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Cited by 466Interstitial Lung Diseases and Idiopathic Pulmonary FibrosisChronic Obstructive Pulmonary Disease (COPD) ResearchTransplantation: Methods and Outcomes

Aging and Lung Disease

Open access
Cho, Soo Jung, Stout-Delgado, Heather W.·2020·Annual Review of Physiology
DOI 10.1146/annurev-physiol-021119-034610PMC PMC7998901
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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.

AI snapshot

Written from the paper’s full text.

TL;DR

This review synthesizes how normal lung aging and immunosenescence alter pulmonary structure, cellular repair, and immune responses, increasing susceptibility to COPD, IPF, ARDS, pneumonia, and asthma exacerbations. It emphasizes that senescence, oxidative stress, ECM remodeling, and innate/adaptive immune dysfunction converge to impair lung homeostasis and disease outcomes.

Key findings

  • Natural lung aging causes structural and physiologic changes: increased alveolar size and alveolar-capillary surface area, reduced elastic recoil, increased functional residual capacity, and declines in FEV1 of approximately 30 mL/year and FVC of approximately 20 mL/year, lowering the FEV1/FVC ratio; total lung capacity does not significantly change with age.
  • Cellular aging includes increased bronchoepithelial apoptosis, AEC2 senescence, mitochondrial dysfunction, impaired autophagy, decreased proliferating-to-apoptotic AEC ratio, ECM stiffening with increased collagen and decreased elastin/laminin/fibronectin, endothelial dysfunction, and altered airway smooth muscle markers.
  • Immunosenescence includes age-associated declines in alveolar macrophage phagocytosis, impaired dendritic cell antigen phagocytosis and migration, decreased neutrophil CD16 with increased superoxide and impaired phagocytosis, altered NET-mediated killing, reduced NK cell function, decreased naïve T cells with increased memory T cells, and impaired B cell development/repertoire diversity.
  • Disease links include COPD sharing aging features but with more disorganized collagen and increased collagen, fibronectin, and laminin; IPF survival of less than five years post diagnosis; severe sepsis mortality of 50–60% in elderly patients; and increased pneumonia susceptibility from impaired clearance and bacterial adhesion.

Methods

  • Design: narrative review; no primary experiments or systematic review methodology are described.
  • Data or sample: synthesis of published human, murine, and in vitro literature; no original human or animal cohort is analyzed.
  • Main analysis: thematic overview of physiologic, structural, cellular, immune, and disease-related changes in the aging lung, with 149 cited references.

Limitations

  • The paper states that more detailed mechanistic studies are needed to validate genetic determinants of disease progression, understand interactions between immune and lung cell types, clarify when lung aging begins, and link biologic hallmarks of aging to lung phenotypes and disease progression.
  • Evident from the text: as a narrative review, it does not report a systematic search strategy, inclusion criteria, quality appraisal, or primary data, and it synthesizes heterogeneous human, murine, and in vitro findings.
  • The paper notes that interpretation of healthy or normal lung function in older persons and disease diagnosis can be problematic because of heterogeneity and variable rates of lung aging; height, gender, weight, and ethnicity partly explain FEV1/FVC differences, and reference standards remain to be fully elucidated.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1146/annurev-physiol-021119-034610

Cites

153 of 153 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

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  • Premisecitation

    There is considerable change in lung structure and function with advancing age.

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

    Alterations in alveolar depth and acinar airway lumen that occur during compensatory remodeling are associated with advanced age.

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

    Even in healthy persons, lung function declines starting at the age of 35.

    “It is well appreciated that, even in healthy persons, lung function declines starting at the age of 35.”
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    • cites [20] Crapo RO, 1982, Bull. Eur. Physiopathol. Respir.

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  • Premisecitation

    Age-associated changes in intrinsic mechanisms that aid 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.

    “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.”
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    DNA damage from compounds such as cigarette smoke and telomere shortening due to increased demand for injured airway epithelium repair can result in disease-related senescence and generation of a secondary subset of senescent cells.

