Late Breaking Abstract - Aging impairs alveolar epithelial type II cell function in acute lung injury

Abstract

In the elderly, morbidity and mortality rates in acute lung injury (ALI) increase. Alveolar epithelial type II cells (AE2) are crucial for lung function and repair, but little is known about their impact on the development of ALI with age. Here we investigated functional changes in AE2 in young (12 week) and old (18 month) mice, focusing on surfactant metabolism, cell senescence and regeneration in ALI. ALI was induced with 2.5μg lipopolysaccharide (LPS)/g body weight (n=10/group). Control mice (n=7/group) received saline. Lung function was tested 24h, 72h and 10d later. With stereology and immunohistochemistry, density, total number as well as apoptotic and proliferating AE2 were quantified. Ultrastructural changes in AE2 were analyzed with electron microscopy. AE2 were further isolated from ALI and control mice and analyzed for cell senescence and changes in surfactant metabolism. Mortality rate and impairment in lung function were significantly elevated in old mice. In young mice, numerical density of AE2 was 26% higher. AE2 of young mice reacted to ALI by increasing volume and size of lamellar bodies and proliferation at day 3, which was limited in old mice. In AE2 of old mice gene expression of surfactant proteins and surfactant metabolism were significantly reduced with ALI. Cell senescence, telomere shortening or DNA damage were not apparent in AE2 of old control mice, but significantly increased with ALI (p21, p53, γH2AX). Results show impaired AE2 function in ALI of old mice with implications on lung function and repair. Even if no signs of cell aging were apparent in old control mice, AE2 were less adaptive to injury, supporting a worse pathology and limited survival in ALI with advancing age.