Changes in lung permeability and lung mechanics accompany homeostatic instability in senescent mice

2003 ◽  
Vol 95 (4) ◽  
pp. 1681-1687 ◽  
Author(s):  
Clarke G. Tankersley ◽  
Jessica A. Shank ◽  
Susan E. Flanders ◽  
Shawn E. Soutiere ◽  
Richard Rabold ◽  
...  
Keyword(s):  
Lung Disease ◽  
Lung Volume ◽  
Inbred Mouse ◽  
Body Weight Loss ◽  
The Elderly ◽  
Lung Mechanics ◽  
Barrier Dysfunction ◽  
Lung Permeability ◽  
Age Dependent ◽  
Imminent Death

Aging and lung disease are recognized factors that increase mortality risk in subjects exposed to ambient particulate matter (PM). In an effort to understand the mechanisms of enhanced susceptibility, the present study examined an inbred mouse model of senescence to 1) determine changes in lung permeability as animals approach the end-of-life and 2) characterize age-dependent changes in lung mechanics in presenescent and terminally senescent mice. The clearance of technetium-99m (99mTc)-diethylenetriamine pentaacetic acid (DTPA) was used to test the hypothesis that lung permeability increases with age and enhances uptake of soluble components of PM principally during the period several weeks before death in AKR/J mice. Quasistatic pressure-volume curves were conducted on robust and on terminally senescent AKR/J mice several weeks before death to assess the relative importance of lung mechanics. Abrupt body weight loss was used to signal imminent death because it accompanies indexes of physiological aging and terminal senescence. 99mTc-DTPA clearance from the lung 30 min after tracheal instillation was significantly ( P < 0.05) enhanced in senescent mice. Age-dependent changes in lung mechanics were indicative of significant ( P < 0.05) decrements in lung volume and compliance several weeks before death. Thus, during a period of homeostatic instability leading toward natural death, AKR/J mice showed enhanced permeability of soluble particles despite a decrease in lung volume and concomitant alveolar surface area. These results suggest that pulmonary epithelial-endothelial barrier dysfunction occurs in terminally senescent mice just before death. Furthermore, this senescent-dependent increase in lung permeability may be a contributing factor for increased PM susceptibility in the elderly and patients with lung disease.

scholarly journals Neonatal hyperoxia enhances age-dependent expression of SARS-CoV-2 receptors in mice

2020 ◽  
Author(s):  
Min Yee ◽  
E. David Cohen ◽  
Jeannie Haak ◽  
Andrew M. Dylag ◽  
Michael A. O’Reilly
Keyword(s):  
Lung Disease ◽  
Influenza A ◽  
The Elderly ◽  
Virus Infections ◽  
Alveolar Epithelial ◽  
Mitochondrial Superoxide ◽  
Adult Mice ◽  
Club Cells ◽  
Age Dependent ◽  
Neonatal Hyperoxia

ABSTRACTThe severity of COVID-19 lung disease is higher in the elderly and people with pre-existing co-morbidities. People who were born preterm may be at greater risk for COVID-19 because their early exposure to oxygen at birth increases their risk of being hospitalized when infected with RSV and other respiratory viruses. Our prior studies in mice showed how high levels of oxygen (hyperoxia) between postnatal days 0-4 increases the severity of influenza A virus infections by reducing the number of alveolar epithelial type 2 (AT2) cells. Because AT2 cells express the SARS-CoV-2 receptors angiotensin converting enzyme (ACE2) and transmembrane protease/serine subfamily member 2 (TMPRSS2), we expected their expression would decline as AT2 cells were depleted by hyperoxia. Instead, we made the surprising discovery that expression of Ace2 and Tmprss2 mRNA increases as mice age and is accelerated by exposing mice to neonatal hyperoxia. ACE2 is primarily expressed at birth by airway Club cells and becomes detectable in AT2 cells by one year of life. Neonatal hyperoxia increases ACE2 expression in Club cells and makes it detectable in 2-month-old AT2 cells. This early and increased expression of SARS-CoV-2 receptors was not seen in adult mice who had been administered the mitochondrial superoxide scavenger mitoTEMPO during hyperoxia. Our finding that early life insults such as hyperoxia enhances the age-dependent expression of SARS-CoV-2 receptors in the respiratory epithelium helps explain why COVID-19 lung disease is greater in the elderly and people with pre-existing co-morbidities.

