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Specific ablation of Nampt in adult neural stem cells recapitulates their functional defects during aging
Author(s) -
Stein Liana R,
Imai Shinichiro
Publication year - 2014
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1002/embj.201386917
Subject(s) - biology , ablation , neural stem cell , stem cell , microbiology and biotechnology , neuroscience , medicine
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.