Bicarbonate-sensitive calcification and lifespan of klotho-deficient mice

Area of Science:

• Biochemistry
• Gerontology
• Mineral Metabolism

Background:

• Klotho protein deficiency (kl/kl mice) causes excessive 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] production, leading to hypercalcemia, hyperphosphatemia, vascular calcification, and premature aging.
• Klotho deficiency also results in extracellular volume depletion, hypotension, and acidosis, conditions that can be partially ameliorated by dietary interventions and mineralocorticoid receptor antagonists.

Purpose of the Study:

• To investigate the effects of sodium bicarbonate (NaHCO3) administration on growth, tissue calcification, and lifespan in klotho hypomorphic (kl/kl) mice.
• To explore the impact of NaHCO3 on mineral metabolism, hormone levels, and acidosis in the context of klotho deficiency.

Main Methods:

• Klotho hypomorphic (kl/kl) mice were administered 150 mM NaHCO3 in their drinking water.
• Measurements included growth parameters, tissue calcification, plasma concentrations of 1,25(OH)2D3, calcium (Ca2+), phosphate, and aldosterone.
• Lifespan was monitored to determine the effect of NaHCO3 treatment.

Main Results:

• NaHCO3 administration did not reverse growth deficits but significantly decreased tissue calcification.
• Average lifespan of kl/kl mice increased from 78 to 127 days with NaHCO3 treatment.
• Plasma phosphate and aldosterone concentrations were significantly decreased by NaHCO3, while 1,25(OH)2D3 and Ca2+ levels remained largely unaffected.

Conclusions:

• Sodium bicarbonate supplementation favorably influences vascular calcification and extends lifespan in klotho-deficient mice.
• Bicarbonate may counteract negative effects of acidosis and mineral imbalances associated with klotho deficiency.
• This study highlights a novel therapeutic potential of bicarbonate in aging and mineral metabolism disorders.