Exogenous NAD+ Postpones the D-Gal-Induced Senescence of Bone Marrow-Derived Mesenchymal Stem Cells via Sirt1 Signaling

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-beta-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.

Automated summary

Exogenous NAD(+) delays BMSC senescence induced by D-gal by increasing Sirt1 expression, reducing senescence-associated-beta-galactosidase activity, and downregulating poly (ADP-ribose) polymerase 1 expression.