A team led by neuroscientists from Friedrich-Alexander-Universität Erlangen-Nürnberg have found that certain types of RNA molecules in the nerve cells of the brain last a lifetime without being renewed, unlike most other cells in the human body. The findings shed light on the complex aging process of the brain and should lead to a better understanding of related degenerative diseases.
Most cells in the human body are regularly renewed, but there are exceptions, such as the heart, pancreas, and brain, which consist of cells that do not renew throughout the whole lifespan. The team’s finding that certain types of RNA that protect genetic material exist just as long as the neurons themselves is surprising, as most RNA molecules are extremely short-lived and are constantly being exchanged.
To determine the life span of the RNA molecules, the team worked with a group from the Institute of Science and Technology Austria. “We succeeded in marking the RNAs with fluorescent molecules and tracking their lifespan in mice brain cells,” explains Tomohisa Toda, senior author of the study published in Science. “We were even able to identify the marked long-lived RNAs in two year old animals, and not just in their neurons, but also in somatic adult neural stem cells in the brain.”
The researchers also discovered that the LL-RNAs tend to be located in the cells' nuclei, closely connected to chromatin, a complex of DNA and proteins that forms chromosomes. This indicates that LL-RNAs play a key role in regulating chromatin. When the researchers reduced the concentration of LL-RNA in an in vitro experiment with adult neural stem cell models, the integrity of the chromatin was strongly 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,” adds Toda. “Future research projects should give a deeper insight into the biophysical mechanisms behind the long-term conservation of LL-RNAs. We want to find out more about their biological function in chromatin regulation and what effect aging has on all these mechanisms.”