Cell senescence is accompanied by decreased nicotinamide adenine dinucleotide (NAD+) levels; however, whether exogenous NAD+ affects bone marrow-derived mesenchymal stem cells (BMSCs) senescence and the involved mechanisms is still unclear. Here, we find that exogenous NAD+ replenishment significantly postpones BMSC senescence induced by D-galactose (D-gal). It is also shown that exogenous NAD+ leads to increased intracellular NAD+ levels and reduced intracellular reactive oxygen species in senescent BMSCs here. Further investigation showed that exogenous NAD+ weakened BMSC senescence by increasing Sirtuin 1 (Sirt1) expression. Moreover, exogenous NAD+ reduced senescence-associated-β-galactosidase activity, and downregulated poly (ADP-ribose) polymerase 1 expression. In addition, the reduced expression of Sirt1 by small interfering RNA abolished the beneficial effects of exogenous NAD+ in terms of postponing BMSCs senescence induced by D-gal. Taken together, our results indicate that exogenous NAD+ could postpone D-gal-induced BMSC senescence through Sirt1 signaling, providing a potential method for obtaining high quality BMSCs to support their research and clinical application.
Keywords: mesenchymal stem cells; nicotinamide adenine dinucleotide; senescence; sirtuin 1 signaling.