Specific ablation of Nampt in adult neural stem cells recapitulates their functional defects during aging

Neural stem/progenitor cell ( NSPC ) proliferation and self‐renewal, as well as insult‐induced differentiation, decrease markedly with age. The molecular mechanisms responsible for these declines remain unclear. Here, we show that levels of NAD + and nicotinamide phosphoribosyltransferase ( N ampt), the rate‐limiting enzyme in mammalian NAD + biosynthesis, decrease with age in the hippocampus. Ablation of Nampt in adult NSPC s reduced their pool and proliferation in vivo . The decrease in the NSPC pool during aging can be rescued by enhancing hippocampal NAD + levels. Nampt is the main source of NSPC NAD + levels and required for G 1/ S progression of the NSPC cell cycle. Nampt is also critical in oligodendrocytic lineage fate decisions through a mechanism mediated redundantly by S irt1 and S irt2. Ablation of Nampt in the adult NSPC s in vivo reduced NSPC ‐mediated oligodendrogenesis upon insult. These phenotypes recapitulate defects in NSPC s during aging, giving rise to the possibility that Nampt‐mediated NAD + biosynthesis is a mediator of age‐associated functional declines in NSPC s.