    “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).”
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    Premisecitation

    Pulmonary function impairment is a predictor for morbidity and mortality and may promote the development of multiple disease processes.

    “Longitudinal studies have illustrated that pulmonary function impairment is a predictor for morbidity and mortality and may promote the development of multiple disease processes (1, 2).”
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    Senescent cells display a genetic and morphologic phenotype distinct from growth-competent cells and can have a detrimental impact on neighboring cells, structural components, and composition of the extracellular matrix.

    “Senescent cells display a genetic and morphologic phenotype that is distinct from growth-competent cells and can have a detrimental impact on neighboring cells, structural components, and composition of the extracellular matrix (ECM) (3).”
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    Premisecitation

    Elastic recoil of the lungs is reduced with aging and gives rise to an increase in end-expiratory lung volume.

    “Elastic recoil of the lungs, due to a reduction in the surface tension forces caused by increased individual diameters of alveoli, is reduced with aging and gives rise to an increase in end-expiratory lung volume (7, 8).”
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    Interpretationcitation

    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.

    “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.”
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    Premisecitation

    In healthy aging, common cellular stresses can yield primary senescent cells that diminish tissue-repair capacity due to cell cycle arrest in progenitor cells and increase production of proinflammatory and matrix-degrading molecules.

    “In healthy aging, common cellular stresses can yield primary senescent cells that diminish tissue-repair capacity due to cell cycle arrest in progenitor cells and increase production of proinflammatory and matrix-degrading molecules (3, 4).”
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    Interpretationreasoning

    Some airways may be narrowed or closed during normal tidal breathing in older individuals, thereby increasing functional residual capacity and reducing expiratory airflow from the lungs.

    “As a result, some airways may be narrowed or closed during normal tidal breathing in older individuals, thereby increasing the functional residual capacity and reducing the expiratory airflow from the lungs (12, 13).”
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    Interpretationnone given

    Senescence in circulating immune cells can impact lung aging and disease progression.

    “While cellular senescence in resident cells in response to intrinsic and extrinsic factors may lead to both age- and disease-related changes in the lung, it is important to note that senescence in circulating immune cells can also impact lung aging and disease progression.”
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    Premisecitation

    As a person ages, there is a decrease in resting arterial oxygen tension, which gives rise to diminished gas exchange in the lungs.

    “As a person ages, there is a decrease in resting arterial oxygen tension, which gives rise to diminished gas exchange in the lungs (7, 12, 22).”
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    Premisecitation

    Many of these changes give rise to decreased lung function, altered pulmonary remodeling, diminished regeneration, and enhanced susceptibility to pulmonary disease.

    “Many of these changes, as highlighted in Figure 1, give rise to decreased lung function, altered pulmonary remodeling, diminished regeneration, and enhanced susceptibility to pulmonary disease (7, 10).”
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    Premisecitation

    Aged DCs maintain the ability to upregulate chemokines and chemokine receptors but exhibit decreased migratory capacity in response to stimuli.

    “In addition, aged DCs maintain the ability to upregulate chemokines and chemokine receptors but exhibit decreased migratory capacity in response to stimuli (114).”
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    Interpretationnone given

    Changes in fibroblast function and ECM composition can increase susceptibility of the aged lung to injury and disease progression.

    “Changes in fibroblast function and ECM composition can increase susceptibility of the aged lung to injury and disease progression.”
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    Premisenone given

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

    “Poor prognosis and recovery in pulmonary inflammatory diseases have been attributed to age-related changes in innate and adaptive immune responses in the lung.”
    • Also stated in: § CONCLUSIONS AND FUTURE DIRECTIONS · plain
      “Poor prognosis and recovery in pulmonary inflammatory diseases have been attributed to age-related changes in innate and adaptive immune responses in the lung.”
    • Also stated in: § CONCLUSIONS AND FUTURE DIRECTIONS · plain
      “and recovery in pulmonary inflammatory diseases have been attributed to age-related changes in innate and adaptive immune responses in the lung.”
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  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisenone given

    Immunosenescence results from an imbalance between inflammatory and anti-inflammatory mechanisms.

