Identification of senescence-related hub genes and potential therapeutic agents in chronic heart failure

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Chronic heart failure (CHF) involves persistent inflammation, maladaptive remodeling, and metabolic dysfunction, but its senescence-related molecular architecture remains poorly defined. We integrated two left-ventricular transcriptomic datasets comprising 14 CHF and 11 control samples with the CellAge resource. Differential-expression, functional-enrichment, protein-interaction, and regulatory-network analyses were used to identify senescence-related hub genes. Candidate compounds were prioritized by drug-gene enrichment, followed by exploratory molecular docking and RT-qPCR validation in a doxorubicin-induced rat model with six animals per group. We identified 47 senescence-related differentially expressed genes and nine consensus hub genes: STAT1 , MMP9 , MAP2K1 , SOCS1 , SDC1 , MET , EIF4EBP1 , ATF3 , and NAMPT . These genes were enriched in apoptotic, inflammatory, stress-response, and metabolic pathways. Each hub gene achieved an area under the curve above 0.70 within the integrated retrospective dataset, indicating preliminary discriminatory value. Metformin ranked first in the drug-gene analysis and was linked to MMP9, MET, EIF4EBP1, and NAMPT. Docking scores ranged from − 5.8 to − 5.4 kcal/mol, and myocardial expression changes in the rat model were directionally concordant with the transcriptomic results. These findings define a senescence-associated transcriptional signature in CHF and nominate testable molecular targets and candidate compounds. Independent clinical cohorts, biochemical binding assays, and mechanistic experiments are required before diagnostic or therapeutic translation. This figure was created by using BioRender.

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