{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T23:18:04Z","timestamp":1788909484120,"version":"build-2803163510"},"reference-count":90,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T00:00:00Z","timestamp":1772755200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p>Chronic obstructive pulmonary disease (COPD) is a common chronic condition characterized by chronic bronchitis and\/or emphysema with airflow obstruction, which can progress to cor pulmonale and respiratory failure. Associated with abnormal inflammatory responses to harmful gases and particulate matter, it carries high rates of disability and mortality, with a global prevalence among individuals aged 40 and older reaching 9%\u201310%. It is often regarded as a clinical and molecular model of accelerated lung aging. Age-related drift in immune function and metabolism plays a central part in this process, but how these changes are linked across different biological levels is still not fully clarified. Current work highlights mitochondrial injury and excessive reactive oxygen species as a central node that disrupts energy-sensing pathways, interferes with autophagy and epigenetic control, and weakens mitochondrial biogenesis, together fostering long-term glycolipid imbalance. At the same time, NF-\u03baB\u2013driven senescence-associated secretory activity and mitochondrial damage signals that engage the NLRP3 inflammasome form a reinforcing circuit that promotes macrophage dysfunction and exhaustion-like impairment of T and natural killer cells. These immune\u2013metabolic disturbances stabilize low-grade chronic inflammation and metabolic instability, helping to explain persistent inflammatory sequelae, airway remodeling, and progressive decline in lung function. Building on these insights, we discuss a translational path centered on composite biomarker panels that integrate immune-exhaustion signatures, senescence mediators, NAD+\u2013SIRT1 status, mitochondrial injury markers, and NLRP3 activity, and we consider low-intensity, multi-target therapeutic strategies designed to overcome the limitations of single-pathway treatments in COPD.<\/jats:p>","DOI":"10.3389\/fcell.2026.1756033","type":"journal-article","created":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T06:42:55Z","timestamp":1772779375000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Immune-metabolic positive feedback model in COPD: cross-mechanisms and potential intervention strategies"],"prefix":"10.3389","volume":"14","author":[{"given":"WenJing","family":"Chen","sequence":"first","affiliation":[{"name":"Southwest Medical University","place":["Luzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shi","family":"Huang","sequence":"additional","affiliation":[{"name":"Southwest Medical University","place":["Luzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijia","family":"He","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Zhou","sequence":"additional","affiliation":[{"name":"Southwest Medical University","place":["Luzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"RuiXiang","family":"Li","sequence":"additional","affiliation":[{"name":"Southwest Medical University","place":["Luzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guobing","family":"Wang","sequence":"additional","affiliation":[{"name":"Yibin Traditional Chinese Medicine Hospital","place":["Yibin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"753","DOI":"10.1038\/s41575-022-00658-y","article-title":"The metabolic nature of inflammatory bowel disease","volume":"19","author":"Adolph","year":"2022","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1186\/s13000-021-01184-2","article-title":"Identification of the most specific markers to differentiate primary pulmonary carcinoma from metastatic gastrointestinal carcinoma to the lung","volume":"17","author":"Alabdullah","year":"2022","journal-title":"Diagn. Pathol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1410","DOI":"10.1378\/chest.09-1850","article-title":"Systems biology approach to pulmonary diseases","volume":"137","author":"Auffray","year":"2010","journal-title":"Chest"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1451056","DOI":"10.3389\/fmed.2025.1451056","article-title":"Senolytic therapy reduces inflammation in epithelial cells from COPD patients and in smoke-exposure mice","volume":"12","author":"Baker","year":"2025","journal-title":"Front. Med."