American journal of physiology. Lung cellular and molecular physiology最新文献

{"title":"V̇co₂: the essential underpinning to homeostatic control of breathing.","authors":"Jerome A Dempsey, Donald R McCrimmon","doi":"10.1152/ajplung.00141.2026","DOIUrl":"10.1152/ajplung.00141.2026","url":null,"abstract":"<p><p>This essay addresses the fundamental mechanism underlying the precise regulation of [Formula: see text] during steady states of air-breathing eupnea and hyperpnea. First, an argument is made for CO₂/H⁺ chemoreception as an important compensatory feedback regulator of breathing and breathing stability, especially during nonrapid eye movement (NREM) sleep. Tonic contributions to respiratory drive occur from the carotid chemoreceptors and retrotrapezoid nucleus (RTN). A case against chemoreception of Pco₂ as the primary homeostatic [Formula: see text] regulator is made based on conditions where precise [Formula: see text] control during air-breathing exists even when ventilatory responsiveness to raised Pco₂ is markedly subnormal or when a measurable [Formula: see text] error signal is nonexistent. Alternatively, a case is made that homeostatic ventilatory control incorporates information critically dependent on pulmonary CO₂ exchange, as revealed when: <i>1</i>) V̇co₂, per se, is altered at rest or exercise; <i>2</i>) V_d/V_T is raised or lowered; and <i>3</i>) the resting [Formula: see text] set point is changed, thereby changing respiratory system plant gains. In each of these common conditions, substantial ventilatory adjustments occur to achieve near-proportional V̇a:V̇co₂ linkages at rest and/or exercise with no coincidence changes in CO₂ chemoreception. We view this V̇co₂-mediated mechanism as a dedicated tracking system for alveolar ventilation that provides an essential underpinning in a traditional hybrid model of homeostatic ventilatory control. Although some potential mediators of these V̇co₂ effects have been suggested, such as an integrative role for the RTN, they remain inadequately explored. It is time to restart enquiry, using modern neuroscience approaches, into the mediation of V̇co₂ as the critical underpinning to [Formula: see text] homeostasis.</p>","PeriodicalId":7593,"journal":{"name":"American journal of physiology. Lung cellular and molecular physiology","volume":" ","pages":"L34-L47"},"PeriodicalIF":3.8,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148148160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The right time, the right cell: the potential for precision senotherapy in pulmonary arterial hypertension.","authors":"Kellen Hirsch, Andrew G Horn, Anthony J Donato, Kiana M Schulze","doi":"10.1152/ajplung.00104.2026","DOIUrl":"10.1152/ajplung.00104.2026","url":null,"abstract":"<p><p>Pulmonary arterial hypertension (PAH) is a fatal vasculopathy driven by proinflammatory signaling that leads to pulmonary vascular remodeling and ultimately, right ventricular failure. Existing therapies fail to eliminate dysfunctional cells or reverse pathologic remodeling. Cellular senescence, a state of persistent cell-cycle arrest coupled with proinflammatory signaling, has emerged as a compelling, yet complex, contributor to PAH pathophysiology. Human data indicate that senescent cells accumulate within remodeled pulmonary vascular lesions and may promote proliferation and apoptosis resistance in neighboring cells. However, preclinical studies testing senolytic therapies in PAH have yielded conflicting results, raising uncertainty about their translational potential. This review will synthesize the current literature regarding cellular senescence in PAH and propose that heterogeneity in <i>1</i>) senescent cell type, <i>2</i>) senolytic mechanisms and off-target susceptibility, and <i>3</i>) the disease stage at the time of intervention can help explain divergent outcomes. By addressing these three key points, this review will identify practical considerations for advancing \"precision senotherapy\" in PAH, including dosing strategies favoring intermittent, short-course senolytic regimens, and combination treatment approaches. Together, these concepts provide a framework for designing safer, stage-aware, cell-informed senotherapeutic studies in PAH.</p>","PeriodicalId":7593,"journal":{"name":"American journal of physiology. Lung cellular and molecular physiology","volume":" ","pages":"L661-L669"},"PeriodicalIF":3.8,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13202487/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147759899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Call for Papers: Cystic fibrosis and other lung diseases in the CFTR modulator era.","authors":"Rodney D Britt, Wolfgang M Kuebler","doi":"10.1152/ajplung.00016.2026","DOIUrl":"10.1152/ajplung.00016.2026","url":null,"abstract":"","PeriodicalId":7593,"journal":{"name":"American journal of physiology. Lung cellular and molecular physiology","volume":" ","pages":"L670-L672"},"PeriodicalIF":3.