A comprehensive review finds that extracellular vesicles (EVs) propagate cellular senescence through a senescence-associated secretory phenotype (SASP), fueling inflammation and tissue dysfunction across diseases like COPD, idiopathic pulmonary fibrosis, asthma, bronchiectasis, obstructive sleep apnea, and lung cancer.

EVs connect infections, inflammation, vascular/cardiovascular issues, and tumor microenvironment remodeling to senescence signaling in bronchiectasis, obstructive sleep apnea, and lung cancer.

However, progress faces challenges such as inconsistent isolation and characterization methods, limited large-scale clinical validation, and a need to map how EV cargo shifts with age and disease severity.

Beyond pathology, EVs are being explored as therapeutic agents and delivery vehicles for senotherapy, with mesenchymal stem cell–derived EVs showing anti-inflammatory and anti-senescent effects in preclinical COPD and IPF models, and aerosol administration offering direct lung targeting.

Mechanistically, EVs deliver pathogenic microRNAs like miR-34a, miR-21, miR-125a-5p, miR-146a-5p, and miR-570-3p that suppress anti-aging molecules such as sirtuins, accelerating senescence and disease progression, exemplified in COPD (miR-34a/SIRT1) and IPF (miR-23b-3p/miR-494-3p targeting SIRT3), with asthma also showing links between miR-34a and aging pathways.

EVs are nanoscale cellular messengers carrying microRNAs, proteins, and lipids, central to aging-related chronic lung diseases.

The cargo of EVs reflects the state of the releasing cell, with senescent cells emitting pro-senescent payloads that trigger secondary senescence in neighboring cells, amplifying lung inflammation, damage, and fibrosis.

A unifying view suggests EV-mediated senescence signaling could bridge multiple chronic lung diseases, enabling cross-disease biomarkers and therapies and pointing toward anti-senescence treatments for respiratory conditions.