Exploring the Molecular Mechanisms of Aging with Bioinformatics Experts

A team led by bioinformatics experts Andreas Keller and Fabian Kern from Saarland University together with researchers at Stanford University have gained new insights into the manifestations of aging at the molecular level. They found that the process of reading genetic information does not proceed as smoothly in older individuals as it does in younger ones.

These changes in the transcription process are due to specific RNA molecules that influence the activity of individual genes and thus determine which proteins are produced by the body – physiological changes that can have a significant impact on the body’s metabolism. Their research has now been published in the journal Nature Biotechnology.

How and why do our organs age? To help answer this question, a group of researchers from Saarbrücken and Stanford have studied part of the molecular mechanisms that underlie aging. A team led by Andreas Keller, professor of clinical bioinformatics at the University of Saarbrücken, examined the organs of mice across mouse lifespans and found that the amount of small non-coding RNAs (sncRNAs) expressed in the organs varied greatly depending on the age of the mice. mice.

“We have identified a number of RNA molecules whose abundance increases with age, as well as those whose abundance decreases dramatically,” said Andreas Keller, who also heads a research team in the Department of Clinical Bioinformatics at the Helmholtz Institute for Pharmaceutical Research. Saarland (HIPS). HIPS is a branch of the Helmholtz Research Center for Infection (HZI) in Braunschweig and is jointly run by Saarland University.

Some sncRNA molecules specifically regulate the amounts of mRNA molecules. Messenger RNA molecules carry the genetic instructions encoded in the genome (DNA) to the cell’s protein-making machinery. They essentially make copies of segments of DNA in the cell – a process known as transcription. Thus, mRNA encodes the chemical blueprint used to produce individual proteins, which in turn control most metabolic processes in the body.

“If you compare an organism’s DNA to a cookbook containing all the protein recipes, the messenger RNA copies the individual recipes from which the corresponding dishes (proteins) are created,” explained Victoria Wagner, a biotechnologist and lead author of the paper presenting the research findings. Team search. But if the mRNA molecules are blocked by other RNAs, the translation process is inhibited, causing no more proteins to be produced.

“If protein production is inhibited, this affects the metabolism of cells and organs and will eventually also affect the aging process of the entire organism,” Wagner explained.

The research team in Saarbrücken was able to describe the molecular signatures and patterns associated with aging. Some of these molecular markers are general in nature, i.e. identified in every organ studied, and others have been found specific to individual organs.

“A particular molecule showed very strong effects in the liver,” said Professor Andreas Keller, who with his team at Saarbrücken used bioinformatics software to analyze the huge amounts of sequencing data generated. “Other experiments have shown the surprising finding that some of the mechanisms involved are reversible — at least at the molecular level.”

In future research, bioinformatics scientists plan to examine the RNA molecules more closely, and hope they can be used to develop signs of aging of specific organs. “By developing this type of biomarker, we hope to be able to monitor the aging process in individuals by examining their blood,” Keller said. This could be a particularly interesting development, since the aging process is still one of the main causes of many of the most common diseases.

This potentially opens up a number of other opportunities in biomedicine. “We know that infectious diseases can sometimes put our cells under tremendous stress and this can accelerate aging,” said Fabian Kern, HIPS Junior Research Group Lead.

Kern, who has a PhD in bioinformatics, was instrumental in developing the software tools used in the study and explained the significance of the current research as follows: “Using the latest machine learning methods and techniques, we can accurately classify different molecular signaling pathways. From the knowledge gained, we hope In devising new approaches to develop innovative drug products, we are therefore already at an early stage in the drug discovery process. While traditional drug agents act at the level of proteins, our approach will involve targeted changes at the level of messenger RNA.”