Klotho is a powerful regulator of 1,25(OH)₂D₃ formation and mineral metabolism and counteracts a wide variety of age related disorders. Klotho hypomorphic mice (kl/kl) suffer from severe growth deficit, rapid aging and early death and severe soft tissue calcification. As shown earlier, kl/kl mice suffer from extracellular volume depletion and hypotension, leading to stimulation of aldosterone release. We therefore investigated the contribution of aldosterone to the phenotype of calcification in kl/kl mice. We show here that the mineralocorticoid receptor blocker spironolactone reduced tissue calcification and substantially increased life span of kl/kl mice, despite continued increase of 1,25(OH)₂D₃, Ca²⁺ and phosphate plasma concentrations. We could show that the osteoinductive axis of TNFa/NfkB/Bmp2/Msx2/Osterix/Wnt/p38 signalling, which leads to up-regulation of alkaline phosphatase and fosters vascular calcification could be reduced by spironolactone treatment in calcified tissue ofkl/kl mice. The increased expression of the osteoblastic signalling in calcified tissue indicates an active process underlying the extensive calcifications in kl/kl mice, which is mitigated by spironolactone treatment. Thus, despite of hypovolemia and hypotension, hyperaldosteronism substantially contributes to tissue calcification and rapid ageing of klotho deficient mice. The present observations may be particularly relevant for patients with chronic kidney disease, who, similar to kl/kl mice, suffer from hyperphosphatemia and vascular calcification.