Cortical bulk RNA sequencing of APOE-TR mice under calorie restriction and normal diet

Using preprocessed gene expression profiles, we conducted weighted gene co-expression network analyses (WGCNA) and differential gene expression analyses. Consistently across both approaches, our results revealed an upregulation of the cholesterol synthesis pathway in E3- and E4-CR mice, but not in E2-CR mice. CR related DEGs also predicted the enhanced myelination, which were further validated through immunofluorescent staining for PDGFRA (an OPC marker), ASPA (an OL marker), and MBP (a myelin sheath protein), as well as electron microscopy of corpus callosum tissues in E3- and E4-CR mice, but not in E2-CR mice.

Overall, our study highlights the critical role of APOE genotype in modulating the brain’s response to CR, emphasizing the importance of considering APOE genotype in developing prevention strategies for aging and age-related disorders.