Aging and Lung Disease

In the paper

“Despite an age-associated reduction in elastic recoil, due to decreased respiratory strength and chest wall compliance, total lung capacity does not significantly change with age (7, 12, 14, 19).”

What the sources say

• Not checked yetcites [7] source
• Not checked yetcites [12] source
• Not checked yetcites [14] source
• Partly supported

  The Lung function section says total lung capacity, corrected for age, remains unchanged throughout life. The Respiratory system mechanics and Summary sections report reduced chest wall compliance and respiratory muscle strength with age, while Anatomical changes reports degeneration of elastic fibers. The paper does not say that reduced muscle strength and chest wall compliance cause a reduction in elastic recoil; no page numbers are available in our copy. (LLM, conf=0.85)

  cites [19] sourceExperimental — accuracy not yet measured

In the paper

“An age-associated reduction or delay in cytokine, chemokine, or interferon production in response to stimulation can negatively impact innate immune responses in the lung (110).”

What the sources say

• Partly supported

  The Results section reports delayed responses and lower cytokine, chemokine, and interferon production in stimulated PBMCs from older donors. The Discussion suggests these changes could impair immune responses, but the study examined blood cells, not innate immune responses in the lung. No page numbers are available in our copy. (LLM, conf=0.86)

  cites [110] sourceExperimental — accuracy not yet measured

In the paper

“Further, age-associated changes in genomic instability, telomere shortening, epigenetic alterations, cellular senescence, impaired autophagy, and mitochondrial dysfunction may promote IPF development and progression (3, 12, 62, 84, 88, 89, 116, 145).”

What the sources say

• Partly supported

  The “Senescence in age-related disease” section says senescent cells drive pulmonary fibrosis, and its reference identifies idiopathic pulmonary fibrosis. The paper also discusses telomere shortening, DNA damage and epigenetic changes as causes of senescence, but the passages do not establish that each of the listed changes—including impaired autophagy and mitochondrial dysfunction—promotes IPF development or progression. (LLM, conf=0.89)

  cites [3] sourceExperimental — accuracy not yet measured
• Not checked yetcites [12] source
• Partly supported

  The Introduction (page unavailable) describes cellular senescence as age-associated and links it to shortened telomeres and DNA damage. But the paper examines susceptibility to pneumococcal pneumonia and discusses COPD, not IPF development or progression; it does not establish the claimed role for the full list of age-associated changes in IPF. (LLM, conf=0.84)

  cites [62] sourceExperimental — accuracy not yet measured

In the paper

“Age-associated immunosenescence and cellular senescence in response to exposure to cigarette smoke can greatly impact COPD pathogenesis (3, 19, 86).”

What the sources say

• Partly supported

  In “Impact of senescence on human health” (page unavailable), the paper says that defects in the aging immune system may allow senescent cells to persist and identifies cigarette smoke as a disease-causing stressor affecting lung epithelium. It does not specifically establish that these processes greatly affect COPD pathogenesis; its disease discussion uses other conditions as examples. (LLM, conf=0.85)

  cites [3] sourceExperimental — accuracy not yet measured
• Partly supported

  The Immunologic changes section describes age-related immune dysregulation and inflammation that may increase vulnerability to environmental exposures and lung injury; the Summary links this to possible accelerated lung-function decline. Our copy does not establish cigarette-smoke-induced cellular senescence or its impact on COPD pathogenesis. (LLM, conf=0.83)

  cites [19] sourceExperimental — accuracy not yet measured
• Not checked yetcites [86] source

In the paper

“Structural changes, such as subepithelial collagen deposition, goblet cell and mucous gland hyperplasia, as well as ASM hypertrophy and hyperplasia, illustrate that remodeling of airways occurs in asthma patients (98, 99).”

What the sources say

• Partly supported

  The airway-remodeling passage (section labeled Abstract; page unavailable) describes asthma-associated subepithelial fibrosis and extracellular-matrix deposition, along with ASM hypertrophy and hyperplasia. It describes mucus gland hypertrophy, not hyperplasia, and does not identify goblet cell hyperplasia or specifically subepithelial collagen deposition. (LLM, conf=0.87)

  cites [98] sourceExperimental — accuracy not yet measured
• Partly supported

  The Introduction (page not supplied) says that airway smooth muscle may undergo hypertrophy and/or hyperplasia in asthma, and the Conclusions discuss airway remodeling. Our copy does not describe subepithelial collagen deposition or goblet-cell and mucous-gland hyperplasia as features of that remodeling, so it supports only part of the cited sentence. (LLM, conf=0.88)

  cites [99] sourceExperimental — accuracy not yet measured

In the paper

“There is considerable change in lung structure and function with advancing age (summarized in Supplemental Table 1).”

