Fork box O4 (Foxo4) transcription factor can be activated to promote podocyte apoptosis by AGEs through Bcl2111 expression, at the same time, AGE-BSA can also increase Foxo4 acetylation; a recent study showed that alteration of Foxo4 acetylation and downregulation of Sirt1 expression in DM promote podocyte apoptosis; Foxo4 acetylation reduction could be a therapeutic potential for preventing diabetic podocyte loss [45]. The gene discussed is SIRT1; the disease is diabetes mellitus.