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Airspace Enlargement With Airway Cell Apoptosis in Klotho Mice: A Model of Aging Lung

Department of Geriatric Medicine, Graduate School of Medicine, The University of Tokyo, Japan.

Address correspondence to Yasuhiro Yamaguchi, MD, Department of Geriatric Medicine, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan, 113-8655. E-mail: yamayasu-tky{at}umin.ac.jp

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.

Key Words: Klotho mouse • Aging lung • Airspace enlargement • Apoptosis • emphysema