Exercise Increases Neural Stem Cell Number in a GH-Dependent Manner, Augmenting the Regenerative Response in Aged Mice

The exercise-induced enhancement of learning and memory, and its ability to slow age-related cognitive decline in humans led us to investigate whether running stimulates periventricular (PVR) neural stem cells (NSCs) in aging mice, thereby augmenting the regenerative capacity of the brain. To establish a benchmark of normal aging on endogenous NSCs, we harvested the PVR from serial vibratome sections through the lateral ventricles of juvenile (6-8 weeks), 6, 12, 18, and 24-month-old mice, culturing the cells in the neural colony forming cell assay. A significant decline in NSC frequency was apparent by 6-months (~40%) ultimately resulting in a ~90% reduction by 24-months. Concurrent with this decline was a progressive loss in regenerative capacity, as reflected by an incomplete repopulation of neurosphere-forming cells following gamma cell irradiation-induced depletion of the PVR. However voluntary exercise (i.e. 21 days of running) significantly increased NSC frequency in mic