Effects of aging on diurnal transcriptome change in the mouse corpus callosum

The corpus callosum, a major white matter region central to cognitive function, is vulnerable to aging. Using zeitgeber time (ZT) aligned with environmental light/dark cycles, we investigated temporal gene expression patterns in the corpus callosum of young (5-month-old) and aged (24-month-old) mice using RNA-seq. Comparative analysis revealed more differentially expressed genes across ZT pairs in young mice than aged mice. In addition, complement pathway genes, including C4b, C3, C1qa, C1qb, and C1qc, were consistently upregulated in aged mice regardless of ZT. Furthermore, genes such as Etnppl, Tinagl1, Hspa12b, Ppp1r3c, Thbd, Pla2g3, and Tsc22d3 exhibited ZT-dependent rhythmicity in young mice, but their rhythmic patterns were altered with age. This study provides an important dataset of the interplay between aging, diurnal rhythms, and gene expression in the corpus callosum, highlighting potential molecular mechanisms mediating white matter aging. Further investigation is warranted to dissect these gene's specific roles in neurological health during aging.