},{"key":"B5","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1007\/978-981-13-3681-2_3","article-title":"Pulmonary diseases and ageing","volume":"91","author":"Barnes","year":"2019","journal-title":"Subcell. Biochem."},{"key":"B6","doi-asserted-by":"publisher","first-page":"556","DOI":"10.1164\/rccm.201810-1975TR","article-title":"Cellular senescence as a mechanism in lung disease","volume":"200","author":"Barnes","year":"2019","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"B7","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1042\/CS20210900","article-title":"Autophagy in asthma and chronic obstructive pulmonary disease","volume":"136","author":"Barnes","year":"2022","journal-title":"Clin. Sci."},{"key":"B8","doi-asserted-by":"publisher","first-page":"917232","DOI":"10.3389\/fimmu.2022.917232","article-title":"Alveolar macrophages in early stage COPD show functional deviations with properties of impaired immune activation","volume":"13","author":"Bassler","year":"2022","journal-title":"Front. Immunol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"2072","DOI":"10.3390\/biomedicines11072072","article-title":"Airway epithelium senescence as a driving mechanism in COPD pathogenesis","volume":"11","author":"Bateman","year":"2023","journal-title":"Biomedicines"},{"key":"B10","doi-asserted-by":"publisher","first-page":"eaay8085","DOI":"10.1126\/science.aay8085","article-title":"Lipid droplets as innate immune hubs","volume":"370","author":"Bosch","year":"2020","journal-title":"Science"},{"key":"B11","doi-asserted-by":"publisher","first-page":"15625","DOI":"10.1073\/pnas.1906303116","article-title":"An immunometabolic pathomechanism for chronic obstructive pulmonary disease","volume":"116","author":"Bruzzaniti","year":"2019","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B12","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1186\/s12890-021-01582-8","article-title":"XIST promotes apoptosis and the inflammatory response in CSE-stimulated cells via the miR-200c-3p\/EGR3 axis","volume":"21","author":"Chen","year":"2021","journal-title":"BMC Pulm. Med."},{"key":"B13","doi-asserted-by":"publisher","first-page":"829","DOI":"10.1007\/s00011-023-01712-4","article-title":"Role of mitochondrial stress and the NLRP3 inflammasome in lung diseases","volume":"72","author":"Chen","year":"2023","journal-title":"Inflamm. Res."},{"key":"B14","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1186\/s12950-024-00384-z","article-title":"Fine particulate matter aggravates smoking induced lung injury via NLRP3\/caspase-1 pathway in COPD","volume":"21","author":"Chung","year":"2024","journal-title":"J. Inflamm."},{"key":"B15","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1164\/rccm.202012-4510OC","article-title":"Metformin: experimental and clinical evidence for a potential role in the treatment of chronic obstructive pulmonary disease","volume":"204","author":"Cleveland","year":"2021","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"B16","doi-asserted-by":"publisher","first-page":"3903","DOI":"10.3390\/ijms22083903","article-title":"Mitophagy in human diseases","volume":"22","author":"Doblado","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"B17","doi-asserted-by":"publisher","first-page":"6924","DOI":"10.3390\/ijms21186924","article-title":"Targeting aging pathways in COPD","volume":"21","author":"Easter","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"B18","doi-asserted-by":"publisher","first-page":"689866","DOI":"10.3389\/fimmu.2021.689866","article-title":"Neutrophil-dependent immunity during pulmonary