results are interesting.

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 somatic cells 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.

Link: https://doi.org/10.1038/s41467-023-40957-9

Comments

Hope its possible to take it out of genomes of future embryos.

Posted by: ciclo at September 8th, 2023 10:50 AM

Getting them out of the genomes of people who are already alive would be pretty nice too.

Posted by: Arcanyn at September 9th, 2023 6:52 AM
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