Engineers at the University of California San Diego have found that certain brain cells age more rapidly than others and are more common in individuals with Alzheimer’s disease. They also discovered sex-specific differences in the aging process of these brain cells, with the female cortex showing a higher ratio of “old” oligodendrocytes to “old” neurons compared to the male cortex. These findings were made possible through a new technique called MUSIC, which allows researchers to map interactions between chromatin and RNA inside individual brain cells.
The research, detailed in a paper published in Nature, offers a deeper understanding of Alzheimer’s disease and the molecular mechanisms underlying its pathology. The MUSIC technique provides a unique view into the complexities of the human brain, revealing how interactions between chromatin and RNA change as brain cells age. By studying postmortem brain samples from donors with and without Alzheimer’s disease, the researchers were able to identify patterns of interactions that were associated with aging and disease.
The potential impact of these discoveries extends to the development of new treatments for Alzheimer’s disease. By identifying dysregulated genes in aged brain cells and understanding their functions within the chromatin structure, researchers hope to pinpoint new therapeutic targets. Additionally, the study revealed sex-specific differences in the aging of brain cells, with the female cortex showing an increased presence of aged oligodendrocytes compared to aged neurons. This disparity could have implications for cognitive decline and the increased risks of neurodegenerative disorders in women.
Moving forward, the researchers plan to further optimize the MUSIC technique to identify factors responsible for accelerated aging in specific brain cells, such as regulatory genes and gene circuits. By targeting these factors, they hope to develop strategies to mitigate the aging process in the brain. The study is supported by the National Institutes of Health and a Kruger Research grant, with Sheng Zhong being a founder and shareholder of Genemo, Inc. while the other authors declare no competing interests.
Overall, this research sheds light on the complexities of Alzheimer’s disease and brain aging, with implications for potential therapeutic interventions. By unraveling the interactions between chromatin and RNA in individual brain cells, researchers have identified patterns associated with aging and disease. The sex-specific differences in aging of brain cells further highlight the need for tailored treatments for neurodegenerative disorders. With continued research and optimization of the MUSIC technique, the hope is to uncover new targets for intervention in Alzheimer’s disease and other age-related cognitive decline.