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The klotho mouse is an animal model that prematurely shows phenotypes resembling human aging. Here we report that in homozygotes for the klotho mutation (kl ؊/؊ ), ␣ II -spectrin is highly cleaved, even before the occurrence of aging symptoms such as calcification and arteriosclerosis. Because ␣ II -spectrin is susceptible to proteolysis by calpain, we examined the activation of calpain in kl ؊/؊ mice. m-Calpain was not activated, but -calpain was activated at an abnormally high level, and andoi:10.1074/jbc.m206033200 pmid:12119304 fatcat:vunys7t7kjdqrlstjh4gdcnnhi