Figure 9.

A schematic diagram illustrating the underlying mechanism of melatonin-mediated anti-senescence effect in OVX rats. Estrogen deficiency results in a bone loss and bone microstructure deterioration. BMMSCs derived from OVX rats (OVX BMMSCs) show that estrogen deficiency did not directly cause stem cell senescence, but exposure to low levels of oxidative stress rapidly induced premature senescence in OVX BMMSCs. Melatonin prevents oxidative stress-induced senescence in OVX BMMSCs and subsequently restores their impaired osteogenic capacity via activation of the AMPK-SIRT1 signaling pathway through melatonin receptors. Intravenous administration of melatonin ameliorates bone loss in OVX rats and preserves the anti-senescence property of BMMSCs.