Fig. 2.

(A) Summary of proposed mechanism. The net effects of klotho, typically considered a tumour suppressor, on CRC risk may be complex. Klotho represses basal Wnt activity and thus may lower neoplastic progression. On the other hand, klotho may inhibit butyrate-mediated Wnt hyperactivation, interfering with the chemopreventive action of butyrate. The relative effects of klotho on suppression of basal Wnt activity versus suppression of Wnt hyperactivation may depend on which variant of klotho is present. (B) Possible therapeutic approaches against klotho activity that can influence age-related CRC risk. Up and down solid arrows represent up-regulation and down-regulation, respectively.