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Martin Hetzer, a molecular biologist and president of the Institute of Science and Technology Austria (ISTA), along with colleagues, discovered that RNA molecules, typically transient, can remain stable in the nerve cells of mice for their entire lives. This groundbreaking research, published in Science, sheds light on the complexities of brain aging and diseases associated with it. Hetzer, who recently returned to Austria from the United States, has a keen interest in understanding the aging processes in various organs and their implications for health.

The human brain consists of nerve cells (neurons) that can be as old as the organism itself, lingering for over a century without renewal. This longevity of neurons poses a risk factor for neurodegenerative disorders like Alzheimer’s disease. To combat the effects of aging on these cells, a deeper understanding of their functioning over time is crucial. The recent study by Hetzer and his team provides new insights into the mechanisms that allow RNA molecules to persist throughout a mouse’s lifespan. This reveals the importance of long-lived key molecules in maintaining a cell’s function.

In a dynamic cellular environment, some components are constantly renewed, while others remain unchanged over time. DNA, for example, found in the nucleus of cells, remains the same throughout an organism’s life. In contrast, RNA molecules, especially messenger RNA (mRNA), are known for their transient nature. In this study, the researchers identified a group of non-coding RNAs that play essential roles in cellular organization and function. Surprisingly, these RNAs were found to be long-lived, persisting for the entire lifespan of the mice.

Through advanced labeling techniques, Hetzer and his team were able to track the long-lived RNAs in the brains of newborn mice and monitor their concentrations over time. They observed that these molecules were present in various cell types within the brain, but were particularly prominent in neurons. The researchers discovered that long-lived RNAs accumulate near the heterochromatin, a region of the genome that contains inactive genes. Further experiments revealed the crucial role of these RNAs in maintaining genome stability and cellular longevity.

By reducing the levels of long-lived RNAs in neuronal cells, the scientists were able to demonstrate the impact on the cells’ viability and genome stability. The study suggests that these molecules play a vital role in regulating genome stability over a lifetime. However, the exact mechanism by which long-lived RNAs interact with the heterochromatin and maintain cellular function remains to be elucidated. Hetzer’s future research aims to uncover these missing links and further explore the biological characteristics of long-lived RNAs for potential therapeutic interventions in aging-related disorders.

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