Age-dependent changes of airway and lung parenchyma in C57BL/6J mice

Abstract

In the current study, we hypothesize that senescent-dependent changes between airway and lung parenchymal tissues of C57BL/6J (B6) mice are not synchronized with respect to altered lung mechanics. Furthermore, aging modifications in elastin fiber and collagen content of the airways and lung parenchyma are remodeling events that differ with time. To test these hypotheses, we performed quasi-static pressure-volume (PV) curves and impedance measurements of the respiratory system in 2-, 20-, and 26-mo-old B6 mice. From the PV curves, the lung volume at 30 cmH(2)O pressure (V(30)) and respiratory system compliance (Crs) were significantly (P < 0.01) increased between 2 and 20 mo of age, representing about 80-84% of the total increase that occurred between 2 and 26 mo of age. Senescent-dependent changes in tissue damping and tissue elastance were analogous to changes in V(30) and Crs; that is, a majority of the parenchymal alterations in the lung mechanics occurred between 2 and 20 mo of age. In contrast, significant decreases in airway resistance (R) occurred between 20 and 26 mo of age; that is, the decrease in R between 2 and 20 mo of age represented only 29% (P > 0.05) of total decrease occurring through 26 mo. Morphometric analysis of the elastic fiber content in lung parenchyma was significantly (P < 0.01) decreased between 2 and 20 mo of age. To the contrary, increased collagen content was significantly delayed until 26 mo of age (P < 0.01, 2 vs. 26 mo). In conclusion, our data demonstrate that senescent-dependent changes in airway and lung tissue mechanics are not synchronized in B6 mice. Moreover, the reduction in elastic fiber content with age is an early lung remodeling event, and the increased collagen content in the lung parenchyma occurs later in senescence.

The receptor for advanced glycation end-products supports lung tissue biomechanics

“…However, RAGE should have a supporting effect on the lung biomechanics as demonstrated for the lower dynamic lung compliance and better maximal expiratory air flow. The mouse airway resistance was reduced with advanced age as also observed by Huang et al (20,21), but this reduction is not significantly influenced by RAGE. Our findings are in contrast to previous observations of Ramsgaard et al (38), who did not find RAGE-dependent differences in the respiratory function.…”

“…The higher mRNA and protein expression of elastin in the lung of WT mice compared with RAGE-KO mice might explain this faster expiratory air flow but also the lower lung compliance. This inverse correlation between level of functional elastin and lung compliance was already demonstrated in elastase treatment models (24,25) and indirectly in experimental aging models (20,21). In contrast, surfactant proteins do not seem to play a pivotal role because their expression was not influenced by RAGE.…”

Assessment of morphometry of pulmonary acini in mouse lungs by nondestructive imaging using multiscale microcomputed tomography

“…The measurements thus obtained on the individual acini are given in Table S1. The mean total lung volume was significantly higher in the old mice compared with the young mice (mean, 1,398 ± 229 mm 3 vs. 959 ± 187 mm 3 ; P = 0.001) ( Table 1), possibly due in part to the greater compliance in older mice (7,11). Acinar volume was also significantly greater in the old mice (0.36 ± 0.15 mm 3 vs. 0.18 0.08 ± mm 3 ; P = 0.002).…”

Global expression profiles from C57BL/6J and DBA/2J mouse lungs to determine aging-related genes

“…In general, the choice of age categories for the present study corresponds to similar age groups used in two previous studies (23,24) from our laboratory outlining the age-dependent changes in the lung and the variation between strains. However, there may be some concern over the use of 2-mo-old mice as young controls.…”