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147759856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AlveolEye: rapid and precise lung morphometry guided by computer vision.","authors":"Joseph Hirsh, Samuel Hirsh, Shawyon P Shirazi, James Hirsh, Imani Douglas, Shriya Garg, Yeongseo Son, Arline Pierre-Louis, Claire Bunn, Christopher S Jetter, Taiana J James, Alexandria L Sharkey, John T Benjamin, Jason J Gokey, Akihiro Ochi, Jeff Reese, Marilyn B Renfree, Geoffrey Shaw, Jonathan A Kropski, Jennifer M S Sucre, Nicholas M Negretti","doi":"10.1152/ajplung.00337.2025","DOIUrl":"10.1152/ajplung.00337.2025","url":null,"abstract":"<p><p>Rigorous and reproducible evaluation of lung tissue under different conditions is necessary to interpret development, injury, and pharmacologic interventions. Common histological measurements in the distal lung include mean linear intercept (MLI) as a metric of alveolarization and airspace volume density (ASVD) as a metric of airspaces relative to tissue. Historically, these have been performed manually in a time-intensive process, with reproducible trends but a high degree of variability between individuals. To improve the reproducibility and throughput of lung morphometry, we developed AlveolEye, an open-source, semiautomated, computer vision-assisted tool that rapidly and reproducibly calculates MLI and ASVD from images of standard hematoxylin and eosin-stained tissue sections. AlveolEye-assisted MLI calculation closely aligns with manually derived measurements for corresponding images, with preservation of trends in measurements between noninjured controls and neonatal mice subjected to two different injury models. Analyzing human tissue of varying ages suggests that the approach developed in AlveolEye is generalizable across species. Notably, AlveolEye markedly reduced the average variation across individual analyzers, with the greatest improvement in precision among individuals with the least experience in performing lung morphometry. The design of AlveolEye is intentionally semiautomated, preserving the investigator's ability to assess and adjust parameters based on sample characteristics. AlveolEye facilitates efficient lung morphological measurements on larger sample sizes, allowing for greater statistical power for preclinical studies, and improves precision across individual observers, allowing for improved rigor in experimental design and execution.<b>NEW & NOTEWORTHY</b> Calculating lung morphometric measurements is time-intensive, with a high degree of interrater variability. We developed a semiautomated tool, AlveolEye, which uses computer vision to perform rapid and precise lung morphometry, reducing variability and improving efficiency. AlveolEye presents an opportunity for improved rigor, efficiency, and reproducibility in studies of lung development, injury, and regeneration.</p>","PeriodicalId":7593,"journal":{"name":"American journal of physiology. Lung cellular and molecular physiology","volume":" ","pages":"L755-L766"},"PeriodicalIF":3.8,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13296161/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147809702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The pyruvate kinase activator etavopivat (FT-4202) limits pulmonary and systemic sequelae of sepsis in a mouse LPS model.","authors":"Youwei Chen, Hongmei Zhu, Lisheng Zhang, Weijia Mai, Shein-Chung Chow, Desmond Wai Loon Chin, Sylvie Guichard, Marcus Carden, Apoorva Jagadish, Rodolfo A Estupinan, Ian Welsby, Timothy J McMahon","doi":"10.1152/ajplung.00389.2025","DOIUrl":"10.1152/ajplung.00389.2025","url":null,"abstract":"<p><p>Sepsis is frequently characterized by abnormal O₂ uptake by red blood cells (RBCs) in the lung and/or dysregulated tissue O₂ delivery by RBCs. New approaches are needed to improve O₂ transport and clinical outcomes in sepsis with or without anemia. FT-4202 (etavopivat) is an allosteric RBC pyruvate kinase (PKR) activator (PKRA) previously shown to increase RBC ATP and decrease 2,3-bisphosphoglycerate (2,3-BPG), a negative allosteric effector of O₂-binding by hemoglobin. We hypothesized that PKR activation could mitigate lipopolysaccharide (LPS)-induced sepsis/acute lung injury (ALI) by