Crocetin restored the expression of multiple genes in the hippocampi of old mice to bring it closer to young mice
To know whether crocetin can restore the expression of hippocampi genes of old mice to the levels of young mice; we compared the gene expression profile of crocetin, control (untreated aged), and young mice groups. The hippocampi transcriptome data of young mice were taken from GEO NCBI (GSE147842) (Haghani et al., 2020).
The cluster dendrogram revealed three gene clusters viz. crocetin, aged control, and young mice. Wherein, crocetin cluster was closer to young mice as compared to aged mice, indicating the prevention of brain aging in crocetin group (Figure 4A). DSeq2 analysis revealed that most of the mitochondrial genome encoded ETC genes ND1, ND2, ND4, ND5, ND6, CYTB, COX1, and COX3 were significantly downregulated in aged hippocampi compared to young mice (Figure 4B). Further, crocetin treatment of aged mice clearly showed a significant improvement in the expression of these genes (Figure 4B). Interestingly, the expression of the genes Bdnf, Gabbr2, Gad2, Gfpt1, Drosha, and Uqcrq were found to have significantly high expression in young and crocetin treated group in comparison to untreated control mice (Figure 4B and Supplementary Spreadsheet SS3). We also confirmed the upregulation of two essential genes, ND5 and ND6 of ETC through western blotting, which confirmed our findings of functional upregulation of ETC (Figure 4C).