    “Immunosenescence, or aging of the immune system, results from an imbalance between inflammatory and anti-inflammatory mechanisms.”
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    Premisecitation

    An age-associated alteration in pathogen-mediated destruction by NETs further contributes to impaired bacterial clearance and may underlie increased susceptibility of older persons to infection.

    “An age-associated alteration in pathogen-mediated destruction by NETs further contributes to impaired bacterial clearance and may underlie increase susceptibility of older persons to infection (122).”
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    Premisenone given

    Chronic antigen stimulation throughout a lifetime as well as oxidative stress and production of oxygen free radicals augment production of proinflammatory cytokines.

    “Chronic antigen stimulation throughout a lifetime as well as oxidative stress and the production of oxygen free radicals augment production of proinflammatory cytokines.”
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    Interpretationnone given

    Age-associated changes in immune cell function can promote increased susceptibility of older persons to development and progression of lung disorders.

    “Age-associated changes in immune cell function can promote increased susceptibility of older persons to the development and progression of lung disorders.”
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    Premisecitation

    Although the number of circulating neutrophils is preserved in older persons, a decrease in CD16 expression results in augmented superoxide generation and impaired neutrophil-mediated phagocytosis.

    “Although the number of circulating neutrophils is preserved in older persons, a decrease in CD16 expression results in augmented superoxide generation and impaired neutrophil-mediated phagocytosis (120, 121).”
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    Premisecitation

    There is an age-associated decline in phagocytic capacity in alveolar and pulmonary macrophages, which results in impaired and/or delayed pathogen clearance from the lung.

    “There is an age-associated decline in phagocytic capacity in alveolar and pulmonary macrophages, which results in impaired and/or delayed pathogen clearance from the lung (106–108).”
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    Premisecitation

    There is an age-associated reduction in the upregulation of costimulatory molecules critical for T cell priming and dysregulated cytokine production by DCs.

    “There is an age-associated reduction in the upregulation of costimulatory molecules critical for T cell priming and dysregulated cytokine production by DCs (115, 117).”
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    Interpretationreasoning

    The conducting airways play a pivotal role in maintaining lung homeostasis and age-associated changes in composition and function can be partly responsible for increased susceptibility of older persons to lung disorders.

    “In sum, the conducting airways play a pivotal role in maintaining lung homeostasis and age-associated changes in composition and function can be partly responsible for increased susceptibility of older persons to lung disorders.”
    Quote in the paperSubstantial claim

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    Premisecitation

    Decreased CD4+ and CD8+ T cell responses in the elderly can impair immunity to influenza vaccination and cytotoxicity against the influenza virus, respectively.

    “Decreased CD4+ and CD8+ T cell responses in the elderly can impair immunity to influenza vaccination and cytotoxicity against the influenza virus, respectively (132, 133).”
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    Premisecitation

    While the functional ability to produce antibody remains intact, age-associated changes in antibody specificity and antigen affinity result in a diminished ability to mount robust antibody responses in older persons.

    “While the functional ability to produce antibody remains intact, age-associated changes in antibody specificity and antigen affinity result in a diminished ability to mount robust antibody responses in older persons (135).”
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    Premisecitation

    Memory T cell responses, T cell receptor repertoire diversity, T helper cell differentiation, and T helper cell activity diminish with age.

    “Further, memory T cell responses, T cell receptor repertoire diversity, T helper cell differentiation, and T helper cell activity diminish with age (131, 132).”
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    Interpretationreasoning

    In summary, chronic antigen stimulation throughout a lifetime as well as oxidative stress and the production of oxygen free radicals impair adaptive immune responses in the lung.