preserving ATP and/or lowering BPG levels to promote O₂ uptake. We measured systemic (body weight change, cytokines), renal/inflammatory (neutrophil gelatinase-associated lipocalin; NGAL), and respiratory responses to LPS ± FT-4202. FT-4202 protected mice from LPS-induced weight loss but not hypoxemia. LPS-induced increases in albumin and neutrophilic myeloperoxidase (MPO) in mouse bronchoalveolar lavage fluid were significantly blunted in mice pretreated with FT-4202. FT-4202 attenuated LPS-induced elevations in the proinflammatory cytokines IFN-γ, IL-6, and TNF-α. FT-4202 attenuated LPS-induced elevations in the acute kidney injury (and/or inflammatory) marker NGAL. In RBCs from healthy mice, ex vivo FT-4202 treatment significantly increased intra-RBC ATP and ATP export. We conclude that the PKRA FT-4202 protected against systemic and respiratory (capillary permeability and neutrophil influx) features of sepsis induced by LPS in mice. FT-4202 promoted RBC ATP generation and export ex vivo, which could contribute to the favorable effects in LPS-induced sepsis.<b>NEW & NOTEWORTHY</b> Etavopivat (FT-4202), a RBC-selective pyruvate kinase activator (PKRA), limited weight loss, inflammatory cytokines, neutrophil gelatinase-associated lipocalin (NGAL) elevation, and neutrophilia in a mouse sepsis model. We show for the first time that a PKRA promotes ATP export from mouse RBCs, and this could contribute to the benefits of this RBC-directed therapeutic.</p>","PeriodicalId":7593,"journal":{"name":"American journal of physiology. Lung cellular and molecular physiology","volume":" ","pages":"L673-L684"},"PeriodicalIF":3.8,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13142219/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147669922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural and molecular alterations in lung lymphatic endothelial cells induced by cigarette smoking: insights and emerging hypotheses for vaping.","authors":"Hoda Rahimi, Jiwon Hong, Victor Maldonado Zimbron, Anthony Phillips, Kelly Burrowes","doi":"10.1152/ajplung.00340.2025","DOIUrl":"10.1152/ajplung.00340.2025","url":null,"abstract":"<p><p>Pulmonary lymphatics play multiple essential roles in lung homeostasis through interstitial fluid removal, traffic of immune cells, and antigen presentation. This highly branching vascular bed comprises initial capillaries, pre-collecting vessels, and collecting lymphatics, and it is lined by characteristic lymphatic endothelial cells (LECs). These cells are distinct from blood endothelial cells in their structure, molecular markers (e.g., PROX1, LYVE-1, VEGFR-3), and responsiveness to inflammatory and mechanical stimuli. In health, LECs preserve barrier integrity, promote immune surveillance, and support unidirectional lymph flow. However, during pulmonary inflammation or injury, LECs may undergo phenotypic changes that impair function and promote local coagulation. This review consolidates current knowledge on pulmonary lymphatic vessel structure and function and LEC biology, with a focus on their involvement in inflammation and coagulation pathways. We examine how cigarette smoke disrupts LEC homeostasis, leading to endothelial injury, procoagulant factor upregulation [e.g., tissue factor, plasminogen activator inhibitor-1 (PAI-1)], and fibrin-rich thrombosis in lung lymphatics. Although vaping induces oxidative stress and vascular inflammation, its effects on the pulmonary lymphatic system have not been clearly explained. Based on pathological features shared with smoking, we propose potential mechanisms by which e-cigarette aerosols may contribute to lymphatic endothelial dysfunction and altered coagulation in lungs. Given the increasing prevalence of vaping, further research using in vitro, in vivo, and human studies is needed to elucidate how inhaled toxicants alter LEC function and to identify novel targets for preserving lymphatic health in lung disease.