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Aging-Related Changes in Respiratory System Mechanics and Morphometry in Mice

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AJP Lung Cellular and Molecular Physiology

Published online on

Abstract

Previous work investigating respiratory system mechanics in mice has reported an aging-related increase in compliance and mean linear intercept (Lm). However, these changes were assessed using only a young (2-month-old) and old (20- and 26-month-old) group yet were interpreted to reflect a linear evolution across the lifespan. Therefore, to investigate respiratory system mechanics and lung morphometry across a more complete spectrum of ages, we utilized 2- (100% survival, n=6), 6- (100% survival, n=12), 18- (90% survival, n=12), 24- (75% survival, n=12), and 30- (25% survival, n=12) month-old C57BL/6 mice. We found a non-linear aging-related decrease in respiratory system resistance and increase in dynamic compliance and hysteresis between 2- and 24-month-old mice. However, in 30-month-old mice, respiratory system resistance increased, and dynamic compliance and hysteresis decreased relative to 24-month-old mice. Respiratory system impedance spectra were measured between 1-20.5 Hz at positive end-expiratory pressures (PEEP) of 1, 3, 5, and 7 cmH2O. Respiratory system resistance and reactance at each level of PEEP were increased and decreased, respectively, only in 2-month-old animals. No differences in the respiratory system impedance spectra were observed in 6-, 18-, 24-, and 30-month-old mice. Additionally, lungs were fixed following tracheal instillation of 4% paraformaldehyde at 25 cmH2O and processed for Lm and airway collagen deposition. There was an aging-related increase in Lm consistent with emphysematous-like changes and no evidence of increased airway collagen deposition. Accordingly, we demonstrate non-linear aging-related changes in lung mechanics and morphometry in C57BL/6 mice.