Abstract
Mice lacking caveolin-1 (Cav1), a key protein of plasma membrane, exhibit brain aging at an early adult stage. Here, integrative analyses of metabolomics, transcriptomics, epigenetics, and single-cell data were performed to test the hypothesis that metabolic deregulation of fetal brain due to the ablation of Cav1 is linked to brain aging in these mice. The results of this study show that lack of Cav1 caused deregulation in the lipid and amino acid metabolism in the fetal brain, and genes associated with these deregulated metabolites were significantly altered in the brain upon aging. Moreover, ablation of Cav1 deregulated several metabolic genes in specific cell types of the fetal brain and impacted DNA methylation of those genes in coordination with mouse epigenetic clock. The findings of this study suggest that the aging program of brain is confounded by metabolic abnormalities in the fetal stage due to the absence of Cav1.