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. Author manuscript; available in PMC: 2024 Nov 4.
Published in final edited form as: Nat Aging. 2023 May 25;3(7):846–865. doi: 10.1038/s43587-023-00420-2

Fig. 3 |. Senescent Znrf3-cKO adrenal glands develop a functional SASP.

Fig. 3 |

URA using bulk RNA-seq data predicts significantly activated and inhibited cytokines in adrenal tissue from Znrf3-cKO animals at 9 weeks (a) and 12 weeks (b) compared to 6 weeks. Data are representative of four biological replicates per group. Statistical analysis in IPA was performed using a right-tailed Fisher’s exact test (P < 0.05). c,d, GSEA for inflammatory signatures (IL-6–Janus kinase ( JAK)–signal transducer and activator of transcription 3 (STAT3) signaling, chemokine signaling, the inflammatory response and the innate immune system) identifies positively enriched pathways in adrenal tissue from Znrf3-cKO animals at 9 weeks (c) and 12 weeks (d) compared to 6 weeks. FDR, false discovery rate; NES, normalized enrichment score. e, Heatmap representing supervised hierarchical clustering of the 40 most significant DEGs that encode secreted proteins compared to controls; statistical analysis was performed using the Wald test (Padj < 0.05). f,g, Histological evaluation of adrenal tissue from female control and Znrf3-cKO animals based on H&E staining. Female Znrf3-cKO animals accumulate histiocytes (inset) between 12 and 24 weeks (wk) of age. h,i, Histiocytes (insets) accumulate earlier and occupy a larger proportion of the adrenal gland in male Znrf3-cKO animals than in female animals. Quantification was performed using QuPath digital analysis based on the proportion of histiocyte area normalized to the total adrenal cortex area. Scale bars, 100 μm.