A comprehensive analysis of age-related metabolomics and transcriptomics reveals metabolic alterations in rat bone...

The functions of stem cells decline progressively with aging, and some metabolic changes occur during the process. However, the molecular mechanisms of stem cell aging remain unclear. In this study, the combined application of metabolomics and transcriptomics technologies can effectively describe the possible molecular mechanisms of rat bone marrow mesenchymal stem cell (BMSC) senescence. Metabolomic profiles revealed 23 differential metabolites which were abundant in "glycerophospholipid metabolism", "linoleic acid metabolism" and "biosynthesis of unsaturated fatty acids". In addition, transcriptomics analysis identified 590 genes with enormously differential expressions in young and old BMSCs. KEGG enrichment analyses showed that metabolism-related pathways in BMSC senescence had stronger responses. Furthermore, the integrated analysis of the interactions between the differentially expressed genes (DEGs) and metabolites indicated the differential genes related to lipid metabolism of Scd, Scd2, Dgat2, Fads2, Lpin1, Gpat3, Acaa2, Lpcat3, Pcyt2 and Pla2g4a may be closely associated with the aging of BMSCs. Finally, Scd2 was identified as the most significant DEG, and Scd2 over-expression could alleviate cellular senescence in aged BMSCs. In conclusion, this work provides a validated understanding that the DEGs and metabolites related to lipid metabolism present more apparent changes in the senescence of rat BMSCs.