Studies on aging have largely included one or two OMICS layers, which may not necessarily reflect the signatures of other layers. Moreover, most aging studies have often compared very young (4-5 wks) mice with old (24 months) mice which does not reflect the aging transition after the attainment of adulthood. Therefore, we aimed to study and compared muti-OMICS aging signatures across key metabolic tissues of mature adults (6 months) and old (24 months) C57BL/6J mice (the most commonly used mouse strain). Here we compared the differentially regulated genes and enriched pathways for transcriptome, proteome and epigenome (H3K27ac, H3K4me3, H3K27me3, DNA methylation) across liver, heart, and quadriceps muscle. The major aging associated pathways cross multiple layers and tissues are decreased RNA metabolism, transcription, and translation at transcript and protein levels however increased potential of transcription at DNA methylation and H3K27ac levels.