Age-Related Structural and Functional Changes in the Mouse Lung
Age-Related Structural and Functional Changes in the Mouse Lung
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DOI：
10.3389/fphys.2019.01466
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发表时间：
2019-12-04
影响因子：
4
通讯作者：
Brandenberger, Christina
中科院分区：
文献类型：
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作者：
Schulte, Henri;Muehlfeld, Christian;Brandenberger, Christina
肺功能随着年龄的增长而下降。为了提高我们对导致这种下降的结构-功能关系的理解，我们研究了肺的结构变化及其对衰老小鼠微观力学和肺功能的影响。在3、6、12、18和24个月大的C57 BL/6小鼠（n = 7-8只/年龄）中进行肺功能分析，然后进行肺固定和体视学样品制备。通过体视学以及产生表面活性剂的肺泡上皮II型（ATII）细胞体积和数量，定量肺实质体积、总体积、导管和肺泡气容积、肺泡体积和数量、间隔体积、间隔表面积和厚度。与中年（6个月和12个月）和年轻（3个月）小鼠相比，老年（18个月和24个月）小鼠的实质体积、总体积和导管空域体积增加。虽然肺泡数量从年轻（7.5 x 10（6））到中年（6 x 10（6））减少，并在老年（9 x 10（6））小鼠中再次增加，但平均肺泡体积和每个肺泡的平均间隔表面积相反地在中年小鼠中首先增加，然后在老年小鼠中下降。从中年小鼠（8.8 x 10（6））到老年小鼠（11.8 x 10（6）），ATII细胞数量随着肺泡数量的增加而增加，沿着增加，导致所有年龄组中每个肺泡的ATII细胞比例恒定（每个肺泡1.4个ATII细胞）。肺顺应性和吸气量增加，而组织弹性和组织阻力随着年龄的增长而下降，年轻和中年小鼠之间的变化最大。总之，老年小鼠肺泡大小明显下降，肺泡管变宽，肺泡化较晚。这些变化可以部分解释衰老过程中的功能改变。有趣的是，尽管存在与年龄相关的肺重塑，但每个肺泡的ATII细胞数量在所有年龄组中均显示出严格控制的关系。
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 x 10(6)) to middle-aged (6 x 10(6)) and increased again in old (9 x 10(6)) 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 x 10(6)) to old (11.8 x 10(6)) 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.