the mechanism of action of klotho is not fully understood, but it changes cellular calcium homeostasis, by both increasing the expression and activity of trpv5 and decreasing that of trpc6. additionally, klotho increases membrane expression of the inward rectifier channel romk. klotho-deficient mice show increased production of vitamin d, and altered mineral-ion homeostasis is suggested to be a cause of premature aging‑like phenotypes, because the lowering of vitamin d activity by dietary restriction reverses the premature aging‑like phenotypes and prolongs survival in these mutants. these results suggest that aging‑like phenotypes were due to klotho-associated vitamin d metabolic abnormalities (hypervitaminosis).