| Abstract
| - Homozygous mutant klotho (KL−/−) mice exhibit various characteristics resembling those of human aging, including emphysema. However, age-related changes of lungs have not been fully elucidated. Here, we investigated the structural, functional, biochemical, and cell kinetic alterations of lungs in KL−/− mice at 2-12 weeks of age. Homogeneous airspace enlargement and decreased lung elastic recoil were observed in KL−/− mice with aging. The apoptotic cells in airway walls in KL−/− mice were approximately 6 times greater than those in wild-type (KL+/+) mice at 2 weeks of age. However, lipid peroxidation and elastase activity of lungs were not increased in KL−/− mice. Western blotting suggested that protein levels of epidermal growth factor (EGF) and phosphorylated extracellular signal-regulated kinase were decreased in KL−/− mice. These data suggest that significantly increased apoptosis of airway cells via inhibition of the EGF-dependent pathway may be involved in the development of the aging lungs in KL−/− mice.
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