Certain RNA molecules within the brain’s nerve cells persist throughout life without being renewed. Neuroscientists at the Friedrich-Alexander Erlangen-Nuremberg University (FAU), along with researchers from Germany, Austria and the United States, have demonstrated that this is true. RNA is generally a short-lived molecule, constantly remodeling to adapt to environmental conditions. The findings are published in the journal Science, and the researchers hope to decipher the brain’s complex aging process and better understand related degenerative diseases.
Most cells in the human body are renewed regularly, thereby maintaining vitality. However, there are exceptions. The heart, pancreas, and brain are made up of cells that do not regenerate throughout life, but still need to remain fully functional. “Neuron aging is an important risk factor for neurodegenerative diseases such as Alzheimer’s disease,” says Professor Tomohisa Toda, Professor of Neuroepigenomics at the Max Planck Center for Physical Medicine at FAU and Erlangen. “A fundamental understanding of the aging process and which key elements are involved in maintaining cellular function is critical for effective therapeutic concepts.”
In a collaborative study conducted with neuroscientists from Dresden, La Jolla (USA), and Klosterneuburg (Austria), a working group led by Toda identified key factors in brain aging. For the first time, researchers were able to demonstrate that: The specific type of ribonucleic acid (RNA) that protects genetic material has been around for as long as neurons themselves. “This is surprising because unlike DNA, which in principle never changes, most RNA molecules have a very short lifespan and are constantly replaced,” Professor Toda explains.
To determine the lifespan of RNA molecules, the Toda group collaborated with the team of cell biologist Professor Martin Hetzer from the Austrian Institute of Science and Technology (ISTA). “We have successfully labeled RNA with fluorescent molecules and tracked its lifespan in mouse brain cells,” says the author, who has unique expertise in epigenetics and neurobiology and plans to study in 2023. Tomohisa Toda, who received the ERC Consolidator Grant for the project, explains: They were able to identify significant long-lived RNAs not only in the neurons of the two-year-old animals, but also in adult somatic neural stem cells in the brain. ”
Additionally, researchers have found that long-lived RNAs (abbreviated as LL-RNAs) tend to reside in the nucleus of cells and are closely associated with chromatin, the complex of DNA and proteins that forms chromosomes. discovered. This indicates that LL-RNA plays an important role in regulating chromatin. To confirm this hypothesis, the researchers lowered the concentration of LL-RNA in an in vitro experiment using an adult neural stem cell model and found that chromatin integrity was severely compromised.
“We believe that LL-RNA plays an important role in the long-term control of genome stability and thus the lifelong preservation of neurons,” explains Tomohisa Toda. “Future research projects should provide deeper insight into the biophysical mechanisms behind the long-term storage of LL-RNA. We want to learn more about how aging affects all these mechanisms.”
