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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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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10465613/
https://www.ncbi.nlm.nih.gov/pubmed/37644049
http://dx.doi.org/10.1038/s41467-023-40957-9
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author 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
author_facet 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
author_sort Sturm, Ádám
collection PubMed
description 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.
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spelling pubmed-104656132023-08-31 Downregulation of transposable elements extends lifespan in Caenorhabditis elegans 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 Nat Commun Article 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. Nature Publishing Group UK 2023-08-29 /pmc/articles/PMC10465613/ /pubmed/37644049 http://dx.doi.org/10.1038/s41467-023-40957-9 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
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
Downregulation of transposable elements extends lifespan in Caenorhabditis elegans
title Downregulation of transposable elements extends lifespan in Caenorhabditis elegans
title_full Downregulation of transposable elements extends lifespan in Caenorhabditis elegans
title_fullStr Downregulation of transposable elements extends lifespan in Caenorhabditis elegans
title_full_unstemmed Downregulation of transposable elements extends lifespan in Caenorhabditis elegans
title_short Downregulation of transposable elements extends lifespan in Caenorhabditis elegans
title_sort downregulation of transposable elements extends lifespan in caenorhabditis elegans
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10465613/
https://www.ncbi.nlm.nih.gov/pubmed/37644049
http://dx.doi.org/10.1038/s41467-023-40957-9
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