infections and inflammations","volume":"12","author":"Effah","year":"2021","journal-title":"Front. Immunol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"882","DOI":"10.1016\/j.cell.2014.03.026","article-title":"Defective mitophagy in XPA via PARP-1 hyperactivation","volume":"157","author":"Fang","year":"2014","journal-title":"Cell"},{"key":"B20","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1186\/s12979-022-00267-y","article-title":"Age-associated T cell imbalance","volume":"19","author":"Fernandes","year":"2022","journal-title":"Immun. Ageing"},{"key":"B21","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1038\/s41392-025-02371-z","article-title":"Immunosenescence: signaling pathways, diseases and therapeutic targets","volume":"10","author":"Fu","year":"2025","journal-title":"Signal Transduct. Target. Ther."},{"key":"B22","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.pupt.2010.08.006","article-title":"Effects of inhaled corticosteroids in stable chronic obstructive pulmonary disease","volume":"24","author":"Glaab","year":"2011","journal-title":"Pulm. Pharmacol. Ther."},{"key":"B23","doi-asserted-by":"publisher","first-page":"426","DOI":"10.1080\/10409238.2021.1925217","article-title":"Cholesterol efflux pathways","volume":"56","author":"Groenen","year":"2021","journal-title":"Crit. Rev. Biochem. Mol. Biol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1038\/nrm.2017.95","article-title":"AMPK: guardian of metabolism","volume":"19","author":"Herzig","year":"2018","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"80","DOI":"10.12788\/fp.0459","article-title":"Clinical implications of a formulary conversion from budesonide\/formoterol to fluticasone\/salmeterol at a VA medical center","volume":"41","author":"Hoke","year":"2024","journal-title":"Fed. Pract."},{"key":"B64","doi-asserted-by":"publisher","first-page":"839","DOI":"10.1007\/s12272-021-01352-4","article-title":"Targeting fatty acid metabolism for fibrotic disorders","volume":"44","author":"Hwang","year":"2021","journal-title":"Archives Pharmacal Res."},{"key":"B26","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1016\/j.immuni.2013.08.001","article-title":"Mitochondrial cardiolipin is required for Nlrp3 inflammasome activation","volume":"39","author":"Iyer","year":"2013","journal-title":"Immunity"},{"key":"B27","doi-asserted-by":"publisher","first-page":"12017","DOI":"10.1073\/pnas.0705070104","article-title":"AMPK action in skeletal muscle","volume":"104","author":"J\u00e4ger","year":"2007","journal-title":"PNAS"},{"key":"B28","doi-asserted-by":"publisher","first-page":"298","DOI":"10.3390\/vaccines8020298","article-title":"Impact of influenza on pneumococcal vaccine effectiveness during Streptococcus pneumoniae infection in aged murine lung","volume":"8","author":"Jirru","year":"2020","journal-title":"Vaccines"},{"key":"B29","doi-asserted-by":"crossref","DOI":"10.1186\/s12979-022-00267-y","article-title":"Age-associated phenotypic imbalance in TCD4 and TCD8 cell subsets","volume":"19","author":"Fernandes","year":"2022","journal-title":"Immun. Ageing"},{"key":"B30","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1097\/MCP.0000000000000943","article-title":"Ageing and COPD: interrelationships","volume":"29","author":"Kakkera","year":"2023","journal-title":"Curr. Opin. Pulm. Med."},{"key":"B31","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1186\/1465-9921-14-30","article-title":"Apoptosis inhibitor of macrophage (AIM) expression in alveolar macrophages in COPD","volume":"14","author":"Kojima","year":"2013","journal-title":"Respir. Res."},{"key":"B32","doi-asserted-by":"publisher","first-page":"26","DOI":"10.3390\/pathophysiology32020026","article-title":"Linking lipid metabolism and immune function: new insights into chronic respiratory diseases","volume":"32","author":"Kotlyarov","year":"2025","journal-title":"Pathophysiology"},{"key":"B33","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1186\/s12931-019-0973-6","article-title":"Loss of the adhesion G-protein coupled receptor ADGRF5 in mice induces airway inflammation and expression of CCL2 in lung endothelial cells","volume":"20","author":"Kubo","year":"2019","journal-title":"Respir. Res."