Chronic lung diseases—including chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), obstructive sleep apnea (OSA), asthma, bronchiectasis, and lung cancer—are intimately linked to the aging process. They carry a high global burden and remain notoriously difficult to treat. EVs have been established as fundamental, shared players in the pathogenesis of diverse senescence-associated lung diseases which play crucial roles in modulating cellular senescence by transmitting senescent signals, modulating immune-inflammatory responses, regulating gene expression and cell function, altering intracellular environments, and serving as potential therapeutic targets.
To systematically synthesize this rapidly evolving field, a team led by Professor Wang Ruiying from Shanxi Bethune Hospital, together with Professor Chen Yahong from Peking University Third Hospital, Professor Liu Xiansheng from Tongji Hospital, and Professor Peter J. Barnes from Imperial College London, compiled a comprehensive review entitled “Insights into extracellular vesicles in senescence-associated chronic lung diseases”. Their findings were published in the Chinese Medical Journal on July 13, 2026.
“Cellular senescence is a major driver of many chronic pulmonary conditions, and EVs act as essential shuttles that propagate senescence signals between cells,” explains Prof. Wang, the first author. EVs exert distinct effects under different disease conditions. Under healthy conditions, EVs help maintain tissue homeostasis, regulate immune responses and cell proliferation, and repair. However, in disease states, senescent cells release EVs with a distinct, pro-senescent payload. When taken up by neighboring healthy cells, these EVs can induce secondary senescence, creating a vicious cycle that amplifies inflammation, tissue damage, and fibrosis.
The review highlights multiple mechanistic pathways through which EVs drive the progression of senescence-associated lung diseases. They facilitate aberrant intercellular communication, deliver pathogenic miRNAs and proteins, promote chronic inflammation, modulate immune cell function, amplify oxidative stress, and actively contribute to extracellular matrix remodeling. The various contents in EVs, particularly microRNAs (miRNAs), regulate aging through several mechanisms. miR-34a, miR-21, miR-125a-5p, miR-146a-5p, and miR-570-3p have been shown to target key anti-aging molecules such as sirtuins (SIRT), thereby accelerating epithelial and fibroblast senescence. In COPD, for instance, small EVs from airway epithelial cells transfer miR‑34a to suppress SIRT1, increasing p21 expression and senescence markers in recipient cells. In IPF, fibroblast-derived EVs deliver miR‑23b‑3p and miR‑494‑3p, which downregulate SIRT3 and trigger mitochondrial dysfunction, reinforcing the pro-fibrotic, pro-senescent microenvironment. EV-mediated alterations in miR-34a may concurrently influence both immune polarization and cellular aging pathways in the asthmatic airway. Additionally, sputum miR-92b-5p and miR-223-3p may directly link Pseudomonas aeruginosa colonization to the airway aging process in bronchiectasis by mediating local inflammation (IL-1β/IL-8) and regulating longevity-related pathways. In OSA, EVs are associated with cardiovascular and neurocognitive complications. In lung cancer, EVs remodel the tumor microenvironment and mediate therapeutic resistance. Such functional diversity underscores the pivotal role of EVs in the regulatory network of pulmonary diseases.
Given their inherent biocompatibility and targeted delivery capacity, EVs have emerged as promising therapeutic agents. Mesenchymal stem cell-derived EVs have demonstrated the potential to alleviate inflammation, downregulate senescence markers, and repair lung tissues in COPD and IPF models. Neutrophil-derived EVs also exhibit unique advantages as drug delivery vehicles. Aerosol administration enables efficient delivery of EVs to the lung tissues, offering a convenient route for drug administration in respiratory diseases. In terms of clinical translation, emerging studies have explored the clinical applications of EVs in COPD and lung cancer. Relevant research on COPD focuses on plasma exosomal miRNA biomarkers, while studies on lung cancer apply EV-based liquid biopsy to guide therapeutic strategies. Although these studies are not specifically designed to target senescence, they can all provide indirect evidence for the mechanisms underlying EV-mediated pulmonary senescence.
“EVs hold promise as tools for senotherapy, and the development of optimal EVs for senotherapies is becoming an important research focus,” notes Prof. Wang. At present, strategies such as drug loading, surface modification with targeting ligands, and aerosol delivery are being explored to optimize EV-based therapies for lung diseases. However, challenges remain, including standardization of isolation and characterization methods, large-scale clinical validation, and a deeper understanding of EV biology in the aging context. This comprehensive review provides a framework for future research and clinical translation. It is expected to pioneer a new paradigm for anti-senescence therapy for chronic respiratory diseases.
Reference
Title of original paper: Insights into extracellular vesicles in senescence-associated chronic lung diseases
Journal: Chinese Medical Journal
DOI: https://doi.org/10.1097/CM9.0000000000004208
About Professor Peter Barnes from Fellow of the Royal Society
MD, PhD, Fellow of the Royal College of Physicians, Fellow of the American College of Chest Physicians, Fellow of the Academy of Medical Sciences, Fellow of the Royal Society. He has published more than 1,500 peer-reviewed papers in the fields of asthma, chronic obstructive pulmonary disease and respiratory pharmacology, with an H-index of 230 and over 200,000 citations. He has authored or edited more than 50 monographs. Professor Barnes has long been engaged in research on the pathogenesis and therapeutic strategies of asthma and chronic obstructive pulmonary disease. His current primary research focus lies in the functional mechanisms of cellular senescence in chronic pulmonary diseases.
About Dr. Ruiying Wang
Chief Physician, MD, Master’s Supervisor, Deputy Director of the Department of Respiratory and Critical Care Medicine, Shanxi Bethune Hospital; Director of Shanxi Provincial COPD Diagnosis and Treatment Center; Visiting Scholar at Imperial College London. She has long been engaged in basic and clinical research on chronic obstructive pulmonary disease. She has presided over more than 10 projects funded by the National Natural Science Foundation of China and provincial-level research programs, and published over 20 academic papers including SCI-indexed articles.
Funding information
This work was supported by the Projects of International Cooperation and Exchanges NSFC (No. W2421096), and San Jin Talent Program Project of Shanxi Province (No. 210020157002).
Chinese Medical Journal
Literature review
Not applicable
Insights into extracellular vesicles in senescence-associated chronic lung diseases
13-Jul-2026
The authors declare no conflicts of interest