Downregulation of transposable elements extends lifespan in Caenorhabditis elegans

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作者
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
Tibor Vellai
机构
[1] Eötvös Loránd University (ELTE),Department of Genetics
[2] Eötvös Loránd Research Network (ELKH)-ELTE Genetics Research Group,Synthetic and Systems Biology Unit
[3] HCEMM-BRC Metabolic Systems Biology Research Group,Laboratory of Structural Chemistry and Biology & Hungarian Academy of Sciences (MTA)
[4] Institute of Biochemistry,ELTE Protein Modelling Research Group, Institute of Chemistry
[5] Biological Research Centre,Division of Medical Biotechnology
[6] Eötvös Loránd Research Network (ELKH),undefined
[7] Institute for Computer Science and Control (SZTAKI),undefined
[8] Brigham and Women’s Hospital & Harvard Medical School,undefined
[9] Eötvös Loránd University,undefined
[10] Paul Ehrlich Institute,undefined
[11] Vellab Biotech Ltd.,undefined
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摘要
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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