What the sources say

• Not checked yetcites [6] source

In the paper

“Alterations in alveolar depth and acinar airway lumen that occur during compensatory remodeling are associated with advanced age (6).”

What the sources say

• Not checked yetcites [6] source

In the paper

“It is well appreciated that, even in healthy persons, lung function declines starting at the age of 35.”

What the sources say

• Not checked yetcites [7] source
• Not checked yetcites [12] source
• Not checked yetcites [13] source
• Not checked yetcites [14] source
• Not checked yetcites [20] Crapo RO, 1982, Bull. Eur. Physiopathol. Respir.
• Not checked yetcites [21] source

In the paper

“Age-associated changes in intrinsic mechanisms that aid in cell regeneration and repair, such as depletion of adult stem cell reservoirs, mitochondrial dysfunction, increased oxidative stress, and telomere shortening, contribute to an inability of lung cells to maintain baseline homeostasis.”

What the sources say

• Not checked yetcites [3] source

In the paper

“DNA damage in response to compounds, such as those present in cigarette smoke, as well as telomere shortening due to increased demand for injured airway epithelium repair, can result in disease-related senescence and subsequent generation of a secondary subset of senescent cells (5).”

What the sources say

• Not checked yetcites [5] source

In the paper

“A decline in elastic recoil combined with a reduction in the number of elastic attachments of supporting alveoli and increased collagen results in smaller airways closing at higher lung volumes (9, 10).”

What the sources say

• Not checked yetcites [9] source
• Not checked yetcites [10] source

In the paper

“Although the number of alveoli, alveolar ducts, and capillary segments remain constant at adulthood”

What the sources say

• Not checked yetcites [6] source

In the paper

“It is important to note that marked changes in chest wall function and respiratory muscle strength can also impact lung aging and the ability to clear mucus or foreign particulates from the lungs.”

In the paper

“Exposure to extrinsic time-related effects, such as chronic exposure to atmospheric pollution, dusts, particulates, and gases, induce low-level insults to cellular function and accelerate aging of the lung (3).”

What the sources say

• Not checked yetcites [3] source

In the paper

“A reduction in elastic recoil of the lungs and changes in chest wall deformation give rise to increased functional residual capacity with age (7, 14, 17).”

What the sources say

• Not checked yetcites [7] source
• Not checked yetcites [14] source
• Not checked yetcites [17] source

In the paper

“Noninvasive studies in healthy subjects have illustrated age-dependent differences in acinar microstructure (6).”

What the sources say

• Not checked yetcites [6] source

In the paper

“there is a marked increase in alveolar size and alveolar-capillary surface area with aging (6).”

What the sources say

• Not checked yetcites [6] source

In the paper

“Specifically, there is a decline in forced expiratory volume (FEV1) by approximately 30 mL/year and forced vital capacity (FVC) by approximately 20 mL/year, which results in an age-associated decline in the FEV1/FVC ratio (7, 12–14, 20, 21).”

What the sources say

• Not checked yetcites [7] source
• Not checked yetcites [12] source
• Not checked yetcites [13] source
• Not checked yetcites [14] source
• Not checked yetcites [20] Crapo RO, 1982, Bull. Eur. Physiopathol. Respir.
• Not checked yetcites [21] source

In the paper

“Specifically, there is a decline in forced expiratory volume (FEV1) by approximately 30 mL/year and forced vital capacity (FVC) by approximately 20 mL/year, which results in an age-associated decline in the FEV1/FVC ratio (7, 12–14, 20, 21).”

What the sources say

• Not checked yetcites [7] source
• Not checked yetcites [12] source
• Not checked yetcites [13] source
• Not checked yetcites [14] source
• Not checked yetcites [20] Crapo RO, 1982, Bull. Eur. Physiopathol. Respir.
• Not checked yetcites [21] source

In the paper

“Reduced alveolar-capillary density as well as changes to pulmonary vasculature result in a gradual decrease in pulmonary capillary blood volume with aging (24–28).”

What the sources say

• Not checked yetcites [24] source
• Not checked yetcites [25] Peterson DD, 1981, Am. Rev. Respir. Dis.
• Not checked yetcites [26] source
• Not checked yetcites [27] source
• Not checked yetcites [28] source

In the paper

“In healthy aging, a decrease in mucociliary clearance can be conducive to microbial invasion in the lower airways and alveoli (63–65).”

