We found that clearance of p16-positive cells, most of them are senescent cells, (1) decreased senescence and the expression of the components of the senescence-associated secretory phenotypes (SASPs), (2) restored kidney adenosine triphosphate (ATP) content, (3) decreased the expression of the key glycolytic genes to improve the metabolic reprogramming, (4) normalized the mitochondrial metabolism through AMPK and mTOR pathway, resulting in an amelioration of the progression of DKD. The gene discussed is CDKN2A; the disease is diabetic kidney disease.