scholarly journals Neonatal hyperoxia enhances age-dependent expression of SARS-CoV-2 receptors in mice

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Min Yee ◽  
E. David Cohen ◽  
Jeannie Haak ◽  
Andrew M. Dylag ◽  
Michael A. O’Reilly
Keyword(s):  
Lung Disease ◽  
Influenza A ◽  
Viral Infections ◽  
The Elderly ◽  
Virus Infections ◽  
Mitochondrial Superoxide ◽  
Adult Mice ◽  
Club Cells ◽  
Age Dependent ◽  
Neonatal Hyperoxia

AbstractThe severity of COVID-19 lung disease is higher in the elderly and people with pre-existing co-morbidities. People who were born preterm may be at greater risk for COVID-19 because their early exposure to oxygen (hyperoxia) at birth increases the severity of respiratory viral infections. Hyperoxia at birth increases the severity of influenza A virus infections in adult mice by reducing the number of alveolar epithelial type 2 (AT2) cells. Since AT2 cells express the SARS-CoV-2 receptors angiotensin converting enzyme (ACE2) and transmembrane protease/serine subfamily member 2 (TMPRSS2), their expression should decline as AT2 cells are depleted by hyperoxia. Instead, ACE2 was detected in airway Club cells and endothelial cells at birth, and then AT2 cells at one year of age. Neonatal hyperoxia stimulated expression of ACE2 in Club cells and in AT2 cells by 2 months of age. It also stimulated expression of TMPRSS2 in the lung. Increased expression of SARS-CoV-2 receptors was blocked by mitoTEMPO, a mitochondrial superoxide scavenger that reduced oxidative stress and DNA damage seen in oxygen-exposed mice. Our finding that hyperoxia enhances the age-dependent expression of SARS-CoV-2 receptors in mice helps explain why COVID-19 lung disease is greater in the elderly and people with pre-existing co-morbidities.

scholarly journals Variation in senescent-dependent lung changes in inbred mouse strains

2007 ◽  
Vol 102 (4) ◽  
pp. 1632-1639 ◽  
Author(s):  
Kewu Huang ◽  
Wayne Mitzner ◽  
Richard Rabold ◽  
Brian Schofield ◽  
Hannah Lee ◽  
...  
Keyword(s):  
Gene Expression ◽  
Matrix Metalloproteinase ◽  
Inbred Mouse ◽  
Elastic Fiber ◽  
Lung Parenchyma ◽  
Inbred Strains ◽  
Lung Mechanics ◽  
Mouse Strains ◽  
Elastic Recoil ◽  
Age Dependent

Previous studies from our laboratories showed lung development differences between inbred strains of mice. In the present study, the C57BL/6J (B6) and DBA/2J (D2) strains were examined for senescent-dependent differences with respect to the lung structure and function. Specifically, we hypothesize that senescent changes in lung vary between strains due to identifiable gene expression differences. Quasi-static pressure-volume curves and respiratory impedance measurements were performed on 2- and 20-mo-old B6 and D2 mice. Lung volume at 30 cmH2O (V30) pressure was significantly ( P < 0.01) increased with age in both strains, but the increase was proportionally greater in D2 (68%) than in B6 (40%) mice. In addition, decreased elastic recoil pressure at 50% of V30 and a reduction in airway resistance as a function of positive end-expiratory pressure were observed in 20-mo-old D2 mice but not in B6 mice. Morphometric analysis of lung parenchyma showed significant decreases in elastic fiber content with age in both strains, but the collagen content was significantly ( P < 0.01) increased with age in D2 but not B6 mice at 20 mo. Furthermore, using quantitative RT-PCR methods, gene expression differences between strains suggested that D2 mice significantly ( P < 0.05) downregulated the expressions of elastin ( Eln) and procollagen I, III, and VI ( Col1a1, Col3a1, and Col6a3) in lung tissue at 20 mo of age. These age-dependent changes were accompanied by an increased gene expression in matrix metalloproteinase 9 ( Mmp9) in D2 and an increase in tissue inhibitor of matrix metalloproteinase ( Timp1 and Timp4) in B6 mice. In conclusion, the results from the present study demonstrate that lung mechanics of both strains show significant age-dependent changes. However, changes in D2 mice are accelerated relative to B6 mice. Moreover, gene expression differences appear to be involved in the strain-specific changes of lung mechanic properties.