</p>","PeriodicalId":7593,"journal":{"name":"American journal of physiology. Lung cellular and molecular physiology","volume":" ","pages":"L634-L652"},"PeriodicalIF":3.8,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147697144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Considerations for early life genetic therapies in cystic fibrosis.","authors":"Ashley L Cooney, Ian M Thornell, Alejandro A Pezzulo, Anthony J Fischer, Daniel P Cook, Mahmoud H Abou Alaiwa, Katie M Larson Ode, Aliye Uc, Joseph Zabner, Amy L Ryan, David A Stoltz, Patrick L Sinn, Paul B McCray, David K Meyerholz","doi":"10.1152/ajplung.00022.2026","DOIUrl":"10.1152/ajplung.00022.2026","url":null,"abstract":"<p><p>Cystic fibrosis (CF) is caused by mutations in the gene encoding for the CF transmembrane conductance regulator (CFTR) anion channel. Since the initial characterization of CF in the early 20th century, advances in clinical management have reduced disease burden and increased longevity. These advances are amplified by the recent development of highly effective CFTR modulator therapies (HEMTs) that have provided remarkable clinical results in people with CF (pwCF). However, some pwCF do not benefit from HEMT due to several limiting factors. Genetic therapies have increasingly emerged as prospective, complementary treatments to HEMTs for those unable to benefit from HEMTs. Genetic therapies have yet to be approved for clinical use in pwCF, but multiple clinical trials are in progress. In anticipation of future approval of one or more of these candidates, it is essential to identify and discuss how these genetic therapies might be used in early life, when many CF lesions originate, especially for those with severe mutations. In this multidisciplinary review, we discuss several pertinent factors such as CFTR localization and function, CF disease origins, emerging developments in genetic therapies, ethical considerations, and other perspectives needed to guide future genetic therapies in early life.</p>","PeriodicalId":7593,"journal":{"name":"American journal of physiology. Lung cellular and molecular physiology","volume":" ","pages":"L737-L754"},"PeriodicalIF":3.8,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13262679/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147759931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tracheal aspirates of mechanically ventilated preterm infants possess cytopathic tau variants: a prospective exploratory study.","authors":"Kalsang Dolma, Saminathan Anbalagan, Linn Ayers, Althea deWeever, Brian W Fouty, Jonathon P Audia, Chung-Sik Choi, Mike T Lin, Manimaran Ramani, Troy Stevens","doi":"10.1152/ajplung.00012.2026","DOIUrl":"10.1152/ajplung.00012.2026","url":null,"abstract":"<p><p>Tau protein, a microtubule-associated protein expressed in lung capillary endothelium, is detectable early in lung development and has been implicated in systemic dysfunction during adult respiratory infections. Its role in neonatal lung injury, however, remains undefined. In this study, we analyzed tracheal aspirates from 67 mechanically ventilated infants (51 preterm and 16 term) and compared them with 20 cord blood samples and five healthy adult plasma samples. Preterm infants were further stratified by histological chorioamnionitis status and severity of bronchopulmonary dysplasia (BPD) at 36-wk postmenstrual age (Jensen's 2019 criteria). Total tau concentrations were measured using a Meso Scale Discovery assay, and neuronal tau seeding assays assessed the presence of cytopathic tau variants. Tau was detected in all samples, with significantly higher concentrations in neonatal tracheal aspirates and cord blood compared with adult plasma. In both cord blood and tracheal aspirates, preterm infants exhibited elevated total tau levels relative to term infants. The tau protein present in preterm tracheal aspirates induced neuronal tau aggregation across gestational ages. Although total tau concentrations did not differ, the cytopathic activity of tracheal aspirates was increased in infants with chorioamnionitis. Neither total tau nor seeding activity correlated with BPD severity. Our study findings demonstrate that tau is abundant in the airways of mechanically ventilated preterm infants and exhibits cytopathic properties, suggesting a potential role in both neonatal lung injury and development. Further studies are needed to clarify the mechanistic contribution of tau to lung pathology in this highly vulnerable population.<b>NEW & NOTEWORTHY</b> In mechanically ventilated preterm infants, endogenous airway molecules may influence lung injury and development. Tau, a microtubule-associated protein expressed in lung endothelium, was abundant in neonatal tracheal aspirates and elevated in preterm infants. Tau in preterm samples also showed cytopathic seeding activity, which was further increased in infants with histological chorioamnionitis. These findings identify tau as a previously unrecognized bioactive airway component that may contribute to early lung pathology.