Researchers at the University of California San Diego (UCSD) have discovered that different types of brain cells may age at different speeds, a finding that could illuminate the development of Alzheimer’s disease. Using advanced technology to analyze postmortem brains of 14 donors over the age of 59, some of whom had Alzheimer’s, the team found significant differences in how DNA interacts with RNA in brain cells from the frontal cortex.
The study, published in Nature, utilized a tool called MUSIC (multi-nucleic acid interaction mapping in single cells) to examine the chromosomes of individual cells. This technology allowed researchers to observe interactions between DNA, RNA, and proteins, collectively known as chromatin. They found that in brain cells showing signs of aging and Alzheimer’s, the DNA had fewer intimate interactions with RNA, suggesting a disruption in genetic translation and gene expression.
Bioengineer Sheng Zhong from UCSD highlighted the potential of this technology to uncover new molecular mechanisms underlying Alzheimer’s pathology, which could lead to more targeted therapeutic interventions. The research indicates that changes in chromatin structure, previously observed in animal models, also occur at the single-cell level in humans and are linked to aging and neurodegeneration.
Interestingly, the study revealed sex differences in brain cell aging. The female brain showed fewer aged neurons but more aged oligodendrocytes compared to the male brain. Further experiments in mice supported these findings, indicating that oligodendrocytes aged faster in female mice, which could explain why women are twice as likely to develop late-onset Alzheimer’s.
The team speculates that understanding the dysregulated genes in these aged cells could identify new therapeutic targets. UCSD bioinformatics researcher Xingzhao Wen expressed hope that this knowledge could lead to breakthroughs in treating or preventing Alzheimer’s disease.
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