Breathing at low lung volumes and chest strapping: a comparison of lung mechanics

1981 ◽  
Vol 50 (3) ◽  
pp. 650-657 ◽  
Author(s):  
N. J. Douglas ◽  
G. B. Drummond ◽  
M. F. Sudlow
Keyword(s):  
Lung Volume ◽  
Maximum Flow ◽  
Normal Subjects ◽  
Lung Mechanics ◽  
Lung Volumes ◽  
Flow Rates ◽  
Recoil Pressure ◽  
Forced Expiratory Flow ◽  
Expiratory Flow ◽  
Expiratory Flow Rates

In six normal subjects forced expiratory flow rates increased progressively with increasing degrees of chest strapping. In nine normal subjects forced expiratory flow rates increased with the time spent breathing with expiratory reserve volume 0.5 liters above residual volume, the increase being significant by 30 s (P less than 0.01), and flow rates were still increasing at 2 min, the longest time the subjects could breathe at this lung volume. The increase in flow after low lung volume breathing (LLVB) was similar to that produced by strapping. The effect of LLVB was diminished by the inhalation of the atropinelike drug ipratropium. Quasistatic recoil pressures were higher following strapping and LLVB than on partial or maximal expiration, but the rise in recoil pressure was insufficient to account for all the observed increased in maximum flow. We suggest that the effects of chest strapping are due to LLVB and that both cause bronchodilatation.

scholarly journals Longitudinal micro-CT provides biomarkers of lung disease that can be used to assess the effect of therapy in preclinical mouse models, and reveal compensatory changes in lung volume

2015 ◽  
Vol 9 (1) ◽  
pp. 91-98 ◽  
Author(s):  
Greetje Vande Velde ◽  
Jennifer Poelmans ◽  
Ellen De Langhe ◽  
Amy Hillen ◽  
Jeroen Vanoirbeek ◽  
...  
Keyword(s):  
Lung Disease ◽  
Mouse Models ◽  
Lung Volume ◽  
Micro Ct ◽  
Effect Of Therapy

Flow-Volume Curves in Infants with Lung Disease

PEDIATRICS ◽  
1983 ◽  
Vol 72 (4) ◽  
pp. 517-522
Author(s):  
S. Godfrey ◽  
E. Bar-Yishay ◽  
I. Arad ◽  
L. I. Landau ◽  
L. M. Taussig
Keyword(s):  
Lung Disease ◽  
Airway Obstruction ◽  
Lung Volume ◽  
Airway Resistance ◽  
Whole Body ◽  
Small Airways ◽  
Forced Expiration ◽  
Flow Volume ◽  
Complete Evaluation ◽  
Expiratory Flow

Partial expiratory flow-volume maneuvers have been performed on nine occasions on six infants with a variety of pulmonary problems using a new tech nique for thoracic compression. The infants were placed within an inflatable bag that was, itself, within a canvas bag. By sudden controlled inflation of the inner bag at end inspiration, partial expiratory flow-volume curves were generated and recorded by means of a face mask and pneumotachograph. By comparing these flow results with those airway resistance and lung volume measurements obtained from the infants in whole body plethysmography and by noting the effect of inhaling a helium/oxygen gas mixture, it was possible to partition the airway obstruction between large and small airways. The presence of small airway obstruction was noted in the absence of changes in airway resistance or lung volume in several instances. A complete evaluation of airway function should include this test of forced expiration for greater understanding and treatment of lung disease in infancy.