What the sources say

• Not checked yetcites [63] source
• Not checked yetcites [64] source
• Not checked yetcites [65] source

In the paper

“Specifically, there is a decline in forced expiratory volume (FEV1) by approximately 30 mL/year and forced vital capacity (FVC) by approximately 20 mL/year, which results in an age-associated decline in the FEV1/FVC ratio (7, 12–14, 20, 21).”

What the sources say

• Not checked yetcites [7] source
• Not checked yetcites [12] source
• Not checked yetcites [13] source
• Not checked yetcites [14] source
• Not checked yetcites [20] Crapo RO, 1982, Bull. Eur. Physiopathol. Respir.
• Not checked yetcites [21] source

In the paper

“Normal lung aging is associated with multiple structural and functional changes in the respiratory tract (6, 10).”

• Also stated in: § CONCLUSIONS AND FUTURE DIRECTIONS · plain

  “Normal lung aging is associated with multiple structural and functional changes in the respiratory tract, with many of these changes contributing to decreased lung function, altered pulmonary remodeling, diminished regeneration, and enhanced susceptibility to pulmonary disease.”

What the sources say

• Not checked yetcites [6] source
• Not checked yetcites [10] source

In the paper

“Due to the heterogeneity of the aging population and highly variable rates of lung aging, the interpretation of healthy or normal lung function in older persons and disease diagnosis can be problematic.”

In the paper

“Experimental studies have illustrated that there is an age-associated increase in bronchoepithelial cell apoptosis, resulting in decreased cell numbers present in aged lung (61).”

What the sources say

• Not checked yetcites [61] source

In the paper

“suggesting that mechanical forces are strengthened in the peripheral airways (100).”

What the sources say

• Not checked yetcites [100] source

In the paper

“which may indicate that contractions of larger intrapulmonary airways decline with aging (100).”

What the sources say

• Not checked yetcites [100] source

In the paper

“In the aged lung, endothelial cell senescence and a decline in the concentration in vascular endothelial growth factors can directly impacts angiogenesis by limiting vascular growth.”

In the paper

“Experimental aging models have illustrated decreased expression of γ-smooth muscle actin and desmin in aged lung”

What the sources say

• Not checked yetcites [100] source

In the paper

“Taken together, diminished and/or dysregulated endothelial repair and regeneration in aged lung promotes increased susceptibility of older persons to disease processes such as pulmonary sepsis and pulmonary hypertension.”

In the paper

“Persistent low-grade inflammation in the lower respiratory tract can augment proteolytic and oxidant-mediated injury to the lung matrix, resulting in alveolar loss and subsequent impairment of gas exchange across the alveolar membrane.”

In the paper

“In experimental models, DC migration into the aged lung during influenza infection is reduced (115).”

What the sources say

• Not checked yetcites [115] source

In the paper

“Senescence in AEC2s can lead to a critical decline in alveolar epithelial stem cell renewal.”

In the paper

“Taken together, the diminished/dysregulated responses of AM to pathogenic stimuli and impaired ability to promote resolution contribute to excessive inflammation and tissue damage in the aged lung.”

In the paper

“Interestingly, α-smooth muscle actin and vimentin expression in the distal airway may be increased in aged lung”

What the sources say

• Not checked yetcites [100] source

In the paper

“Defects in DC function, in combination with intrinsic changes in T cells, contribute to blunted adaptive immune responses in the elderly lung.”

In the paper

“Altered PRR expression and/or changes in downstream signaling cascades may underlie dysregulated DC responses in older persons (114, 116).”

What the sources say

• Not checked yetcites [114] source
• Not checked yetcites [116] source

In the paper

“Age-associated changes in the molecular composition of epithelial lining fluid, specifically a decrease in antioxidants, can also impact lung function (66).”

What the sources say

• Not checked yetcites [66] source

In the paper

“Research using acellularized lungs, where all cells have been removed and only the ECM remains, has illustrated that ECM from aged lung contains less structural protein diversity (93).”

What the sources say

• Not checked yetcites [93] source

In the paper

“There is an age-related decrease in the ratio of proliferating to apoptotic AECs (83).”

What the sources say

• Not checked yetcites [83] Walski M, 2009, J. Physiol. Pharmacol.

In the paper

“Experimental studies have illustrated an age-associated increase in ROS levels that corresponds with decreased antioxidative responses in AM (111, 112).”

