Aging and Lung Disease

Abstract

People worldwide are living longer, and it is estimated that by 2050, the proportion of the world's population over 60 years of age will nearly double. Natural lung aging is associated with molecular and physiological changes that cause alterations in lung function, diminished pulmonary remodeling and regenerative capacity, and increased susceptibility to acute and chronic lung diseases. As the aging population rapidly grows, it is essential to examine how alterations in cellular function and cell-to-cell interactions of pulmonary resident cells and systemic immune cells contribute to a higher risk of increased susceptibility to infection and development of chronic diseases, such as chronic obstructive pulmonary disease and interstitial pulmonary fibrosis. This review provides an overview of physiological, structural, and cellular changes in the aging lung and immune system that facilitate the development and progression of disease.

Keywords: ARDS; COPD; IPF; acute respiratory distress syndrome; chronic obstructive pulmonary disease; inflammation; interstitial pulmonary fibrosis; lung aging; pneumonia.

Figure 1

Cellular changes in the aged lung. The epithelial surface of the respiratory airways is a large, highly vascularized area where efficient gas exchange and host defense rely on the integrity of the epithelium; age-associated changes in type I and II epithelial, fibroblast, endothelial, and airway smooth muscle cell composition and function can contribute to the development and progression of lung disorders in the elderly. Poor prognosis and recovery in pulmonary inflammatory diseases has been attributed to immunosenescence or age-related changes in innate and adaptive immune responses in the lung. Abbreviations: ECM, extracellular matrix; NET, neutrophil extracellular trap.

Figure 2

Comparison of aged and chronic obstructive pulmonary disease (COPD) lung. Many of the anatomical and physiological changes seen in COPD, such as airspace dilation resulting from loss of supporting tissue without alveolar wall destruction, have also been described in the similarly aged lungs of nonsmokers, further illustrating that the process of aging is a contributing factor for disease progression. However, when compared to aging lungs, there is a significant increase in collagen, fibronectin, and laminin, with more disorganized collagen fibers present in COPD lungs. Chronic bronchitis, with increased airway wall thickening, inflammation, and heightened mucus production as well as emphysema, with alveolar wall destruction, hyperinflation and impaired gas exchange, are two common phenotypic manifestations of COPD.

Figure 3

Cellular and molecular mechanisms that contribute to interstitial pulmonary fibrosis (IPF). In panel a, IPF is characterized by repetitive epithelial cell injury, increased alveolar epithelial cell senescence, production by profibrotic mediators contributing to elevated matrix deposition by myofibroblasts, changes in microbiome composition, and abnormalities in host immune defense. Therapeutic interventions are shown in green. In panels b (low power) and c (high power), histological features (hematoxylin and eosin staining) of usual interstitial pneumonia (UIP) are illustrated. Fibroblastic foci, a prominent, but nonspecific feature of IPF, are illustrated by an asterisk. Abbreviations: AEC, alveolar epithelial cell; CCL2, chemokine (C-C motif) ligand 2; CTGF, connective tissue growth factor; CXCL12, C-X-C motif chemokine ligand 12; FGF-2, fibroblast growth factor 2; FGFR1, fibroblast growth factor receptor 1; LOXL2, lysyl oxidase-like 2; LPA, lysophosphatidic acid; LPA₁, lysophosphatidic acid receptor type 1; LPC, lysophosphatidylcholine; MCP-1, monocyte chemoattractant protein 1; MMP, matrix metalloproteinase; PDGF, platelet-derived growth factor; PDGFR: PDGF receptor; SDF-1, stromal cell–derived factor 1; SNP, single nucleotide polymorphism; TGF-β, transforming growth factor β; TGFβR1/2, TGFβ receptor type 1 or 2; TIMP, tissue inhibitor of metalloproteinases; TRPV4, transient receptor potential cation channel subfamily V member 4; VEGF, vascular endothelial growth factor; VEGFR, VEGF receptor. Adapted with permission from Reference . Copyright 2018, Massachusetts Medical Society.