Lifelong RNA Molecules Hold the Key to Long-lived Brain Cells

In a groundbreaking study, neuroscientists from Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) and collaborators from Germany, Austria, and the USA have discovered that certain RNA molecules in brain cells last a lifetime without being renewed.

This finding, published in the journal Science, sheds light on the complex aging process of the brain and could lead to a better understanding of neurodegenerative diseases like Alzheimer’s.

Most cells in the human body are regularly replaced to maintain their vitality, but there are exceptions. The heart, pancreas, and brain consist of cells that do not renew throughout an individual’s lifespan, yet they must remain fully functional. Prof. Dr. Tomohisa Toda, Professor of Neural Epigenomics at FAU and the Max Planck Center for Physics and Medicine in Erlangen, emphasizes the importance of understanding the aging process and the key components involved in maintaining cell function for developing effective treatment strategies.

The research team, led by Prof. Toda, identified a crucial component of brain aging: certain types of ribonucleic acid (RNA) that protect genetic material exist as long as the neurons themselves. This discovery is surprising because, unlike DNA, which generally remains unchanged, most RNA molecules are extremely short-lived and constantly being replaced.

To determine the lifespan of these RNA molecules, the Toda group collaborated with cell biologist Prof. Dr. Martin Hetzer and his team at the Institute of Science and Technology Austria (ISTA). They marked the RNAs with fluorescent molecules and tracked their lifespan in mouse brain cells. Remarkably, they identified the marked long-lived RNAs, which they termed “LL-RNA,” in two-year-old animals, not only in their neurons but also in somatic adult neural stem cells in the brain.

The researchers also found that LL-RNAs tend to be located in the cell nucleus, closely connected to chromatin, a complex of DNA and proteins that forms chromosomes. This suggests that LL-RNAs play a key role in regulating chromatin. To confirm this hypothesis, the team reduced the concentration of LL-RNA in an in-vitro experiment with adult neural stem cell models and observed that the integrity of the chromatin was significantly impaired.

“We are convinced that LL-RNAs play an important role in the long-term regulation of genome stability and therefore in the life-long conservation of nerve cells,” explains Tomohisa Toda, who was awarded an ERC Consolidator Grant for his research in 2023.

The research team plans to conduct future studies to gain a deeper understanding of the biophysical mechanisms behind the long-term conservation of LL-RNAs and their biological function in chromatin regulation. They also aim to investigate the effects of aging on these mechanisms.

By unraveling the secrets of LL-RNAs and their role in maintaining the longevity of brain cells, this study opens new avenues for understanding the complex process of brain aging and potentially developing more effective treatments for neurodegenerative diseases. As scientists continue to explore the intricate workings of the brain, discoveries like this bring us one step closer to unlocking the mysteries of the mind and improving the quality of life for those affected by age-related brain disorders.

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