    “In summary, chronic antigen stimulation throughout a lifetime as well as oxidative stress and the production of oxygen free radicals impair adaptive immune responses in the lung.”
    Quote in the paperNot a substantial claim

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    Premisecitation

    There is an age-associated delay in neutrophil recruitment or, in some instances, increased neutrophil accumulation due to a failure to disperse at the site of infection.

    “Specifically, there is an age-associated delay in neutrophil recruitment or, in some instances, increased neutrophil accumulation due to a failure to disperse at the site of infection (123).”
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    • cites [123] Nomellini V, 2012, Aging Dis

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    • Rests on an assumption: Findings from experimental animal models of infection or injury are representative of human aging and can support conclusions about older persons.

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    Premisecitation

    Increasing numbers of recruited neutrophils can promote the development of edema, enhanced disease severity, prolonged inflammation, and pulmonary tissue damage.

    “Increasing numbers of recruited neutrophils can promote the development of edema, enhanced disease severity, prolonged inflammation, and pulmonary tissue damage (125, 126).”
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    Premisecitation

    In healthy older adults, there is an increased proportion of neutrophils and a lower percentage of macrophages present in bronchoalveolar lavage (BAL) fluids.

    “In healthy older adults, there is an increased proportion of neutrophils and a lower percentage of macrophages present in bronchoalveolar lavage (BAL) fluids (121).”
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    Premisecitation

    There is an age-associated reduction in naïve T cell numbers that corresponds with increased memory T cell numbers.

    “There is an age-associated reduction in naïve T cell numbers that corresponds with increased memory T cell numbers (131).”
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    Premisecitation

    The ratio of CD4+ to CD8+ lymphocytes in the BAL fluid has been shown to increase with age, suggesting a decrease in the number of naïve T cells available that can be converted to memory cells against a novel antigen.

    “Specifically, the ratio of CD4+ to CD8+ lymphocytes in the BAL fluid has been shown to increase with age, suggesting a decrease in the number of naïve T cells available that can be converted to memory cells against a novel antigen (131, 132).”
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    Premisecitation

    Glycolytic reprogramming has been shown to play an important role in the pathogenesis of lung fibrosis, with higher glycolytic activity detected in fibrotic areas.

    “Glycolytic reprogramming has been shown to play an important role in the pathogenesis of lung fibrosis, with higher glycolytic activity detected in fibrotic areas (143).”
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    Premisecitation

    COPD is associated with abnormalities in ciliary function and decreased mucociliary clearance, which can lead to increased incidence of recurrent infections, bronchiectasis, and airway obstruction.

    “COPD is also associated with abnormalities in ciliary function and decreased mucociliary clearance, which can lead to increased incidence of recurrent infections, bronchiectasis, and airway obstruction (19, 63, 64, 86, 140).”
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    Interpretationreasoning

    Although allergies and asthma can affect all age groups, asthma in the elderly in regards to inflammation and clinical manifestation is different from asthma in younger patients.

    “Taken together, although allergies and asthma can affect all age groups, asthma in the elderly in regards to inflammation and clinical manifestation is different from asthma in younger patients.”
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    Premisecitation

    While mortality from asthma has declined in the majority of age groups, the number of deaths in elderly has remained constant.

    “While mortality from asthma has declined in the majority of age groups, the number of deaths in elderly has remained constant (140).”
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    • cites [140] Incalzi RA, 1989, Compr. Gerontol. A

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    Interpretationcitation

    Many 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, illustrating that the process of aging is a contributing factor for disease progression.

    “Interestingly, 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 (Figure 2) (7, 10, 16).”
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    Premisecitation

    Increased and prolonged neutrophil recruitment in the COPD lung can have devastating effects on lung parenchyma and can enhance disease severity, prolong inflammation, and cause further tissue damage.

