Normal Aging of the Lung

Pinkerton, Kent E.; Herring, Matt J.; Hyde, Dallas M.; Green, Francis H. Y.

doi:10.1016/b978-0-12-799941-8.00014-6

Cited by 11 publications

(6 citation statements)

References 43 publications

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“…Alternatively, one could consider using older mice because their lung biomarkers are less likely to change significantly from week to week. Yet, data on normal mouse lung development beyond the time frame of this study is scarce ( Martorana et al, 1989 ; Pinkerton et al, 2014 ) and in vivo studies are lacking. Notwithstanding that, in more mature animals, the age-associated changes might become less pronounced, in particular when compared to more substantial disease-related changes.…”

Section: Discussionmentioning

confidence: 99%

Longitudinal micro-CT provides biomarkers of lung disease that can be used to assess the effect of therapy in preclinical mouse models, and reveal compensatory changes in lung volume

Velde

Poelmans

Langhe³

et al. 2016

Disease Models &Amp; Mechanisms

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In vivo lung micro-computed tomography (micro-CT) is being increasingly embraced in pulmonary research because it provides longitudinal information on dynamic disease processes in a field in which ex vivo assessment of experimental disease models is still the gold standard. To optimize the quantitative monitoring of progression and therapy of lung diseases, we evaluated longitudinal changes in four different micro-CT-derived biomarkers [aerated lung volume, lung tissue (including lesions) volume, total lung volume and mean lung density], describing normal development, lung infections, inflammation, fibrosis and therapy. Free-breathing mice underwent micro-CT before and repeatedly after induction of lung disease (bleomycin-induced fibrosis, invasive pulmonary aspergillosis, pulmonary cryptococcosis) and therapy (imatinib). The four lung biomarkers were quantified. After the last time point, we performed pulmonary function tests and isolated the lungs for histology. None of the biomarkers remained stable during longitudinal follow-up of adult healthy mouse lungs, implying that biomarkers should be compared with age-matched controls upon intervention. Early inflammation and progressive fibrosis led to a substantial increase in total lung volume, which affects the interpretation of aerated lung volume, tissue volume and mean lung density measures. Upon treatment of fibrotic lung disease, the improvement in aerated lung volume and function was not accompanied by a normalization of the increased total lung volume. Significantly enlarged lungs were also present in models of rapidly and slowly progressing lung infections. The data suggest that total lung volume changes could partly reflect a compensatory mechanism that occurs during disease progression in mice. Our findings underscore the importance of quantifying total lung volume in addition to aerated lung or lesion volumes to accurately document growth and potential compensatory mechanisms in mouse models of lung disease, in order to fully describe and understand dynamic processes during lung disease onset, progression and therapy. This is highly relevant for the translation of therapy evaluation results from preclinical studies to human patients.

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Section: Discussionmentioning

confidence: 99%

Longitudinal micro-CT provides biomarkers of lung disease that can be used to assess the effect of therapy in preclinical mouse models, and reveal compensatory changes in lung volume

Velde

Poelmans

Langhe³

et al. 2016

Disease Models &Amp; Mechanisms

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“…This arrangement, in the form of alveoli, interfaces an air surface to a blood surface of similar proportions separated by a thin tissue barrier ( Figure 2) A review by Pinkerton and colleagues (Pinkerton et al, 2015) provides further details. With large differences in lung size among mammalian species (Table 1), it would follow that alveolar size may vary from species to species.…”

Section: Organization Of the Gas Exchange Region Of The Lungsmentioning

confidence: 97%

“…The allometric relationship of body mass to a number of parenchymal lung values listed in Table 1 (Burri, 1974;Burri et al, 1974;Pinkerton et al, 1982;Pinkerton et al, 2015). Magnification 40Â.…”

Section: Organization Of the Gas Exchange Region Of The Lungsmentioning

confidence: 98%

Architecture and Cellular Composition of the Air–Blood Tissue Barrier

Pinkerton¹,

Gehr²,

Castañeda³

et al. 2015

Comparative Biology of the Normal Lung

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“…Lung aging is accompanied by functional, micromechanical and structural alterations (Chan and Welsh, 1998; Sharma and Goodwin, 2006; Pinkerton et al, 2014). In the elderly (>65 years of age), lung diseases like chronic obstructive pulmonary disease (COPD; Ito and Barnes, 2009; Provinciali et al, 2011), fibrosis/IPF (Raghu et al, 2006; Collard, 2010; Fell et al, 2010; Thannickal, 2013), cancer (Howlader et al, 2019) or acute respiratory distress syndrome (ARDS; Ely et al, 2002; Rubenfeld et al, 2005) occur more frequently and with greater severity than in younger individuals.…”

Section: Introductionmentioning

confidence: 99%

Age-Related Structural and Functional Changes in the Mouse Lung

2019

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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.

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Normal Aging of the Lung

Cited by 11 publications

References 43 publications

Longitudinal micro-CT provides biomarkers of lung disease that can be used to assess the effect of therapy in preclinical mouse models, and reveal compensatory changes in lung volume

Longitudinal micro-CT provides biomarkers of lung disease that can be used to assess the effect of therapy in preclinical mouse models, and reveal compensatory changes in lung volume

Architecture and Cellular Composition of the Air–Blood Tissue Barrier

Age-Related Structural and Functional Changes in the Mouse Lung

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