• Identified six hub genes (TBX15, IGF1, GATA2, PITX2, SNAI1, VCAN) as potential biomarkers for aging diagnosis of MSCs from aged donors.
• MSCs from aged donors exhibit differential gene expression profiles that may impair function and increase malignancy risk.
• Bioinformatics analysis of GEO datasets (GSE39035, GSE97311) combined with experimental validation in senescent MSCs confirms the findings.
• Provides a diagnostic basis for safe clinical use of MSCs and insights into rejuvenation strategies.