Extended Data Fig. 1: Changes in cell proliferation and survival with running or runner plasma infusions.

a, Male mice at 3-4 months of age had access to a running wheel for 3, 7, 14 or 28 days while controls remain without access to running wheels. EdU was administered 24 h before sacrifice. Plots show total number of cells per dentate gyrus (DG) of fluorescent immunolabelled EdU⁺ cells (n = 6-8 per group) and DCX⁺ cells (n = 6-7 per group). b, Running distance per day by male mice (n = 5) at 3-4 months of age with free access to a running wheel. c, Male mice at 3, 6, 9, 12 and 15 months of age had access to a running wheel for 28 days. Graphs show total number of DCX⁺ cells per dentate gyrus (n=4-8 per group). Means ± s.e.m; unpaired Student’s two-tailed t test; * P < 0.05, ** P < 0.01, *** P < 0.01. d, Male mice at 3 months of age had access to a running wheel for 28 days. BrdU was administered 3 days before the exercise and EdU 24 h before sacrifice. Graphs show total number of cells per dentate gyrus (DG) of fluorescent immunolabelled cells (n=4-6 per group). Means ± s.e.m; unpaired Student’s two-tailed t test; * P < 0.05. e, Control injections of saline via retro-orbital vein in combination with Isoflurane do not impair neural stem activity. Mice at 3-4 months of age were injected with saline via the tail vein or the retro orbital vein with 200 µl of saline, every 3 days for 28 days. BrdU was administered 3 days before saline administration and EdU 24 h before sacrifice. The hippocampus was dissected and processed for immunohistochemistry. Graphs show total number of cells per dentate gyrus (DG) of fluorescent immunolabelled cells (n=7-8 per group). Means ± s.e.m; Unpaired Student’s two-tailed t test. f, Runner plasma infusions from 28 days runners upregulate proliferation and survival of hippocampal new born cells. Plasma from running mice (3-4 months of age) that run for 7, 14 or 28 days was collected and transferred to matched aged non-running mice, once every 3 days 28 days. BrdU was administered 3 days before plasma administration and EdU 24 h before sacrifice. Graphs show fold change of total number of cells per dentate gyrus (DG) of fluorescent immunolabelled EdU⁺ cells, BrdU⁺ cells and DCX⁺ cells (n = 6-9 per group). Means ± s.e.m; unpaired Student’s two-tailed t test; * P < 0.05, ** P < 0.01 and *** P < 0.001. The images in a, c, d and e were generated using Servier Medical Art (https://smart.servier.com) and MediaLab (https://medialab.biochem.wisc.edu/clip-art/).