Long-Lived RNA Molecules Found in Nerve Cells Provide Insights on Aging Process of the Brain

Ribonucleic acid (RNA) is a genetic material present in most living organisms and viruses. It plays an important role in converting DNA's genetic information into proteins.

Although nuclear RNAs are vital in proper chromatin structure and transcription regulation, their life span has not been determined in adult tissues.

Cell Renewal

The majority of the cells in the human body are renewed regularly to maintain their vitality. Some exceptions are the cells in the brain, heart, and pancreas. They do not renew throughout their entire lifespan, yet they are expected to maintain their full working order.

Aging neurons inside the brain are a crucial risk factor for neurodegenerative disorders such as Alzheimer's disease. Understanding the aging process and the key components in maintaining cell functions is important in developing effective treatment options.

Non-Aging RNAs

Generally, RNAs are short-lived molecules that are constantly reconstructed to adjust to environmental conditions. In a recent study, however, scientists from Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), in collaboration with experts from Germany, Austria, and the US, have discovered certain molecules in the nerve cells that last a lifetime in the brain without being renewed. The details of their study are described in the paper "Lifelong persistence of nuclear RNAs in the mouse brain."

A joint study conducted by FAU and neuroscientists from Dresden, La Jolla (USA), and Klosterneuburg (Austria) has identified the key component of brain aging. Dr. Tomohisa Toda, Professor of Neural Epigenomics at FAU and the Max Planck Center for Physics and Medicine in Erlangen, led the working group.

For the first time, scientists were able to demonstrate that certain types of RNA that defend genetic material exist just as long as the neurons themselves. This is surprising since the majority of RNA molecules have a short lifespan and are being changed constantly.

Prof. Toda determined the lifespan of the RNA molecules by working together with the team led by Dr. Martin Hetzer, a cell biologist at the Institute of Science and Technology Austria (ISTA). They succeeded in marking the RNAs with fluorescent molecules and tracking their lifespan in the brain cells of mice.

The research team was even able to identify the marked long-lived RNA molecules, also called LL-RNA, in two-year-old animals. They were detected not just in their neurons but also in somatic adult neural stem cells in the brain.

In addition, it was found that long-lived RNAs tend to be located in the nuclei of cells. They are closely related to chromatin, a complex of DNA and proteins that forms chromosomes. This indicates the critical role played by LL-RNA in regulating chromatin.

To confirm this hypothesis, the research team reduced the concentration of LL-RNA in an in-vitro experiment with adult neural stem cell models. The findings suggest that the integrity of the chromatin was strongly impaired.

According to Dr. Toda, they are convinced that LL-RNAs play an essential role in the long-term regulation of genome stability and the life-long conservation of nerve cells. The research team hopes that their findings will unlock the brain's complex aging process and better understand related degenerative diseases.

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