Continuous neurogenesis in the adult hippocampus is achieved by a tightly regulated balance between adult neural stem cell (aNSCs) self-renewal and differentiation. aNSC self-renewal is maintained by the action of ‘stemness’ genes, including Notch. Conversely, aNSC differentiation involves both the inactivation of the ‘stemness’ genes and activation of pro-neural genes. Adult hippocampal neurogenesis is regulated by intrinsic stimuli such as epigenetic modifications, as well as extrinsic inputs such as exercise, diet or hypoxia, which ultimately cause metabolic stress. However, the molecular mechanisms linking metabolic changes to the epigenetic control of aNSCs remain unclear. Using genetic ablation and pharmacological manipulation in mouse (p. ), Mu-ming Poo and co-workers show that SIRT1, a NAD+ dependent histone deacetylase and known metabolic sensor, inhibits aNSC self-renewal both in vivo and in vitro by suppressing Notch signalling in a cell-autonomous manner. Furthermore, the authors show that SIRT1 mediates the effect of metabolic stress induced by glucose restriction on aNSCs proliferation in vitro. Altogether, these results uncover a molecular mediator of the metabolic regulation of adult neurogenesis, opening the door to a better understanding and potential manipulation of adult neurogenesis.