    “Increased and prolonged neutrophil recruitment in the COPD lung can have devastating effects on lung parenchyma and can enhance disease severity, prolong inflammation, and cause further tissue damage (107, 125, 126).”
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    Premisecitation

    Macrophages, which can produce multiple proinflammatory cytokines and secrete MMPs, are the most abundant cell type in the BAL fluid of COPD patients, and increased numbers correlate with disease severity.

    “Specifically, macrophages, which can produce multiple proinflammatory cytokines and secrete MMPs, are the most abundant cell type in the BAL fluid of COPD patients, and increased numbers correlate with disease severity (85, 86, 104).”
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    Premisecitation

    Despite an age-associated decline in IgE production, a relationship still exists between heightened IgE levels and the development of asthma in the elderly.

    “Despite an age-associated decline in IgE production, a relationship still exists between heightened IgE levels and the development of asthma in the elderly (140).”
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    • cites [140] Incalzi RA, 1989, Compr. Gerontol. A

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    Premisecitation

    IPF is a process that is characterized by epithelial cell injury, fibroblast expansion, augmented ECM remodeling, and lung architecture destruction.

    “IPF is a process that is characterized by epithelial cell injury, fibroblast expansion, augmented ECM remodeling, and lung architecture destruction (87, 141).”
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    Premisecitation

    Acute exacerbations of COPD (AECOPD) are common in patients with severe and very severe COPD and are characterized by increased dyspnea, purulence, and augmented sputum volume.

    “Acute exacerbations of COPD (AECOPD) are common in patients with severe and very severe COPD and are characterized by increased dyspnea, purulence, and augmented sputum volume (86, 137).”
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    Premisecitation

    Aged fibroblasts have augmented glucose utilization and increased resistance to apoptosis, which may underlie increased susceptibility of the aged lung to fibrogenesis.

    “Specifically, aged fibroblasts have augmented glucose utilization and increased resistance to apoptosis, which may underlie increased susceptibility of the aged lung to fibrogenesis (144).”
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    Premisecitation

    When compared to aging lungs, there is a significant increase in collagen, fibronectin, and laminin, with more disorganized collagen fibers present in COPD lungs.

    “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 (139).”
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    Premisecitation

    Elderly patients exhibit reduced tolerance to systemic inflammation, with increased mortality when compared with younger septic individuals.

    “Further, elderly patients exhibit reduced tolerance to systemic inflammation, with increased mortality when compared with younger septic individuals (146–148).”
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    Premisecitation

    Patients with severe sepsis and septic shock often require mechanical ventilation, which in the elderly is independently associated with increased mortality.

    “Patients with severe sepsis and septic shock often require mechanical ventilation, which in the elderly is independently associated with increased mortality (146, 147).”
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    Premisecitation

    ARDS, the most severe form of acute lung injury, is a severe respiratory illness, with older patients having a higher risk of ARDS development.

    “ARDS, the most severe form of acute lung injury, is a severe respiratory illness, with older patients having a higher risk of ARDS development (146).”
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  • May combine two claims.

    Interpretationreasoning

    Many of the structural and functional changes of normal lung aging contribute to decreased lung function, altered pulmonary remodeling, diminished regeneration, and enhanced susceptibility to pulmonary disease.

    “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.”
    Quote in the paperSubstantial claim

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    Premisecitation

    Upregulation of epithelial cell surface receptors in response to chronic inflammation increases bacterial adhesion and accumulation in the aged lung and correlates with susceptibility to pneumonia.

    “Upregulation of epithelial cell surface receptors in response to chronic inflammation increases bacterial adhesion and accumulation in the aged lung and correlates with susceptibility to pneumonia (62, 97).”
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    Premisecitation

    Mortality rates associated with severe sepsis also increase with age, with a 50-60% mortality rate in elderly patients.

    “Mortality rates associated with severe sepsis also increase with age, with a 50–60% mortality rate in elderly patients (146).”
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  • The paper relies on this without support.

    Findings from experimental animal models of infection or injury are representative of human aging and can support conclusions about older persons.

