Authors
Cédric Debès, Antonios Papadakis, Sebastian Grönke, Özlem Karalay, Luke S Tain, Athanasia Mizi, Shuhei Nakamura, Oliver Hahn, Carina Weigelt, Natasa Josipovic, Anne Zirkel, Isabell Brusius, Konstantinos Sofiadis, Mantha Lamprousi, Yu-Xuan Lu, Wenming Huang, Reza Esmaillie, Torsten Kubacki, Martin R Späth, Bernhard Schermer, Thomas Benzing, Roman-Ulrich Müller, Adam Antebi, Linda Partridge, Argyris Papantonis, Andreas Beyer
Publication date
2023/4/27
Journal
Nature
Volume
616
Issue
7958
Pages
814-821
Publisher
Nature Publishing Group UK
Description
Physiological homeostasis becomes compromised during ageing, as a result of impairment of cellular processes, including transcription and RNA splicing, , –. However, the molecular mechanisms leading to the loss of transcriptional fidelity are so far elusive, as are ways of preventing it. Here we profiled and analysed genome-wide, ageing-related changes in transcriptional processes across different organisms: nematodes, fruitflies, mice, rats and humans. The average transcriptional elongation speed (RNA polymerase II speed) increased with age in all five species. Along with these changes in elongation speed, we observed changes in splicing, including a reduction of unspliced transcripts and the formation of more circular RNAs. Two lifespan-extending interventions, dietary restriction and lowered insulin–IGF signalling, both reversed most of these ageing-related changes. Genetic variants in RNA polymerase II …
Total citations
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