The number of p16INK4A+ and p21cip1+ (cyclin-dependent kinase inhibitors 2A and 1A, respectively) beta cells (with colocalised insulin staining), indicative of senescence, was significantly increased in both older donors and donors with type 2 diabetes (Fig. 4c, d and ESM Fig. 1). This evidence concerns the gene INS and type 2 diabetes mellitus.