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Aging causes a slowing in ciliary beat frequency, mediated by PKC{varepsilon}

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AJP Lung Cellular and Molecular Physiology

Published online on

Abstract

The elderly are at much higher risk for developing pneumonia than younger individuals. Pneumonia is a leading cause of death and the third most common reason for hospitalization in the elderly. One reason that the elderly may be more susceptible to pneumonia is a breakdown in the lung's first line of defense, mucociliary clearance. Cilia beat in a coordinated manner to propel out invading microorganisms and particles. Ciliary beat frequency (CBF) is known to slow with aging, however little is known about the mechanism(s). We compared the CBF in BALB/c and C57BL/6 mice aged 2 months, 12 months and 24 months and found that CBF diminishes with age. Both the 12 and 24-month cilia retained their ability to be stimulated by the β2 agonist, procaterol. To help determine the mechanism of ciliary slowing, we measured PKCα and PKC activity. There were no activity differences in PKCα; however, we demonstrate a significantly higher PKC activity in the 12- and 24-month mice than the 2-month mice. The increase in activity is likely due to a nearly 3-fold increase in PKC protein in the lung during aging. To strengthen the connection between PKC activation and ciliary slowing, we treated 2-month tracheas with the PKC agonist, 8-[2-(2-pentylcyclopropylmethyl)-cyclopropyl]-octanoic acid (DCP-LA). We noted a similar decrease in baseline CBF, and the cilia remained sensitive to stimulation with β2 agonists. Conclusions: In this mouse model of aging, we show that the decreases in CBF are related to an increase in PKC activity.