This research used CRISPR–Cas9 screening in mice to identify genes that regulate the activation of neural stem cells (NSCs) during ageing. They discovered several gene knockouts, particularly those involved in cilium organisation and glucose import, that could restore the function of old NSCs both in vitro and in vivo. Notably, the knockout of Slc2a4 (GLUT4), a glucose transporter, significantly improved NSC activation and the production of new neurons in older brains. The study found that glucose uptake increases in NSCs with age, and reducing this uptake, either genetically or through starvation, could rejuvenate old NSCs. This work establishes valuable screening platforms for uncovering genetic interventions to counter age-related regenerative decline in the brain.
Research paper:
Ruetz, T.J., Pogson, A.N., Kashiwagi, C.M. et al. CRISPR–Cas9 screens reveal regulators of ageing in neural stem cells. Nature 634, 1150–1159 (2024).
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