UCLA

The brain is comprised of neurons, glia, and vascular cells. While all cell types are known to exhibit aging-associated dysfunction, it is unclear whether this occurs simultaneously or sequentially across different cell types. To pinpoint the initial events precipitating subsequent alteration and to devise therapies that can prevent or slow these causative events, it is crucial to map out the progression of dysfunction among multiple cell types during aging. Here, we evaluated the transcriptional timeline of aging-associated brain changes. By analyzing single-cell datasets, we uncovered stage-specific and asynchronous changes across various cell types in the senescent mouse brain. Notably, we found that cell types may demonstrate different timelines of and vulnerabilities to aging-associated transcriptomic changes. We also detected changes in lipid biosynthesis-associated genes in oligodendrocytes as an early event in aging. Our study revealed the asynchrony of aging among different brain cell types and mapped the sequential timeline of events in aging neurons, glia, and vascular cells.