• PRR is upregulated in diabetic hearts and correlates with senescence markers (SA-β-gal, γ-H2AX, p16, p21).
• PRR overexpression exacerbates cardiomyocyte senescence and SASP, leading to fibrosis and cardiac dysfunction.
• Mechanistically, PRR stabilizes p53 by inhibiting TRIM24-mediated ubiquitination, activating the p53-p21 axis.
• Targeting PRR or TRIM24 may offer novel therapeutic strategies for diabetic cardiomyopathy.