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Aging and Susceptibility to Pulmonary Disease

Julia Budde, Gwen Skloot

10.1002/cphy.c210026

Source: Volume 12, Issue 3, July 2022

Published online: June 2022

Full Article on Wiley Online Library



Abstract

The lungs are continually subjected to noxious and inert substances, are immunologically active, and are in a constant state of damage and repair. This makes the pulmonary system particularly vulnerable to diseases of aging. Aging can be understood as random molecular damage that is unrepaired and accumulates over time, resulting in cellular defects and tissue dysfunction. The breakdown of cellular mechanisms, including stem cell exhaustion, genomic instability, telomere attrition, epigenetic alteration, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, altered intercellular communication, and changes in the extracellular matrix is thought to advance the aging process itself. Chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), and cancers illustrate a pathologic breakdown in these mechanisms beyond normal aging. The immune system becomes less effective with advancing age. There is a low‐level state of chronic inflammation termed inflammaging which is thought to be driven by immunosenescence, the changes in the innate and adaptive immune systems with advancing age that lead to dysregulation and decreased effectiveness of the immune system. These processes of aging lead to expected changes in the form and function of the respiratory system, most notably a loss of lung elasticity, decrease in respiratory muscle strength, increase in ventilation‐perfusion mismatching, and stiffening of the vasculature. The astute clinician is aware of these expected findings and does not often attribute dyspnea to aging alone. Maintaining a low threshold to investigate for comorbid disease and understanding how pulmonary disease presents differently in the elderly than in younger adults can improve clinical outcomes. © 2022 American Physiological Society. Compr Physiol 12:3509‐3522, 2022.

Figure 1. Figure 1. Aging is a lifelong accumulation of molecular damage resulting in cellular defects. Random molecular damage occurs in response to environmental and intrinsic stress. Repair mechanisms protect from damage and can repair damage before it becomes a cellular defect. Normally functioning cellular mechanisms repair molecular and cellular damage. With aging, cellular mechanisms of repair break down and lead to accumulation of cellular defects, resulting in tissue and organ dysfunction. Ultimately, frailty, disability, and disease ensue. Red color represents accumulation of damage. Green color signifies repair or removal of defects. Adapted, with permission, from Kirkwood TBL, 2005 68.
Figure 2. Figure 2. The hallmarks of aging in the lung. This figure represents the hallmark cellular mechanisms of aging 91 with the addition of the lung‐specific extracellular matrix evolution 70. Each individual mechanism has numerous interactions with other mechanisms. Adapted, with permission, from Meiners S, et al., 2015 91.
Figure 3. Figure 3. With aging, the lungs lose elastic recoil or have increased compliance. This means that for any given lung volume there is a lower distending pressure. Lung volumes expressed as percent (%) of total lung capacity and centimeters (cm) of water (H2O) at different age range. Adapted from Turner JM, et al., 1968 148.
Figure 4. Figure 4. Lung parenchyma from (A) nonsmoking 29‐year‐old and (B) a nonsmoking 100‐year‐old who died from pneumonia. The elderly individual has marked, uniform airspace enlargement. Reproduced, with permission of The European Respiratory Society, from Janssens JP, et al., 1999 62.
Figure 5. Figure 5. Closing capacity is the sum of residual volume and closing volume. Closing volume can be thought of as early airway closure and is small or undetectable in young adults. In young adulthood closing capacity is well‐below functional residual capacity. However as closing volume increases, and the closing capacity approaches functional residual capacity (red star), airway closure can result during normal quiet breathing and affect gas exchange. Adapted from Janssens JP, et al., 1999 62.


Figure 1. Aging is a lifelong accumulation of molecular damage resulting in cellular defects. Random molecular damage occurs in response to environmental and intrinsic stress. Repair mechanisms protect from damage and can repair damage before it becomes a cellular defect. Normally functioning cellular mechanisms repair molecular and cellular damage. With aging, cellular mechanisms of repair break down and lead to accumulation of cellular defects, resulting in tissue and organ dysfunction. Ultimately, frailty, disability, and disease ensue. Red color represents accumulation of damage. Green color signifies repair or removal of defects. Adapted, with permission, from Kirkwood TBL, 2005 68.


Figure 2. The hallmarks of aging in the lung. This figure represents the hallmark cellular mechanisms of aging 91 with the addition of the lung‐specific extracellular matrix evolution 70. Each individual mechanism has numerous interactions with other mechanisms. Adapted, with permission, from Meiners S, et al., 2015 91.


Figure 3. With aging, the lungs lose elastic recoil or have increased compliance. This means that for any given lung volume there is a lower distending pressure. Lung volumes expressed as percent (%) of total lung capacity and centimeters (cm) of water (H2O) at different age range. Adapted from Turner JM, et al., 1968 148.


Figure 4. Lung parenchyma from (A) nonsmoking 29‐year‐old and (B) a nonsmoking 100‐year‐old who died from pneumonia. The elderly individual has marked, uniform airspace enlargement. Reproduced, with permission of The European Respiratory Society, from Janssens JP, et al., 1999 62.


Figure 5. Closing capacity is the sum of residual volume and closing volume. Closing volume can be thought of as early airway closure and is small or undetectable in young adults. In young adulthood closing capacity is well‐below functional residual capacity. However as closing volume increases, and the closing capacity approaches functional residual capacity (red star), airway closure can result during normal quiet breathing and affect gas exchange. Adapted from Janssens JP, et al., 1999 62.
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Article Title: Aging and Susceptibility to Pulmonary Disease
 

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Julia Budde, Gwen Skloot. Aging and Susceptibility to Pulmonary Disease. Compr Physiol 2022, 12: 3509-3522. doi: 10.1002/cphy.c210026