},{"key":"B34","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1165\/rcmb.2013-0382PS","article-title":"Senescence-associated secretory phenotype and its possible role in chronic obstructive pulmonary disease","volume":"51","author":"Kumar","year":"2014","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"1802460","DOI":"10.1183\/13993003.02460-2018","article-title":"Introduction to precision medicine in COPD","volume":"53","author":"Leung","year":"2019","journal-title":"Eur. Respir. J."},{"key":"B37","doi-asserted-by":"publisher","first-page":"1847","DOI":"10.2147\/COPD.S371801","article-title":"Inducible costimulator\u2013C-X-C motif chemokine receptor 3 signaling is involved in chronic obstructive pulmonary disease pathogenesis","volume":"17","author":"Li","year":"2022","journal-title":"Int. J. Chronic Obstr. Pulm. Dis."},{"key":"B38","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1186\/s12931-023-02634-9","article-title":"Role of mitochondrial fusion proteins MFN2 and OPA1 in lung cellular senescence in COPD","volume":"24","author":"Li","year":"2023","journal-title":"Respir. Res."},{"key":"B39","doi-asserted-by":"publisher","first-page":"814","DOI":"10.3390\/biomedicines12040814","article-title":"Mitochondrial dysfunction in chronic obstructive pulmonary disease","volume":"12","author":"Li","year":"2024","journal-title":"Biomedicines"},{"key":"B40","doi-asserted-by":"publisher","first-page":"2439","DOI":"10.1038\/s41401-022-00879-6","article-title":"Mitochondrial DAMPs amplify neuroinflammation","volume":"43","author":"Lin","year":"2022","journal-title":"Acta Pharmacol. Sin."},{"key":"B41","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1038\/s41580-019-0199-y","article-title":"mTOR at the nexus of nutrition and ageing","volume":"21","author":"Liu","year":"2020","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"2167","DOI":"10.2147\/COPD.S265728","article-title":"The role of mitophagy in COPD","volume":"15","author":"Liu","year":"2020","journal-title":"Int. J. Chronic Obstr. Pulm. Dis."},{"key":"B43","doi-asserted-by":"publisher","first-page":"100307","DOI":"10.1016\/j.labinv.2023.100307","article-title":"The role of mitochondrial quality control in chronic obstructive pulmonary disease","volume":"104","author":"Liu","year":"2024","journal-title":"Lab. Investig."},{"key":"B44","doi-asserted-by":"publisher","first-page":"804919","DOI":"10.3389\/fimmu.2021.804919","article-title":"Th17\/Treg imbalance in chronic obstructive pulmonary disease","volume":"12","author":"Louren\u00e7o","year":"2021","journal-title":"Front. Immunol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"115767","DOI":"10.1016\/j.ecoenv.2023.115767","article-title":"2-Deoxy-D-glucose ameliorates inflammation and fibrosis in silicosis","volume":"269","author":"Lu","year":"2024","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"B46","doi-asserted-by":"publisher","first-page":"1405","DOI":"10.1007\/s12079-023-00781-8","article-title":"Metformin + rapamycin ameliorates podocyte injury","volume":"17","author":"Ma","year":"2023","journal-title":"J. Cell Commun. Signal."},{"key":"B47","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1038\/s41588-022-01243-4","article-title":"Spatially resolved atlas of human lung","volume":"55","author":"Madissoon","year":"2023","journal-title":"Nat. Genet."},{"key":"B48","doi-asserted-by":"publisher","first-page":"7544","DOI":"10.1038\/s41598-022-11164-1","article-title":"Activation of NLRP3 inflammasome in stable chronic obstructive pulmonary disease","volume":"12","author":"Markeli\u0107","year":"2022","journal-title":"Sci. Rep."