*2.5. KOG and KEGG Enrichment and Analyses*

KOG was used to functionally classify mRNAs (766) regulated by the 19 exosomal miRNAs that were differentially expressed between young and old rats. Among the resultant 25 KOG classifications, genes involved in "signal transduction mechanisms" were the ones most commonly targeted (151 genes), followed by "general function prediction only" (119 genes), "transcription" (56 genes), "posttranslational modification and protein turnover" (55 genes), and "intracellular function and secretion and vesicular transport "(40 genes) (Figure 4B).

KEGG is a comprehensive knowledge base for both functional interpretation and practical application of genomic information [34]. KEGG pathway analysis identified 20 pathways that differed significantly (*p* < 0.05) between exosomes of young and old rats (Figure 4C). Among these pathways, the following were found to be involved in aging and lifespan: insulin resistance, mitogen-activated protein kinase (MAPK) signaling, PI3 kinase (PI3K)–Akt signaling, mammalian target of rapamycin (mTOR) signaling, toll-like receptor signaling, FoxO signaling, ErbB signaling, longevity-regulating signaling, and resistance to inhibitors of epidermal growth-factor receptor (EGFR) tyrosine kinase (Figure 4C).
