The proinflammatory cytokines TNF-α and TNF-like weak inducer of apoptosis, in addition to causing and accelerating inflammatory injury, down-regulate Klotho expression by promoting RelA binding to the Klotho promoter and inducing its deacetylation, resulting in ageing, end stage renal disease, frailty, and other age-related diseases [86, 92]. This evidence concerns the gene KL and stage 5 chronic kidney disease.