},{"key":"B49","doi-asserted-by":"publisher","first-page":"94","DOI":"10.15698\/cst2018.04.133","article-title":"New insights into the key role of HIF-1\u03b1 in IL-10-producing B cells","volume":"2","author":"Meng","year":"2018","journal-title":"Cell Stress"},{"key":"B50","doi-asserted-by":"publisher","first-page":"610","DOI":"10.1007\/s00018-022-04628-0","article-title":"Melatonin protects lung epithelial cells via SIRT3-dependent deacetylation of SOD2","volume":"79","author":"Ning","year":"2022","journal-title":"Cell. Mol. Life Sci."},{"key":"B51","doi-asserted-by":"publisher","first-page":"1772","DOI":"10.1038\/s43587-024-00758-1","article-title":"Nicotinamide riboside reduces airway inflammation in COPD","volume":"4","author":"Norheim","year":"2024","journal-title":"Nat. Aging"},{"key":"B52","doi-asserted-by":"publisher","first-page":"101679","DOI":"10.1016\/j.redox.2020.101679","article-title":"Complex interplay between autophagy and oxidative stress in the development of pulmonary disease","volume":"36","author":"Ornatowski","year":"2020","journal-title":"Redox Biol."},{"key":"B53","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/j.cmet.2014.12.005","article-title":"PKM2 regulates HIF-1\u03b1 and IL-1\u03b2 induction","volume":"21","author":"Palsson-McDermott","year":"2015","journal-title":"Cell Metab."},{"key":"B54","doi-asserted-by":"publisher","first-page":"3738","DOI":"10.3390\/ijms23073738","article-title":"Mitochondrial lipids","volume":"23","author":"Poulaki","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"B55","doi-asserted-by":"publisher","first-page":"1578","DOI":"10.1164\/ajrccm.163.7.2002015","article-title":"Defective natural killer and phagocytic activities in chronic obstructive pulmonary disease are restored by glycophosphopeptical","volume":"163","author":"Prieto","year":"2001","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"B56","doi-asserted-by":"publisher","first-page":"868086","DOI":"10.3389\/fmicb.2022.868086","article-title":"COPD and gut\u2013lung axis","volume":"13","author":"Qu","year":"2022","journal-title":"Front. Microbiol."},{"key":"B57","doi-asserted-by":"publisher","first-page":"918507","DOI":"10.3389\/fimmu.2022.918507","article-title":"Cigarette smoke-induced gasdermin D activation in chronic pulmonary inflammation and chronic obstructive pulmonary disease","volume":"13","author":"Quesniaux","year":"2022","journal-title":"Front. Immunol."},{"key":"B58","doi-asserted-by":"publisher","first-page":"3449","DOI":"10.3390\/jcm13123449","article-title":"Immunosenescence and inflammation in chronic obstructive pulmonary disease: a systematic review","volume":"13","author":"Ramos Jesus","year":"2024","journal-title":"J. Clin. Med."},{"key":"B59","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1016\/j.freeradbiomed.2021.02.018","article-title":"Oxidative stress-mediated AMPK inactivation determines the high susceptibility of LKB1-mutant NSCLC cells to glucose starvation","volume":"166","author":"Ren","year":"2021","journal-title":"Free Radic. Biol. Med."},{"key":"B60","doi-asserted-by":"publisher","first-page":"817","DOI":"10.3390\/medicina58060817","article-title":"Senescence: pathogenic driver in chronic obstructive pulmonary disease","volume":"58","author":"Rivas","year":"2022","journal-title":"Medicina (Kaunas)"},{"key":"B61","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1164\/rccm.202303-0507LE","article-title":"Spatial transcriptomics reveals B cell signature in COPD","volume":"209","author":"Rojas-Quintero","year":"2024","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"B62","doi-asserted-by":"publisher","first-page":"1089","DOI":"10.1111\/all.15977","article-title":"Metabolic pathways in immune senescence and inflammaging: novel therapeutic strategy for chronic inflammatory lung diseases","volume":"79","author":"Roth-Walter","year":"2024","journal-title":"Allergy"},{"key":"B63","doi-asserted-by":"publisher","first-page":"S266","DOI":"10.1513\/AnnalsATS.201808-585MG","article-title":"Mitochondrial dysfunction in chronic lung diseases","volume":"15","author":"Ryter","year":"2018","journal-title":"Ann. Am. Thorac. Soc."