Adult neural stem cells and neurogenesis are resilient to intermittent fasting

Intermittent fasting (IF) is a promising strategy to counteract ageing shown to increase the number of adult‐born neurons in the dentate gyrus of mice. However, it is unclear which steps of the adult neurogenesis process are regulated by IF. The number of adult neural stem cells (NSCs) decreases with age in an activation‐dependent manner and, to counteract this loss, adult NSCs are found in a quiescent state which ensures their long‐term maintenance. We aimed to determine if and how IF affects adult NSCs in the hippocampus. To identify the effects of every‐other‐day IF on NSCs and all following steps in the neurogenic lineage, we combined fasting with lineage tracing and label retention assays. We show here that IF does not affect NSC activation or maintenance and, that contrary to previous reports, IF does not increase neurogenesis. The same results are obtained regardless of strain, sex, diet length, tamoxifen administration or new‐born neuron identification method. Our data suggest that NSCs maintain homeostasis upon IF and that this intervention is not a reliable strategy to increase adult neurogenesis. Synopsis Combining genetic lineage tracing and label retention experiments, this study shows that every‐other‐day intermittent fasting does not affect adult neural stem cell behaviour and, despite previous encouraging data, is not a reliable strategy to promote adult hippocampal neurogenesis in mice. Night‐time every‐other‐day intermittent fasting elicits a systemic fasting response in mice while preserving circadian activity. Intermittent fasting has no effect on the proliferation or maintenance of adult neural stem cells in the dentate gyrus. Irrespective of the mouse strain, sex, labelling method, diet length, or refeeding protocol evaluated in this work, intermittent fasting did not promote adult hippocampal neurogenesis. Combining genetic lineage tracing and label retention experiments, this study shows that every‐other‐day intermittent fasting does not affect adult neural stem cell behaviour and, despite previous encouraging data, is not a reliable strategy to promote adult hippocampal neurogenesis in mice.