Similar to the NRF2 system, klotho is repressed in CKD, and stimulation of klotho can ameliorate oxidative stress and mitochondrial function [108], renal fibrosis [152], inflammation [72], as well as premature ageing [108], including EVA [55,81,82,83,111,112,113]. This evidence concerns the gene NFE2L2 and chronic kidney disease.