Identification and verification of biomarkers related to senescence-associated secretory phenotype in type 2 diabetes

This study aimed to identify senescence-associated secretory phenotype (SASP)-related biomarkers in type 2 diabetes (T2DM) and investigate their biological functions. SASP-related genes (SASP-RGs) were collected from literature, and differentially expressed genes (DEGs) were obtained from datasets GSE15932 and GSE21321. Candidate genes were selected by intersecting DEGs with SASP-RGs, followed by machine learning and expression level analysis to identify potential biomarkers. Functional enrichment analysis, regulatory network prediction, and immune infiltration analysis were conducted to explore the predictive capacity and regulatory pathways of these biomarkers. Blood samples from 5 T2DM patients and 5 healthy individuals were collected for PCR detection. Seven candidate genes were identified, with CCL8 significantly downregulated and MMP9 upregulated in T2DM. Functional analysis revealed that SASP-related biomarkers might play a role in T2DM pathogenesis via pathways like "e2f targets" and "interferon gamma response." Regulatory elements such as MYB and hsa-miR-181-5b, along with immune cells like mast cells, activated CD4 + T cells, and macrophages, were potentially involved in modulating these biomarkers. RT-qPCR results confirmed elevated levels of CCL8 and MMP9 in T2DM patients' blood.