},{"key":"B65","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1080\/17476348.2023.2205127","article-title":"Impact of aging on immune function in the pathogenesis of pulmonary diseases","volume":"17","author":"Shaikh","year":"2023","journal-title":"Expert Rev. Respir. Med."},{"key":"B66","doi-asserted-by":"publisher","first-page":"5555","DOI":"10.1038\/s41598-020-62272-9","article-title":"Enhanced glycolysis in adipose tissue macrophages","volume":"10","author":"Sharma","year":"2020","journal-title":"Sci. Rep."},{"key":"B83","doi-asserted-by":"publisher","first-page":"330","DOI":"10.2478\/jtim-2022-0019","article-title":"Mitochondrial damage-associated molecular patterns in COPD","volume":"11","author":"Shen","year":"2022","journal-title":"J. Transl. Intern. Med."},{"key":"B67","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1016\/j.immuni.2012.01.009","article-title":"Oxidized mitochondrial DNA activates the NLRP3 inflammasome during apoptosis","volume":"36","author":"Shimada","year":"2012","journal-title":"Immunity"},{"key":"B68","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1084\/jem.20150900","article-title":"PKM2 bridges metabolic and inflammatory dysfunction","volume":"213","author":"Shirai","year":"2016","journal-title":"J. Exp. Med."},{"key":"B69","doi-asserted-by":"publisher","first-page":"881","DOI":"10.3390\/cells13100881","article-title":"NADH intraperitoneal injection prevents lung inflammation in a BALB\/C mice model of cigarette smoke-induced chronic obstructive pulmonary disease","volume":"13","author":"Slama","year":"2024","journal-title":"Cells"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1183\/16000617.0165-2020","article-title":"Mitochondrial dysfunction in lung ageing and disease","volume":"29","author":"Sm","year":"2020","journal-title":"Eur. Respir. Rev."},{"key":"B71","doi-asserted-by":"publisher","first-page":"1990","DOI":"10.1161\/ATVBAHA.120.314037","article-title":"Metabolic reprogramming in immune response and tissue inflammation","volume":"40","author":"Sun","year":"2020","journal-title":"Arteriosclerosis, Thrombosis, Vasc. Biol."},{"key":"B72","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1038\/s41577-019-0165-0","article-title":"The NLRP3 inflammasome: molecular activation and regulation to therapeutics","volume":"19","author":"Swanson","year":"2019","journal-title":"Nat. Rev. Immunol."},{"key":"B73","doi-asserted-by":"publisher","first-page":"53","DOI":"10.3390\/biomedicines9010053","article-title":"Orchestration of neutrophil extracellular traps during chronic obstructive pulmonary disease development","volume":"9","author":"Trivedi","year":"2021","journal-title":"Biomedicines"},{"key":"B74","doi-asserted-by":"publisher","first-page":"4988","DOI":"10.1038\/s41467-024-49282-1","article-title":"Immunological synapse formation between T regulatory cells and cancer-associated fibroblasts promotes tumour development","volume":"15","author":"Varveri","year":"2024","journal-title":"Nat. Commun."},{"key":"B75","doi-asserted-by":"publisher","first-page":"2571","DOI":"10.4049\/jimmunol.1701681","article-title":"MTOR suppresses cigarette smoke\u2013induced epithelial cell death and airway inflammation in chronic obstructive pulmonary disease","volume":"200","author":"Wang","year":"2018","journal-title":"J. Immunol."},{"key":"B76","doi-asserted-by":"publisher","first-page":"1383503","DOI":"10.3389\/fimmu.2024.1383503","article-title":"The aging lung: microenvironment, mechanisms, and diseases","volume":"15","author":"Wang","year":"2024","journal-title":"Front. Immunol."},{"key":"B77","doi-asserted-by":"publisher","first-page":"e77457","DOI":"10.7554\/eLife.77457","article-title":"HIF-1\u03b1 induces glycolytic reprograming in alveolar macrophages","volume":"11","author":"Woods","year":"2022","journal-title":"eLife"},{"key":"B78","doi-asserted-by":"publisher","first-page":"4816","DOI":"10.21037\/jtd.2019.10.26","article-title":"Extracellular mtDNA activates NLRP3 and induces acute lung injury","volume":"11","author":"Wu","year":"2019","journal-title":"J. Thorac. Dis."