Objectives: Evidences have suggested that the metabolic function is the key regulator to the fate of MSCs, but its function in senescence of MSC and the underlying mechanism is unclear. Therefore, the purpose of this study was to investigate the metabolic activity of MSCs and its possible mechanism during aging.
Materials and methods: We used the Seahorse XF24 Analyzer to understand OCR and ECAR in BMSCs and used RT-PCR to analyze the gene expression of mitochondrial biogenesis and key enzymes in glycolysis. We analyzed BMSC mitochondrial activity by MitoTracker Deep Red and JC-1 staining, and detected NAD+/NADH ratio and ATP levels in BMSCs. Microarray and proteomic analyses were performed to detect differentially expressed genes and proteins in BMSCs. The impact of aging on BMSCs through mitochondrial electron transport chain (ETC) was evaluated by Rotenone and Coenzyme Q10.
Results: Our results demonstrated that the oxidative phosphorylation and glycolytic activity of BMSCs in aged mice were significantly decreased when compared with young mice. BMSCs in aged mice had lower mitochondrial membrane potential, NAD+/NADH ratio, and ATP production than young mice. FABP4 may play a key role in BMSC senescence caused by fatty acid metabolism disorders.
Conclusions: Taken together, our results indicated the dysfunction of the metabolic activity of BMSCs in aged mice, which would play the important role in the impaired biological properties. Therefore, the regulation of metabolic activity may be a potential therapeutic target for enhancing the regenerative functions of BMSCs.
Keywords: aging; bone marrow mesenchymal stem cell; metabolic activity; metabolism; mitochondrial; osteogenesis.
© 2022 The Authors. Cell Proliferation published by John Wiley & Sons Ltd.