Fig. 2: Transcriptomic characterization of distinct senolytic interventions on brain aging hallmarks.
From: Senolytic therapy alleviates physiological human brain aging and COVID-19 neuropathology
a–g, 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 were collected and subjected to bulk RNA-seq analysis. a–c, Volcano plots showing vehicle-treated versus navitoclax- (a), ABT-737- (b) and D + Q-treated (c) BO differential expression of upregulated (blue) and downregulated (red) mRNAs (P < 0.05, log2FC > 0). d, Venn diagram showing differentially repressed senescence-associated mRNAs among senolytic-treated organoids, defined by significance P < 0.05 and log2FC > 0. e, GSEA was carried out using aging hallmark gene sets from the Molecular Signature Database. Statistically significant signatures were selected (P < 0.05, false discovery rate < 0.25) and placed in order of NES. Bars indicate pathways enriched in individual senolytic treatments compared with vehicle-treated BOs. f, Transcriptomic age (tAge) of organoids treated with either vehicle or senolytic compounds assessed using the brain multispecies aging clock. Three individual organoids were analyzed per condition. Box-and-whisker plot (minimum, 25th percentile; median, 75th percentile; maximum). g, Spearman correlation between gene expression changes induced by senolytics in aged organoids and signatures of aging and established lifespan-extending interventions based on functional enrichment output. NES calculated with GSEA were used to evaluate correlations between pairs of signatures.
