More specifically, the proportion of p16INK4a-positive cells was found to decrease in the NP tissue sections of the butein-treated diabetic IDD rats compared with the diabetic IDD rats in the absence of butein, in parallel to the noticeable observed up-regulation of SIRT1 and down-regulation of acetylated p53. The gene discussed is CDKN2A; the disease is intervertebral disk degenerative disorder.