As animals and people age, there are changes in the genome. Telomeres, the protective ends of chromosomes, get shorter as cells continue to divide; some cells will pick up mutations in their genomes from things like UV rays or pollution, for example. New research has shown that gene transcription, in which active genes are copied into messenger RNA (mRNA) molecules, gets faster but sloppier as organisms age too. The findings, which were confirmed in five organisms, have been reported in Nature.
Transcription is a vital process that can impact so many biological processes because it affects the level and quality of the proteins that are made in a cell. Proteins are at the heart of nearly every biochemical function. Aging can impair gene expression in many ways, which researchers have previously shown.
This work has revealed, however, that the accuracy of transcription is also affected by aging, to a degree that affects biology. The researchers analyzed how transcription changed with aging in various tissues in nematode worms, fruit flies, mice, rats, and humans. The average speed of the extension of a gene transcript, as nucleotides are added to the mRNA molecule, was found to increase with age in each of the five species.
As an enzyme called RNA polymerase II increased its speed, there were alterations in RNA splicing, in which mRNA transcripts are edited after transcription but before they are translated into proteins.
"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," said study co-author 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.
The researchers were also able to tinker with transcription accuracy throughout the process by modifying diet or insulin signaling, which are both known to affect lifespan. The division potential of human cells growing in culture and the lifespan of fruit flies was also lengthened when the researchers lowered the reading speed.
We know that interventions like a reduced calorie diet can also promote healthier aging processes at the molecular level. This study has shown "quite clearly" that these interventions are working by improving the quality of gene transcripts, added Beyer.
Sources: University of Cologne, Nature