What the sources say

• Not checked yetcites [111] source
• Not checked yetcites [112] source

In the paper

“Despite comparable cell numbers, differentiation, and morphology in the young and aged, DCs from older persons exhibit impaired phagocytosis of antigen (113, 114).”

What the sources say

• Not checked yetcites [113] source
• Not checked yetcites [114] source

In the paper

“In addition, age-related alterations in pathogen recognition, decreased PRR expression, and diminished responses to secondary signaling may underlie increased susceptibility of older persons to infectious stimuli (109).”

What the sources say

• Not checked yetcites [109] source

In the paper

“Age-associated changes in the composition and function of AEC1s, AEC2s, fibroblasts and endothelial and ASM cells can be factors in the increased susceptibility of older persons to the development and progression of lung disorders.”

In the paper

“An age-associated impairment in AEC2 function, due to increased cellular senescence, contributes to the highly proinflammatory and oxidative environment within the lung (66).”

What the sources say

• Not checked yetcites [66] source

In the paper

“Normal lung aging is characterized by increased collagen, which promotes age-related changes in elasticity and airspace enlargement (6).”

What the sources say

• Not checked yetcites [6] source

In the paper

“Due to changes in lung function and anatomy as well as lung antioxidant defenses, the aged lung is more susceptible to environmental exposure–induced injury (19, 86).”

What the sources say

• Not checked yetcites [19] source
• Not checked yetcites [86] source

In the paper

“In summary, age-associated changes in T cell–adaptive immune responses can lead to increased susceptibility to infectious stimuli and prolonged and more severe disease severity.”

In the paper

“Experimental models of infection or injury have demonstrated that neutrophil chemotaxis is dysregulated (123).”

What the sources say

• Not checked yetcites [123] Nomellini V, 2012, Aging Dis

In the paper

“Age-associated changes in regulation and function of innate cell types, such as AMs, DCs, and NK cells, can promote increased susceptibility of older persons to the development and progression of lung disorders.”

In the paper

“Experimental studies have illustrated that altered function and phenotype of NK cells with advanced aged underlies increased susceptibility of older persons to infectious stimuli (127).”

What the sources say

• Not checked yetcites [127] source

In the paper

“Low levels of inflammation present in normal aged lung as well as changes in the nonhematopoietic environment may underlie reduced recruitment and maturation of NK cells (129).”

What the sources say

• Not checked yetcites [129] source

In the paper

“An age-associated reduction in BAL antioxidant levels and composition may underlie increased susceptibility of older persons to exposure with environmental toxins, such as ozone, cigarette smoke, and particulate matter (66).”

What the sources say

• Not checked yetcites [66] source

In the paper

“Specifically, augmented and prolonged innate inflammation and diminished adaptive regulation can increase the likelihood of lung disorders in the elderly.”

In the paper

“Multiple studies have illustrated an age-associated decline in B cell development, specifically a decreased transition from the presence of naïve to mature B cells (135).”

What the sources say

• Not checked yetcites [135] source

In the paper

“Specifically, experimental murine studies have demonstrated a decline in the number pro-B, pre-B, and immature B cell subsets present in older animals (135).”

What the sources say

• Not checked yetcites [135] source

In the paper

“Poor prognosis and recovery in pulmonary diseases have been attributed to age-related changes in innate and adaptive immune responses in the lung.”

In the paper

“Changes in cytokine signaling pathways may also increase the susceptibility of neutrophils undergoing apoptosis (124).”

What the sources say

• Not checked yetcites [124] source

In the paper

“Multiple age-associated changes in T cell numbers and function may underlie increased susceptibility of older persons to environmental stimuli.”

In the paper

“Age-associated changes in the structure, function, and control of the respiratory system can greatly influence COPD susceptibility in older persons (6–10).”

What the sources say

• Not checked yetcites [6] source
• Not checked yetcites [7] source
• Not checked yetcites [8] source
• Not checked yetcites [9] source
• Not checked yetcites [10] source

In the paper

“An age-associated increase in NK cell senescence has been shown to impair antiviral immune responses in response to influenza (3, 128).”

What the sources say

• Not checked yetcites [3] source
• Not checked yetcites [128] source

In the paper

“Increased and prolonged neutrophil recruitment in the aged lung can have devastating effects on lung parenchyma (125).”

What the sources say

• Not checked yetcites [125] source

In the paper

“Changes in immature B cell migration and an increase in age-associated B cells can decrease repertoire diversity (135).”

