Figure 6.

Signature of core senescence proteins, networks and pathways in prolonged IGF1-induced senescence. Summary of proteins significantly altered (p-value < 0.05) by prolonged IGF1 treatment compared to serum starvation condition in human skin primary fibroblasts. Analyses were performed with the Perseus tool using proteins with FDR-corrected p-value less than 0.05 and log₂ fold-changes greater than 1.5. (A,B) Gene Ontology enrichment analysis of differentially expressed proteins in prolonged IGF1-treated cells. Proteins were ranked by average log₂ fold-change and analyzed by gene set enrichment analysis (GSEA). Normalized enrichment score was calculated for upregulated and downregulated pathways resulting from prolonged IGF1 treatment. (C) Volcano plot representing average log₂ (prolonged IGF1 treatment—serum starvation) fold-change in X-axis versus –log₁₀ p-value in Y-axis, combined statistical significance from three datasets. Red and green dots denote proteins that were consistently up- or downregulated, respectively, in all three datasets (FDR-corrected p-value < 0.05, average absolute log₂ fold-change > 1.5). (D) Hierarchical clustering representing a part of the cluster containing differentially expressed proteins with the smallest FDR-corrected p-value after integrating the three datasets. All independent technical replicates are shown. Note that the fold-changes presented in the figure are in logarithmic terms (log₂). Log₂ fold-change of 1.5 is equal to fold-change of 2 or (1.5)².