Brain aging mediates region-specific transcriptomic alterations.

Abstract

Brain aging is commonly associated with multiple neurological malfunctions and neurodegenerative diseases, which are mostly induced by transcriptomic abnormalities in brain tissues. Therefore, analyses of the transcriptomic differences between different regions of young and aged brains are essential for elucidating the key genes and biological processes mostly dysregulated during brain aging. Here, we conducted a comprehensive transcriptomic analysis of RNA-seq data generated from the cortex and hippocampus of 1-month-old (young) and 22-month-old (aged) mice. Interestingly, we found that aging mediates region-specific gene expression and alternative splicing differences in mouse brain. Despite these differences, differentially expressed genes and alternatively spliced transcripts in both regions were enriched for processes essential to neuronal structure and functions, respectively. Our data analyses suggest that these region-specific candidates have a dual regulatory role in shaping the molecular alterations associated with brain aging. Our comprehensive transcriptomic profiling of young and aged mouse brain tissues provides a foundation for future works aiming to elucidate the pathophysiology of brain aging and identify therapeutic targets for neurodegenerative diseases.