    “Experimental models of infection or injury have demonstrated that neutrophil chemotaxis is dysregulated (123).”
    “In experimental models, DC migration into the aged lung during influenza infection is reduced (115).”

  • The paper relies on this without support.

    Findings from experimental murine studies of B cell development are representative of human B cell aging.

    “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).”
2 of 2

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Immune cell disorganization associated with aging may contribute to the heightened severity of COVID-19 and COPD in the elderly.

    “Notably, immune cell disorganization associated with aging may contribute to the heightened severity of COVID-19 and chronic obstructive pulmonary disease (COPD) in the elderly.169,177”

    From Inflammation and aging: signaling pathways and intervention therapies (2023) · cites this paper as [169]

    The Chronic Obstructive Pulmonary Disease section (page unavailable) links age-associated immune changes to COPD pathogenesis and describes immune-cell changes associated with greater disease severity. The full-text search found no passage addressing COVID-19 or SARS-CoV-2, so this source does not support the COVID-19 part of the claim. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • The aging process brings about a decline in mucociliary clearance and heightened vulnerability to pulmonary infections.

    “The aging process brings about notable transformations in the structure and function of the lungs, including a decline in mucociliary clearance and heightened vulnerability to pulmonary infections.168,169”

    From Inflammation and aging: signaling pathways and intervention therapies (2023) · cites this paper as [169]

  • Age-related lung alterations contribute to the onset and progression of lung diseases such as idiopathic pulmonary fibrosis and chronic obstructive pulmonary disease.

    “These alterations contribute to the onset and progression of various lung diseases like idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD).169”

    From Inflammation and aging: signaling pathways and intervention therapies (2023) · cites this paper as [169]

Cites

Flagged first, then by citations

Research works printed but not linked: 8

  1. Crapo RO, 1982, Bull. Eur. Physiopathol. Respir., 18, 419
  2. Peterson DD, 1981, Am. Rev. Respir. Dis., 124, 387
  3. Crapo JD, 1982, Am. Rev. Respir. Dis., 125, 740
  4. Rose MC., 1992, Am. J. Physiol., 263, L413
  5. Greene CM, 2005, Arch. Immunol. Ther. Exp., 53, 418
  6. Walski M, 2009, J. Physiol. Pharmacol., 60, 121
  7. Nomellini V, 2012, Aging Dis, 3, 234
  8. Incalzi RA, 1989, Compr. Gerontol. A, 3, 65

Cited by

Sorted by citations

Related

Authors
Cho, S. J., & Stout-Delgado, H. W.
Affiliations
Weill Cornell Medicine (US)
ORCID
Venue
Annual Review of Physiology
Publisher
Annual Reviews
Published
2020-02-10
Volume
82
Issue
1
Pages
433-459
ISSN
  • 0066-4278 (ISSN-L)
  • 1545-1585
DOI
10.1146/annurev-physiol-021119-034610
PMC
PMC7998901
OpenAlex
W2984453596
Semantic Scholar
5c4fdd1b28fbf29457689f29b4a53546ad992c99
Cited by
458
References
146
Citations by year
2026: 50 · 2025: 113 · 2024: 109 · 2023: 94 · 2022: 53 · 2021: 21 · 2020: 14 · 2019: 2
FWCI
3.79
Type
journal article
Language
en
Open access
Locations
  • Annual Review of Physiology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health
  • National Institute on Aging (R01AG056699, R01AG052530)
  • National Heart, Lung, and Blood Institute (K08HL138285)
Topics
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Chronic Obstructive Pulmonary Disease (COPD) Research
  • Health Sciences › Medicine › Surgery › Transplantation: Methods and Outcomes
Keywords
lung aging, chronic obstructive pulmonary disease, interstitial pulmonary fibrosis, lung remodeling, lung infection susceptibility, immunosenescence, lung function decline
MeSH terms
Aged, Aging, Humans, Lung, Lung Diseases, Middle Aged, Cellular Senescence

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-10.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-10.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

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