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/).