What the sources say

• Not checked yetcites [135] source

In the paper

“Increased telomere shortening in aging diminishes AEC1 regeneration by AEC2s (83, 84).”

What the sources say

• Not checked yetcites [83] Walski M, 2009, J. Physiol. Pharmacol.
• Not checked yetcites [84] source

In the paper

“Age-associated impairments in innate and adaptive immune responses in the lung may contribute to increased susceptibility of older persons developing an asthma exacerbation (3, 19, 107, 109, 110).”

What the sources say

• Not checked yetcites [3] source
• Not checked yetcites [19] source
• Not checked yetcites [107] source

In the paper

“While it is appreciated that there is a decline in lung function in healthy older persons, increased airway remodeling and inflammation that occur with asthma can contribute to an accelerated decline in lung function.”

In the paper

“An age-dependent increase in cytotoxic CD8+ and memory CD4+ T cells in the airways of COPD patients may further disease progression (86, 130, 132).”

What the sources say

• Not checked yetcites [86] source
• Not checked yetcites [130] source
• Not checked yetcites [132] source

In the paper

“Aging is associated with increased susceptibility to interstitial lung diseases, primarily IPF.”

In the paper

“Impaired phagocytosis and clearance of cellular debris by airway macrophages in COPD result in persistent inflammation (85, 104).”

What the sources say

• Not checked yetcites [85] source
• Not checked yetcites [104] source

In the paper

“Immunosenescence contributes to the production of oxygen free radicals and augments production of proinflammatory cytokines.”

In the paper

“Age-associated changes in composition and function of AEC1s, AEC2s, fibroblasts, and endothelial and ASM cells underlie increased susceptibility of older persons to the development and progression of lung disorders.”

In the paper

“Age-associated changes in intrinsic mechanisms that aid in cell regeneration and repair, such as depletion of adult stem cell reservoirs, mitochondrial dysfunction, increased oxidative stress, and telomere shortening, contribute to an inability of lung cells to maintain baseline homeostasis.”

In the paper

“Immunosenescence contributes to the production of oxygen free radicals and augments production of proinflammatory cytokines.”

In the paper

“Many age-associated risk factors contribute to the increased susceptibility of older persons to bacterial CAP (Supplemental Table 2).”

What the sources say

• Not checked yetcites Supplemental Table 2

In the paper

“Due to reduced immunity, coexisting comorbidities, and age-associated functional limitations, the incidence of severe sepsis and septic shock increases in older individuals (104, 146).”

What the sources say

• Not checked yetcites [104] source
• Not checked yetcites [146] source

In the paper

“Also, depressed clearance mechanisms, such as cough, oral and mucociliary clearance, and swallowing disorders can also increase susceptibility (40, 63, 64, 140).”

What the sources say

• Not checked yetcites [40] source
• Not checked yetcites [63] source
• Not checked yetcites [64] source
• Not checked yetcites [140] Incalzi RA, 1989, Compr. Gerontol. A

In the paper

“Sustained inflammation of the lower respiratory tract may predispose older adults to increased vulnerability to toxic environmental exposure and accelerated lung function decline.”

In the paper

“Bacteria, especially Streptococcus pneumoniae, are the most common pathogens that commonly cause CAP in the elderly (62).”

What the sources say

• Not checked yetcites [62] source

In the paper

“Genetic background and lifestyle promote age-related changes in the lung and contribute to the development and progression of airway diseases and increased susceptibility to infectious stimuli and toxins.”

In the paper

“Lung aging is highly complex and results from accumulated changes between injury and repair to lung cellular systems.”

In the paper

“Age-associated alterations in immune surveillance, specifically decreased innate and adaptive immune responses, and dysfunctional immune response regulation can be responsible for increased lung pathology in response to infectious stimuli (3, 62, 106, 110, 114, 135).”

What the sources say

• Not checked yetcites [3] source
• Not checked yetcites [62] source
• Not checked yetcites [106] source

In the paper

“Genetic background and lifestyle promote age-related changes in the lung and contribute to the development and progression of airway diseases and increased susceptibility to infectious stimuli and toxins.”

In the paper

“Sustained inflammation of the lower respiratory tract may predispose older adults to increased vulnerability to toxic environmental exposure and accelerated lung function decline.”

In the paper

“Genetic background and lifestyle promote age-related changes in the lung and contribute to the development and progression of airway diseases and increased susceptibility to infectious stimuli and toxins.”