Low glucose conditions can enhance the proliferation of neural stem cells (NSCs) and promote neurogenesis in mice, according to new research. NSCs form neurospheres in culture, the size and number of which are indicative of NSC proliferation. Twice as many neurospheres formed in low glucose conditions than in high glucose conditions. These neurospheres also expressed increased levels of Hes-1, a marker of differentiated NSCs. As CREB and Sirtuin 1 (Sirt1) are involved in nutrient sensing, the investigators hypothesised that these proteins might regulate NSC proliferation. In low glucose conditions, CREB displaces Sirt1 from the Hes-1 promoter, which leads to increased expression of Hes-1 and consequently NSC proliferation. Conversely, in high glucose conditions, Sirt1 occupies the promoter and prevents transcription of Hes-1. Interestingly, the team found that in calorie-restricted mice, this 'molecular switch' is activated in hippocampal cells, which increases Hes-1 expression. These results suggest that in states of nutrient excess NSC renewal might be impaired.