Klotho, a protein counteracting aging, is a powerful inhibitor of 1,25(OH)2D3 formation and regulator of mineral metabolism. In klotho-hypomorphic mice (kl/kl) excessive 1,25(OH)2D3 formation leads to hypercalcemia, hyperphosphatemia and vascular calcification, severe growth deficit, accelerated aging and early death. The kl/kl mice further suffer from extracellular volume depletion and hypotension, leading to stimulation of ADH and aldosterone release. Vitamin-D-deficient diet, restriction of dietary phosphate, inhibition of mineralocorticoid receptors with spironolactone and dietary NaCl all extend the life span of kl/kl mice. Kl/kl mice suffer from acidosis. The present study explored whether replacement of tap drinking water by 150 mM NaHCO3 affects growth, tissue calcification and life span of kl/kl mice. As a result, NaHCO3 administration to kl/kl mice did not reverse the growth deficit but substantially decreased tissue calcification and significantly increased the average life span from 78 days to 127 days. NaHCO3 did not significantly affect plasma concentrations of 1,25(OH)2D3 and Ca2+, but significantly decreased plasma phosphate concentration and plasma aldosterone concentration. The present study reveals a novel effect of bicarbonate, i.e. a favorable influence on vascular calcification and early death of klotho-deficient mice.