Despite NRF2 activation, in 18-month-old mice, klotho is further downregulated, NRF2 activation impaired, and pro-fibrotic gene expression and collagen deposition highly increased, in line with the role of klotho in diminishing cellular senescence and renal fibrosis, the hallmark of CKD [75]. Here, NFE2L2 is linked to renal fibrosis.