2024-04-13 13:20:11
Scientists have found that certain RNA molecules in brain cells, called long-lived RNA, can persist throughout an organism’s life, playing a critical role in maintaining genome stability and offering insights into brain aging and potential treatments for neurodegenerative diseases.
Neuroscientists at FAU have discovered that certain building blocks in nerve cells can last a lifetime.
Certain RNA molecules in the nerve cells in the brain last a lifetime without being regenerated. Neuroscientists from Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) have now demonstrated that this is the case together with researchers from Germany, Austria and the USA. RNA are usually short-lived molecules that are constantly regenerated to adapt to environmental conditions.
with their findings now published in the journal knowledgeThe research group hopes to unravel the complex aging process of the brain and gain a better understanding of related neurodegenerative diseases.
Most of the cells in the human body renew themselves regularly, thus maintaining their vitality. However, there are exceptions: the heart, pancreas, and brain are made up of cells that do not regenerate throughout life, yet should remain in perfectly normal condition. “Aging neurons are an important risk factor for neurodegenerative diseases such as Alzheimer’s,” says Prof. Dr. Tomohisa Toda, professor of neural epigenomics at FAU and at the Max Planck Center for Physics and Medicine in Erlangen. “A basic understanding of the aging process and which key components are involved in maintaining cell function is essential for effective treatment concepts.”
Discovery of long RNAs
In a joint study conducted together with neuroscientists from Dresden, La Jolla (USA) and Mechelensburg (Austria), the working group led by Toda has now identified a key component of brain aging: the researchers were able to demonstrate for the first time that certain types of ribonucleic acid (RNA) that protect the substance The genetics have existed exactly as long as the neurons themselves. “It’s surprising, unlike DNA that never changes at all, most RNA molecules are very short and are replaced all the time,” Toda explains.
In order to determine the lifespan of the RNA molecules, Toda’s group worked together with the team of Prof. Dr. Martin Hatzer, a cell biologist at the Austrian Institute of Science and Technology (ISTA). “We were able to label the RNA with fluorescent molecules and track its lifespan their life in mouse brain cells,” explains Tomohisa Toda, who has a unique expertise in epigenetics and neurobiology and who won an ERC Consolidator grant for his research in 2023. “We were even able to detect the long-lived marked RNA in two-year-old animals, and not just in their neurons, but also in mature somatic neural stem cells in the brain.”
In addition, the researchers discovered that the long-lived RNA, which they called LL-RNA for short, tend to be located in the cell nuclei, closely related to chromatin, a complex of DNA and proteins that forms chromosomes. This suggests that LL-RNA plays a key role in chromatin regulation. In order to confirm this hypothesis, the team reduced the concentration of LL-RNA in an in vitro experiment with mature neural stem cell models, resulting in severely compromised chromatin integrity.
“We are convinced that LL-RNA plays an important role in the long-term regulation of genome stability and therefore in the lifelong preservation of nerve cells,” explains Tomohisa Toda. “Future research projects should give deeper insight into the biophysical mechanisms behind the long-term preservation of LL-RNA. We want to find out more about their biological function in chromatin regulation and what effect aging has on all these mechanisms.”
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