A comprehensive analysis of age-related metabolomics and transcriptomics reveals metabolic alterations in rat bone marrow mesenchymal stem cells

Abstract

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 combinedapplication of metabolomics and transcriptomics technologies can effectively describe the possible molecularmechanisms of rat bone marrow mesenchymal stem cell (BMSC) senescence. Metabolomic profiles revealed 23differential metabolites which were abundant in “glycerophospholipid metabolism”, “linoleic acid metabolism”and “biosynthesis of unsaturated fatty acids”. In addition, transcriptomics analysis identified 590 genes withenormously differential expressions in young and old BMSCs. KEGG enrichment analyses showed thatmetabolism‐related pathways in BMSC senescence had stronger responses. Furthermore, the integratedanalysis of the interactions between the differentially expressed genes (DEGs) and metabolites indicated thedifferential genes related to lipid metabolism of Scd, Scd2, Dgat2, Fads2, Lpin1, Gpat3, Acaa2, Lpcat3, Pcyt2 andPla2g4a may be closely associated with the aging of BMSCs. Finally, Scd2 was identified as the most significantDEG, and Scd2 over‐expression could alleviate cellular senescence in aged BMSCs. In conclusion, this workprovides a validated understanding that the DEGs and metabolites related to lipid metabolism present moreapparent changes in the senescence of rat BMSCs