Department of Biomedical Engineering, Boston University, Boston, Massachusetts, USA.
Depatment of Medicine, University of Vermont Larner College of Medicine, Burlington, Vermont, USA.
Compr Physiol. 2022 Jun 29;12(3):3559-3574. doi: 10.1002/cphy.c210033.
Aging is a slow process that affects all organs, and the lung is no exception. At the alveolar level, aging increases the airspace size with thicker and stiffer septal walls and straighter and thickened collagen and elastic fibers. This creates a microenvironment that interferes with the ability of cells in the parenchyma to maintain normal homeostasis and respond to injury. These changes also make the lung more susceptible to disease such as emphysema. Emphysema is characterized by slow but progressive remodeling of the deep alveolar regions that leads to airspace enlargement and increased but disorganized elastin and collagen deposition. This remodeling has been attributed to ongoing inflammation that involves inflammatory cells and the cytokines they produce. Cellular senescence, another consequence of aging, weakens the ability of cells to properly respond to injury, something that also occurs in emphysema. These factors conspire to make alveolar walls more prone to mechanical failure, which can set emphysema in motion by driving inflammation through immune stimulation by protein fragments. Both aging and emphysema are influenced by microenvironmental conditions such as local inflammation, chemical makeup, tissue stiffness, and mechanical stresses. Although aging and emphysema are not equivalent, they have the potential to influence each other in synergistic ways; aging sets up the conditions for emphysema to develop, while emphysema may accelerate cellular senescence and thus aging itself. This article focuses on the similarities and differences between the remodeled microenvironment of the aging and emphysematous lung, with special emphasis on the alveolar septal wall. © 2022 American Physiological Society. Compr Physiol 12:3559-3574, 2022.
衰老是一个缓慢的过程，会影响所有器官，肺部也不例外。在肺泡水平，衰老会使气腔增大，隔壁变厚、变硬，胶原和平滑肌纤维变直、变粗。这会形成一个微环境，干扰实质细胞维持正常内稳态和对损伤做出反应的能力。这些变化也使肺部更容易受到肺气肿等疾病的影响。肺气肿的特征是深肺泡区域的缓慢但进行性重塑，导致气腔增大，弹性蛋白和胶原沉积增加但无序。这种重塑归因于持续的炎症，涉及炎症细胞及其产生的细胞因子。细胞衰老，衰老的另一个后果，削弱了细胞对损伤做出适当反应的能力，这在肺气肿中也会发生。这些因素共同作用使肺泡壁更容易发生机械故障，通过免疫刺激蛋白片段驱动炎症，从而使肺气肿开始发展。衰老和肺气肿都受到微环境条件的影响，如局部炎症、化学成分、组织硬度和机械应力。虽然衰老和肺气肿并不等同，但它们有可能以协同的方式相互影响；衰老为肺气肿的发展创造了条件，而肺气肿可能会加速细胞衰老，从而加速衰老本身。本文重点讨论了衰老和肺气肿肺部重塑微环境之间的相似和不同之处，特别强调了肺泡隔壁。© 2022 美国生理学会。综合生理学 12:3559-3574, 2022。
