Fig. 1: Long-term senolytic treatment prevents selective accumulation of senescent cells in physiologically aged human BOs.
From: Senolytic therapy alleviates physiological human brain aging and COVID-19 neuropathology
a–f, BOs were generated and grown in vitro for 8 months and subsequently exposed to two doses (one every 2 weeks) of either navitoclax (2.5 μM), ABT-737 (10 μM) or D + Q (D, 10 μM; Q, 25 μM) within the following month, after which organoids (n = 8–14) were collected for in situ analysis. a, SA-β-gal assay was performed on organoid sections. Each data point in the bar graph represents a single organoid analyzed. Data presented as mean ± s.d.; at least eight individual organoids were analyzed per condition; one-way analysis of variance (ANOVA) with Tukey’s multiple-comparison post hoc corrections. b, Lamin B1 staining was performed on organoid sections. Each data point in the scatter plot represents the integrated intensity of each cell within organoid sections. At least eight individual organoids were analyzed per condition; one-way ANOVA with Tukey’s multiple-comparison post hoc corrections. c,d, Representative images from quantifications shown in a,b, respectively. Scale bar, 0.3 mm. e, Representative immunofluorescent images of regions from organoids treated with the indicated senolytics and vehicle control. Samples were individually immunolabeled with antibodies against GFAP, Sox2 and NeuN and co-stained for p16. Arrows indicate coimmunoreactivity of NeuN and p16. Scale bar, 50 µm. f, Bar graphs showing colocalization quantification performed on organoid sections. Data presented as mean ± s.d.; three individual organoids were analyzed per condition; one-way ANOVA with Tukey’s multiple-comparison post hoc corrections. a.u., arbitrary units.