Rib cage and abdominal restrictions have different effects on lung mechanics

1980 ◽  
Vol 49 (6) ◽  
pp. 946-952 ◽  
Author(s):  
C. A. Bradley ◽  
N. R. Anthonisen
Keyword(s):  
Lung Volume ◽  
Total Lung Capacity ◽  
Lung Mechanics ◽  
Elastic Recoil ◽  
Rib Cage ◽  
Lung Capacity ◽  
Single Breath ◽  
Restrictive Procedures ◽  
Maximum Expiratory Flow ◽  
Per Se

The effects of a variety of restrictive procedures on lung mechanics were studied in eight healthy subjects. Rib cage restriction decreased total lung capacity (TLC) by 43% and significantly increased elastic recoil and maximum expiratory flow (MEF). Subsequent immersion of four subjects with rib cage restriction resulted in no further change in either parameter; shifts of blood volume did not reverse recoil changes during rib cage restriction. Abdominal restriction decreased TLC by 40% and increased MEF and elastic recoil, but recoil was increased significantly less than was the case with rib cage restriction. Further, at a given recoil pressure, MEF was less during rib cage restriction than during either abdominal restriction or no restriction. Measurements of the unevenness of inspired gas distribution by the single-breath nitrogen technique showed increased unevenness during rib cage restriction, which was significantly greater than that during abdominal restriction. We conclude that lung volume restriction induces changes in lung function, but the nature of these changes depends on how the restriction is applied and therefore cannot be ascribed to low lung volume breathing per se.

scholarly journals Mechanisms and consequences of oxidative stress in lung disease: therapeutic implications for an aging populace

2018 ◽  
Vol 314 (4) ◽  
pp. L642-L653 ◽  
Author(s):  
Louise Hecker
Keyword(s):  
Oxidative Stress ◽  
Lung Disease ◽  
Lung Diseases ◽  
The Elderly ◽  
Therapeutic Strategies ◽  
Rapid Expansion ◽  
Pulmonary Diseases ◽  
Normal Lung ◽  
Incidence And Mortality ◽  
And Oxidative Stress

The rapid expansion of the elderly population has led to the recent epidemic of age-related diseases, including increased incidence and mortality of chronic and acute lung diseases. Numerous studies have implicated aging and oxidative stress in the pathogenesis of various pulmonary diseases; however, despite recent advances in these fields, the specific contributions of aging and oxidative stress remain elusive. This review will discuss the consequences of aging on lung morphology and physiology, and how redox imbalance with aging contributes to lung disease susceptibility. Here, we focus on three lung diseases for which aging is a significant risk factor: acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD), and idiopathic pulmonary fibrosis (IPF). Preclinical and clinical development for redox- and senescence-altering therapeutic strategies are discussed, as well as scientific advancements that may direct current and future therapeutic development. A deeper understanding of how aging impacts normal lung function, redox balance, and injury-repair processes will inspire the development of new therapies to prevent and/or reverse age-associated pulmonary diseases, and ultimately increase health span and longevity. This review is intended to encourage basic, clinical, and translational research that will bridge knowledge gaps at the intersection of aging, oxidative stress, and lung disease to fuel the development of more effective therapeutic strategies for lung diseases that disproportionately afflict the elderly.

CLINICALAND ELECTROPHYSIOLOGICAL STUDY OF THE PERIPHERAL NERVOUS SYSTEM IN THE ELDERLY PEOPLE IN DARBHANGA

2021 ◽  
pp. 19-21
Author(s):  
Nutan Bala ◽  
Priyanka Priyanka ◽  
Sheela Kumari ◽  
Debarshi Jana
Keyword(s):  
Nervous System ◽  
Peripheral Nervous System ◽  
Linear Models ◽  
Electrophysiological Study ◽  
The Elderly ◽  
Elderly Subjects ◽  
Neurophysiological Studies ◽  
Age Dependent ◽  
Young Subjects ◽  
Effect Of Age

The effect of age on the peripheral nervous system was investigated by clinical examination and neurophysiological studies in 59 subjects aged 60- 103 years and 23 young subjects. Afull laboratory screen for factors which, though clinically silent, may constitute risk factors (RFs) for peripheral neuropathy was also performed in the elderly subjects. Our ndings show that the presence of RFs affects exceptionally the electrophysiological parameters in a statistically signicant way. The age-dependent changes in nerve conduction parameters were well predicted by non-linear models. The simultaneous electromyographical study demonstrates the re-innervation capacity of the motor system

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