• Selective clearance: Induces apoptosis specifically in senescent cells, showing potential for targeting senescence subpopulations accumulated under metabolic disorder.• SASP Inhibition: Suppresses NF-κB transactivation, downregulating TNF-α and IL-6 secretion.• Functional recovery: Restores proliferative capacity of dermal fibroblasts and angiogenic function of endothelial cells. Demonstrated superior efficacy and safety over ABT-263 in both type I and II diabetic mouse Models. Here, NFKB1 is linked to metabolic disease.