American Journal of Physiology Lung Cellular and Molecular Physiology · Apr 30, 2026

Age-related changes in respiratory system mechanics and lung morphometry

By Decker S, Khurram OU, Mantilla CB et al.

Aging leads to degenerative changes in lung structural and mechanical properties that may impact breathing. Relatively little is known about how age-related alterations in lung mechanical properties impact expiratory duration (TE) and residual volume (RV). The present study tested three hypotheses: 1) alveolar airspace increases with age due to alveolar wall breakdown, 2) lung elastic recoil decreases, slowing expiratory flow (E-flow), and 3) airway compliance (Caw) decreases, promoting air trapping reflected by increased RV. To test these hypotheses, we evaluated changes in alveolar size using histological assessments, mechanical properties using forced oscillation perturbations with a programmable mechanical ventilator and breathing parameters using plethysmography in young (6 mo) and old (24 mo) Fischer 344 rats. Mean linear intercept (Lm) was higher in old (65 ± 10 µm) compared with young (55 ± 5 µm) rats, indicating alveolar airspace increase. In old rats, decreased elastic recoil was indicated by increased parameter K (0.178 ± 0.010 vs. 0.167 ± 0.013 in young) and higher V₁₀/total lung capacity (TLC) (80.7 ± 1.2% vs. 78.5 ± 2.5% in young). In addition, RV was higher in old rats (0.41 ± 0.10 mL vs. 0.27 ± 0.05 mL in young), consistent with air trapping. These mechanical changes were associated with increased E-flow (∼30%) in old rats, attributable to increased tidal volume (2.08 ± 0.41 mL vs. 1.53 ± 0.36 mL in young) as TE was unchanged. These results indicate important changes in the lung parenchyma, causing alteration in passive and active properties of the respiratory system in aging rats.NEW & NOTEWORTHY The present study provides novel physiological insights into aging by measuring airway compliance and residual volume via forced oscillation perturbations using a programmable mechanical ventilator (flexiVent-currently considered a gold standard for in vivo lung function measurements). In addition, dynamic measurements of lung inflation reported herein may serve as early indicators of altered elastic properties. Taken together, the findings offer a comprehensive assessment of age-related changes in lung structure and function.

doi.org/10.1152/ajplung.00341.2025PubMed 42060377Mechanisms

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