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. 2019 Dec 4:10:1466.
doi: 10.3389/fphys.2019.01466. eCollection 2019.

Age-Related Structural and Functional Changes in the Mouse Lung

Henri Schulte  1 , Christian Mühlfeld  1   2   3 , Christina Brandenberger  1   2   3
Affiliations

Age-Related Structural and Functional Changes in the Mouse Lung

Henri Schulte (VSports注册入口) et al. Front Physiol. .

Abstract

Lung function declines with advancing age. To improve our understanding of the structure-function relationships leading to this decline, we investigated structural alterations in the lung and their impact on micromechanics and lung function in the aging mouse. Lung function analysis was performed in 3, 6, 12, 18, and 24 months old C57BL/6 mice (n = 7-8/age), followed by lung fixation and stereological sample preparation. Lung parenchymal volume, total, ductal and alveolar airspace volume, alveolar volume and number, septal volume, septal surface area and thickness were quantified by stereology as well as surfactant producing alveolar epithelial type II (ATII) cell volume and number. Parenchymal volume, total and ductal airspace volume increased in old (18 and 24 months) compared with middle-aged (6 and 12 months) and young (3 months) mice. While the alveolar number decreased from young (7 VSports手机版. 5 × 106) to middle-aged (6 × 106) and increased again in old (9 × 106) mice, the mean alveolar volume and mean septal surface area per alveolus conversely first increased in middle-aged and then declined in old mice. The ATII cell number increased from middle-aged (8. 8 × 106) to old (11. 8 × 106) mice, along with the alveolar number, resulting in a constant ratio of ATII cells per alveolus in all age groups (1. 4 ATII cells per alveolus). Lung compliance and inspiratory capacity increased, whereas tissue elastance and tissue resistance decreased with age, showing greatest changes between young and middle-aged mice. In conclusion, alveolar size declined significantly in old mice concomitant with a widening of alveolar ducts and late alveolarization. These changes may partly explain the functional alterations during aging. Interestingly, despite age-related lung remodeling, the number of ATII cells per alveolus showed a tightly controlled relation in all age groups. .

Keywords: alveolar epithelial type II cells; late alveolarization; micromechanics; pulmonary aging; stereology V体育安卓版. .

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Figures (V体育官网)

FIGURE 1
FIGURE 1
Lung function and micromechanics. Inspiratory capacity (IC) (A) and static compliance (Cst) (B) showed significant increases from young to middle-aged and old mice, respectively. However, IC and Cst corrected for body weight remained rather constant over lifetime (C,D). Tissue resistance (G) (E) and tissue elastance (H) (F) changed most in early mouse adulthood. Hysteresivity (η) remained constant during aging (G), whereas hysteresis increased from 3 and 6 mo mice to 18 mo mice (H). Each point represents one animal; bars show means and lines indicate statistically significant differences between age groups (one-way ANOVA with Bonferroni t-test, p < 0.05).
FIGURE 2
FIGURE 2
Lung parenchymal airspace volumes. (A–E) Representative light micrographs of each age group stained with toluidine blue show pulmonary histology. No inflammation or fibrosis was observed qualitatively at any time point. The light micrographs of 3 (A), 6 (B), and 12 (C) mo mice show a compact, regular lung parenchyma, whereas the light micrographs of 18 (D) and 24 (E) mo mice reveal visible widening of alveolar ducts causing a less compact appearance of the parenchyma. Scale bar = 100 μm. (F–J) Graphs show lung volume (F) and stereological results of parenchymal volume (G), total parenchymal airspace volume (H), ductal airspace volume (I), and alveolar airspace volume (J). Each point represents one animal; bars show means and lines indicate statistically significant differences between age groups (one-way ANOVA with Bonferroni t-test, p < 0.05).
FIGURE 3
FIGURE 3
Alveolar changes with age. (A–E) Representative light micrographs of each age group show pulmonary histology of eosin-orcein stained lungs. Arrowheads indicate alveolar septal border tips as part of the alveolar entrance ring. Septal border tips are dyed brown by orcein, demonstrating elastin accumulation around the alveolar entrances. Alveolar ducts are indicated by “d.” At 3 months (A), a high density of small alveoli and narrow alveolar ducts can be observed. The light micrographs of 6 (B) and 12 (C) mo mice show similar narrow alveolar ducts, but alveoli appear less dense. In 18 (D) and 24 (E) mo mice, the alveolar density seems to remain constant compared to middle-aged mice. The alveolar ducts, however, appear wider and alveolar septal borders seem to be shorter. Scale bar = 50 μm. (F–J) Graphs show stereological results of alveolar number density (F), alveolar number (G), total alveolar septal surface area (H), mean septal surface area per alveolus (I), and mean alveolar volume (J). Each point represents one animal; bars show means and lines indicate statistically significant differences between age groups (one-way ANOVA with Bonferroni t-test, p < 0.05).
FIGURE 4
FIGURE 4
Alveolar epithelial type II (ATII) cell characteristics. (A–E) Representative light micrographs of each age group show pulmonary histology. Tissue sections were stained with toluidine blue. Arrowheads indicate ATII cells, typically located in alveolar “corners”. Intracellular lamellar bodies appear violet due to a metachromatic staining behavior. The ATII cells look quite homogeneous at any age in light microscopic images. However, the cell number density seems to be highest in 3 mo mice (A). Scale bar = 20 μm. (F–J) Graphs show stereological results of ATII cell number density (F) and ATII cell number (G) as well as mean ATII cell number per alveolus (H), mean ATII cell number per alveolar septal surface area (I), and mean ATII cell volume (J). Each point represents one animal; bars show means and lines indicate statistically significant differences between age groups (one-way ANOVA with Bonferroni t-test, p < 0.05).
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