Raised gene reading speed problematic

Artist’s rendering of the transcription. © selvanegra/iStock

According to a study, a “sloppy” reading of genes apparently contributes to aging: With increasing age, genetic information is implemented more quickly, which means that the quality of the gene products suffers. This emerges from an examination of the transcription processes in four model animal species and human cell cultures. The scientists report that there are also opportunities to limit the acceleration and thus the aging effect.

We are born, develop and, as is well known, after a certain age a degradation process begins. As natural as aging may seem to us, from a scientific perspective it raises many questions. One thing is clear: One of the basics is the increasing impairment of processes at the cellular level. With increasing age, the concentration and quality of protein molecules, which act as building blocks or fulfill functions in cells and the whole body, decrease. The production of these proteins is based on the conversion of the information encoded in the genes.

On the trail of molecular aspects of aging

It was already known that this so-called gene expression changes with age, whereby impairments in the control functions of this process can also play a role. This refers to the so-called transcription: During this reading process, genetic information is brought into a form that serves the cellular machinery as a blueprint for protein production. So far, however, it has remained unclear to what extent the transcription process actually changes with age and what consequences this could have for the organism.

Six German teams of scientists have now investigated these questions as part of a joint project on aging research. In this way, they were able to combine results from five creatures: roundworms, fruit flies, mice, rats and humans. “Only by combining our expertise was it possible to study so many creatures and types of data,” says senior author Andreas Beyer from the University of Cologne. The results are largely based on modern molecular genetic methods, which also allow conclusions to be drawn about the dynamics of transcription processes.

Fast – but careless

One might think that processes slow down with increasing age – but the opposite is evidently the case at the molecular level, as the researchers found out: the average rate at which the read-off product – the messenger RNA – grows during transcription increases. Specifically: The protein responsible for this, RNA polymerase II, attaches faster nucleotides to the RNA strand with increasing age. The scientists were able to demonstrate this effect in all five species examined. It was also shown that this increased speed is associated with a decline in the quality of such gene copies. “Sloppy” products are emerging – the researchers found, for example, an increased formation of circular RNAs.

The team was also able to show that the speed and accuracy of the reading process can be influenced. Interestingly, this was made possible by measures that are already known to help extend the lifespan of organisms: dietary restriction or interference with insulin metabolism. “With our study, we have now been able to clearly demonstrate that interventions, such as reduced calorie intake, also have a positive effect on a healthy aging process at the molecular level in the form of qualitatively better gene reading,” says Beyer.

The scientists were also able to show that the lifespan of flies and the potential for human cells to divide can be increased if they deliberately slow down the reading speed through certain manipulations. The researchers say that further potential for aging research and medicine is now emerging: “Our results reveal fundamental molecular mechanisms that underlie the aging of living beings and interventions to extend lifespan, and thus provide indications of possible measures how we can contribute to healthy aging in the future,” concludes Beyer.

Source: University of Cologne, specialist article: Nature, doi: 10.1038/s41586-023-05922-y

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