Fig. 7: Treatment with TrkB inhibitors reduces senescent cells in organs from old mice.

a Immunofluorescence staining of BDNF (green) and p16 (red) in kidney, lung, and liver from 24-month old (m.o.) C57BL/6 J mice. Scale bars, 20 µm. The percentages of double p16- and BDNF-positive cells among the total p16-positive cells were analyzed (n = 5 mice, 24 m.o.) and plotted (right). b Schedule of administration of TrkB inhibitors GNF 5837 and PF 06273340 to normally aging mice. Groups included are Y (young, 3 m.o.) and O (old, 24 m.o.); - (untreated), GNF (GNF 5837), and PF (PF 06273340). Created using BioRender. c RT-qPCR analysis of the abundance of p16, p21, Il6, and Il1b mRNAs in kidney, lung, and liver in the different mouse cohorts. d GDF15 concentration in sera from the four mouse cohorts, as measured with a Bioplex instrument. Percentages of p16-positive cells in kidney, lung, and liver of the four mouse cohorts (e), and representative images of p16-positive cells in the kidney of the groups tested (f). Representative images (g) and quantification (h) of SA-β-Gal activity assessment performed in the same four mouse cohorts described in b. i Percent relative fibrotic area measured as the fraction of Sirius Red-positive area present in the images taken from n = 5 mice from each of the groups described in b. Additional data in Supplementary Fig. 7f. j Serum concentration of urea and creatinine measured in the mouse groups described in b. Scale bars in f and g, 200 µm. Data in c were normalized to Actb mRNA. Graphs in c–e, and h–j reflect individual data points; values are displayed as means ± SD; significance (*p < 0.05, **p < 0.01, ***p < 0.001) was determined by using two-tailed Student’s t-test.