Scientists have discovered a new molecular mechanism that contributes to aging. Six research groups from the University of Cologne Cluster of Excellence on Cellular Stress Responses in Age-Associated Diseases (CECAD), the Max Planck Institute for Biology of Aging (MPI) in Cologne, and the University of Göttingen collaborated to study the transcription process in five different model organisms and a wide variety of tissues. They found that the transcriptional elongation speed of genes increases with age, leading to lower quality of gene products. However, the accuracy of the entire transcription process could be controlled and reversed by dietary restriction or intervention in insulin signaling.

The reading of genes, known as transcription, is essential because it is a primary regulator of protein levels. Although it was known that gene expression changes with age and the control of gene expression may be impaired, it was unclear whether the accuracy of the transcription process changes with age and whether such a change would have relevant consequences for organisms. The researchers investigated genome-wide, age-related changes in transcription processes in nematodes, fruit flies, mice, rats, and humans, including diverse tissues.

The scientists found that the average speed at which the transcript grows through the attachment of RNA building blocks, the nucleotides, increased with age in all five species. Together with the higher speed of this elongation speed, the researchers also observed changes in the so-called splicing, a further work step within the transcription process from the gene to the finished protein, in which the transcription product is once again shortened and cut to size. Prof. Andreas Beyer, CECAD working group leader and professor at the Institute for Genetics of the Faculty of Mathematics and Natural Sciences at the University of Cologne, stated that “Our results uncover fundamental molecular mechanisms underlying animal aging and interventions to extend lifespan, providing clues as to how we might contribute to healthy aging in the future.”

The fact that interventions, such as reduced calorie intake, also have a positive effect on healthy aging on the molecular level by improving the quality of gene transcription is something that the researchers have been able to prove with their study. The lifespan of flies and the division potential of human cells lengthened when the researchers used interventions to reduce the reading speed. The study’s findings provide valuable insights into the molecular mechanisms underlying aging and offer new opportunities for developing treatments to promote healthy aging.

This study was published in Nature.

References

• Debès, C., Papadakis, A., Grönke, S., Karalay, Ö., Tain, L. S., Mizi, A., Nakamura, S., Hahn, O., Weigelt, C., Josipovic, N., Zirkel, A., Brusius, I., Sofiadis, K., Lamprousi, M., Lu, Y.-X., Huang, W., Esmaillie, R., Kubacki, T., Späth, M. R., … Beyer, A. (2023). Ageing-associated changes in transcriptional elongation influence longevity. Nature. https://doi.org/10.1038/s41586-023-05922-y
• University of Cologne. (2023, April 12). Genes are read faster and more sloppily in old age. University of Cologne; University of Cologne. https://portal.uni-koeln.de/en/universitaet/aktuell/press-releases/single-news/genes-are-read-faster-and-more-sloppily-in-old-age