Age-Related Structural and Functional Changes in the Mouse Lung.

Henri Schulte,Christina Brandenberger,Christian Mühlfeld

doi:10.3389/fphys.2019.01466

Henri Schulte, Christina Brandenberger + Show 1 more

Open Access

https://doi.org/10.3389/fphys.2019.01466

Copy DOI

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 (7.5 × 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.

Highlights

Lung aging is accompanied by functional, micromechanical and structural alterations (Chan and Welsh, 1998; Sharma and Goodwin, 2006; Pinkerton et al, 2014)
In an MRI-based study with hyperpolarized 3He gas, Quirk et al (2016) further confirmed an increase of Lm as well as decreasing alveolar depth and larger alveolar ductal radius in aging human lungs. These findings show that lung function, micromechanics and structure are closely linked and age-dependent
Body weight increased with age, showing biggest changes between young and middle-aged mice (Table 1) and Cst and inspiratory capacity (IC) per body weight remained quite stable in the course of aging (Figures 1C,D)

Summary

Introduction

Lung aging is accompanied by functional, micromechanical and structural alterations (Chan and Welsh, 1998; Sharma and Goodwin, 2006; Pinkerton et al, 2014). Investigations on age-related changes in lung micromechanics have shown that the elastic recoil pressure decreases in the elderly (Janssens et al, 1999; Turner et al, 2017), possibly due to changes in tissue composition and remodeling (Mercer and Crapo, 1990; Toshima et al, 2004; Subramaniam et al, 2017). In an MRI-based study with hyperpolarized 3He gas, Quirk et al (2016) further confirmed an increase of Lm as well as decreasing alveolar depth and larger alveolar ductal radius in aging human lungs. These findings show that lung function, micromechanics and structure are closely linked and age-dependent. Studies investigating lung aging are frequently performed under controlled laboratory conditions in animal models to correlate functional and structural parameters in the lung (Zosky, 2015)

Objectives

Methods

Results

Discussion

Conclusion