Research Paper Advance Articles

Growth hormone excess drives liver aging via increased glycation stress

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Figure 1. Transcriptomic alterations in the liver of bGH-Tg mice compared to WT controls. Three-month-old bGH-Tg and WT (C57BL6J) male mice were used for this study, and liver tissues were collected at 10 months of age for bulk RNA-seq analysis. Principal component analysis (A) shows clear segregation between WT and bGH-Tg liver transcriptomes. Differential expression analysis (B) identifies 4,209 upregulated and 1,193 downregulated genes in bGH-Tg mice compared to WT controls. Pathway enrichment analysis of upregulated genes (C) reveals enrichment of cytokine–cytokine receptor interaction, cell adhesion molecules, focal adhesion, microRNAs in cancer, hematopoietic cell lineage, and ECM–receptor interaction pathways, consistent with inflammatory and immune activation. TRRUST analysis (D) implicates transcription factors including SP1, RELA, NFKB1, TP53, JUN, and STAT1 as potential regulators of these pathways. Analysis of downregulated genes (E) highlights enrichment of metabolic and detoxification pathways, including steroid hormone biosynthesis, pyruvate metabolism, bile secretion, fatty acid metabolism, PPAR signaling, oxidative phosphorylation, and xenobiotic metabolism by cytochrome P450. TRRUST analysis (F) further identifies transcription factors such as CLOCK, Srebf1, PPARA, and Hnf family members as regulators of these metabolic changes, underscoring disrupted metabolic homeostasis in bGH-Tg livers.