},{"key":"B79","doi-asserted-by":"publisher","first-page":"6899","DOI":"10.2147\/IJGM.S527733","article-title":"Threshold-triggered immune dysregulation precedes clinical COPD: a stage-specific diagnostic model combining cytokine profiling and lymphocyte phenotyping","volume":"18","author":"Wu","year":"2025","journal-title":"Int. J. General Med."},{"key":"B80","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1038\/s41392-020-00311-7","article-title":"NAD+ metabolism: pathophysiologic mechanisms and therapeutic potential","volume":"5","author":"Xie","year":"2020","journal-title":"Signal Transduct. Target. Ther."},{"key":"B81","doi-asserted-by":"publisher","first-page":"588522","DOI":"10.3389\/fimmu.2020.588522","article-title":"Cigarette smoke-induced lymphoid neogenesis in COPD involves IL-17\/RANKL pathway","volume":"11","author":"Xiong","year":"2020","journal-title":"Front. Immunol."},{"key":"B82","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1186\/s12931-024-02847-6","article-title":"PD-1+ T lymphocyte proportions and hospitalized exacerbation of COPD: a prospective cohort study","volume":"25","author":"Xue","year":"2024","journal-title":"Respir. Res."},{"key":"B84","doi-asserted-by":"publisher","first-page":"1947","DOI":"10.1016\/j.biomaterials.2008.12.044","article-title":"Porous PLGA microparticles for pulmonary drug delivery","volume":"30","author":"Yang","year":"2009","journal-title":"Biomaterials"},{"key":"B85","doi-asserted-by":"publisher","first-page":"e200026","DOI":"10.20900\/immunometab20200026","article-title":"Macrophage immunometabolism and inflammaging","volume":"2","author":"Yarbro","year":"2020","journal-title":"Immunometabolism"},{"key":"B86","doi-asserted-by":"publisher","first-page":"7582980","DOI":"10.1155\/2020\/7582980","article-title":"Sirtuin 3 inhibits airway epithelial oxidative stress in cigarette smoke-induced COPD","volume":"2020","author":"Zhang","year":"2020","journal-title":"Oxidative Med. Cell. Longev."},{"key":"B87","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1186\/s12931-021-01707-x","article-title":"Plasma mtDNA and COPD progression","volume":"22","author":"Zhang","year":"2021","journal-title":"Respir. Res."},{"key":"B88","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1186\/s12931-022-01986-y","article-title":"Roles of sirtuin family members in chronic obstructive pulmonary disease","volume":"23","author":"Zhang","year":"2022","journal-title":"Respir. Res."},{"key":"B89","doi-asserted-by":"publisher","first-page":"1514686","DOI":"10.3389\/fmed.2025.1514686","article-title":"Knowledge mapping of autophagy in chronic obstructive pulmonary disease from 2004 to 2024: a bibliometric analysis","volume":"12","author":"Zhang","year":"2025","journal-title":"Front. Med."},{"key":"B90","doi-asserted-by":"publisher","first-page":"1004275","DOI":"10.3389\/fphys.2022.1004275","article-title":"The interplay between oxidative stress and autophagy in chronic obstructive pulmonary disease","volume":"13","author":"Zhao","year":"2022","journal-title":"Front. Physiol."},{"key":"B91","doi-asserted-by":"publisher","first-page":"661","DOI":"10.18632\/aging.100685","article-title":"Role of mitochondrial reactive oxygen species in age-related inflammatory activation of endothelium","volume":"6","author":"Zinovkin","year":"2014","journal-title":"Aging"}],"container-title":["Frontiers in Cell and Developmental Biology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2026.1756033\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T06:42:56Z","timestamp":1772779376000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2026.1756033\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,6]]},"references-count":90,"alternative-id":["10.3389\/fcell.2026.1756033"],"URL":"https:\/\/doi.org\/10.3389\/fcell.2026.1756033","relation":{},"ISSN":["2296-634X"],"issn-type":[{"value":"2296-634X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,6]]},"article-number":"1756033"}}