</p>","PeriodicalId":7593,"journal":{"name":"American journal of physiology. Lung cellular and molecular physiology","volume":" ","pages":"L780-L788"},"PeriodicalIF":3.8,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13308501/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147980219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating human lung resilience, its evolutionary history and its relation to COPD.","authors":"Isabelle Dupin, Maël Lemoine","doi":"10.1152/ajplung.00312.2025","DOIUrl":"10.1152/ajplung.00312.2025","url":null,"abstract":"<p><p>A subset of long-term smokers remain free of chronic obstructive pulmonary disease or lung cancer, a phenomenon termed \"lung resilience.\" Understanding this resilience could reveal protective mechanisms that preserve respiratory health, yet conceptual and methodological precision is required. Importantly, resilience is not merely the inverse of vulnerability, but a process that can be investigated in its own. In this review, we clarify this concept of resilience and its distinction from tolerance and resistance, and situate human lung resilience within a cross-organ and cross-species framework. We also critically assess the hypothesis that evolutionary processes may have influenced human resilience to smoke exposure. Finally, we advocate for rigorous clinical phenotyping and mechanistic approaches to dissect the interplay between genetics, physiology, and evolution. A refined conceptual framework will establish resilience as a productive paradigm in respiratory medicine, with potential to advance our understanding of disease susceptibility and to inform novel therapeutic strategies.</p>","PeriodicalId":7593,"journal":{"name":"American journal of physiology. Lung cellular and molecular physiology","volume":" ","pages":"L625-L633"},"PeriodicalIF":3.8,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7619105/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147687564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Age-related changes in respiratory system mechanics and lung morphometry.","authors":"Szonja Decker, Obaid U Khurram, Carlos B Mantilla, Gary C Sieck","doi":"10.1152/ajplung.00341.2025","DOIUrl":"10.1152/ajplung.00341.2025","url":null,"abstract":"<p><p>Aging leads to degenerative changes in lung structural and mechanical properties that may impact breathing. Relatively little is known about how age-related alterations in lung mechanical properties impact expiratory duration (<i>T</i>_E) and residual volume (RV). The present study tested three hypotheses: <i>1</i>) alveolar airspace increases with age due to alveolar wall breakdown, <i>2</i>) lung elastic recoil decreases, slowing expiratory flow (E-flow), and <i>3</i>) airway compliance (<i>C</i>_aw) decreases, promoting air trapping reflected by increased RV. To test these hypotheses, we evaluated changes in alveolar size using histological assessments, mechanical properties using forced oscillation perturbations with a programmable mechanical ventilator and breathing parameters using plethysmography in young (6 mo) and old (24 mo) Fischer 344 rats. Mean linear intercept (<i>L</i>_m) was higher in old (65 ± 10 µm) compared with young (55 ± 5 µm) rats, indicating alveolar airspace increase. In old rats, decreased elastic recoil was indicated by increased parameter <i>K</i> (0.178 ± 0.010 vs. 0.167 ± 0.013 in young) and higher V₁₀/total lung capacity (TLC) (80.7 ± 1.2% vs. 78.5 ± 2.5% in young). In addition, RV was higher in old rats (0.41 ± 0.10 mL vs. 0.27 ± 0.05 mL in young), consistent with air trapping. These mechanical changes were associated with increased E-flow (∼30%) in old rats, attributable to increased tidal volume (2.08 ± 0.41 mL vs. 1.53 ± 0.36 mL in young) as <i>T</i>_E was unchanged. These results indicate important changes in the lung parenchyma, causing alteration in passive and active properties of the respiratory system in aging rats.<b>NEW & NOTEWORTHY</b> The present study provides novel physiological insights into aging by measuring airway compliance and residual volume via forced oscillation perturbations using a programmable mechanical ventilator (flexiVent-currently considered a gold standard for in vivo lung function measurements). In addition, dynamic measurements of lung inflation reported herein may serve as early indicators of altered elastic properties. Taken together, the findings offer a comprehensive assessment of age-related changes in lung structure and function.</p>","PeriodicalId":7593,"journal":{"name":"American journal of physiology. Lung cellular and molecular physiology","volume":" ","pages":"L685-L695"},"PeriodicalIF":3.8,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13227697/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147809680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}