{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T18:56:05Z","timestamp":1784141765094,"version":"3.55.0"},"reference-count":110,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T00:00:00Z","timestamp":1748304000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Aging affects all tissues in an organism, including the tracheobronchial tree, with structural and functional changes driven by mechanisms such as oxidative stress, cellular senescence, epigenetic modifications, mitochondrial dysfunction, and telomere shortening. Airway aging can be accelerated by intrinsic or extrinsic factors. This review brings together information from the literature on the molecular changes occurring in all layers of the tracheobronchial airway wall. It examines the biomolecular changes associated with aging in the mucosa, submucosa, cartilage, and smooth muscle of the airways. At the mucosal level, aging reduces ciliary function and disrupts mucin homeostasis, impairing mucociliary clearance and contributing to chronic respiratory diseases such as COPD (Chronic Obstructive Pulmonary Disease). Cellular senescence and oxidative stress drive extracellular matrix remodeling and chronic inflammation. Airway cartilage undergoes age-related changes in collagen and fibronectin composition, leading to increased stiffness, while heightened MMP (Matrix Metalloproteinases) activity exacerbates ECM (extracellular matrix) degradation. In airway smooth muscle, aging induces changes in calcium signaling, hypertrophy, and the secretion of pro-inflammatory mediators, further perpetuating airway remodeling. These changes impair respiratory function and increase susceptibility to chronic respiratory conditions in the elderly. By consolidating current knowledge, this review aims to provide a comprehensive overview of the molecular changes occurring in the respiratory tract with aging and to highlight new molecular perspectives for future research on this topic.<\/jats:p>","DOI":"10.3390\/ijms26115128","type":"journal-article","created":{"date-parts":[[2025,5,28]],"date-time":"2025-05-28T03:52:08Z","timestamp":1748404328000},"page":"5128","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Advances in Molecular Research of Tracheobronchial Tree Aging: A Systematic Review"],"prefix":"10.3390","volume":"26","author":[{"given":"Constantin","family":"Salahoru","sequence":"first","affiliation":[{"name":"Department of Morpho-Functional Sciences I, Faculty of Medicine, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marius Valeriu","family":"H\u00eenganu","sequence":"additional","affiliation":[{"name":"Department of Morpho-Functional Sciences I, Faculty of Medicine, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Salahoru","sequence":"additional","affiliation":[{"name":"Department of Surgery I, Faculty of Medicine, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9856-6496","authenticated-orcid":false,"given":"Delia","family":"H\u00eenganu","sequence":"additional","affiliation":[{"name":"Department of Morpho-Functional Sciences I, Faculty of Medicine, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1038\/s41392-022-01211-8","article-title":"Epigenetic Regulation of Aging: Implications for Interventions of Aging and Diseases","volume":"7","author":"Wang","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Salameh, Y., Bejaoui, Y., and El Hajj, N. (2020). DNA Methylation Biomarkers in Aging and Age-Related Diseases. Front. Genet., 11.","DOI":"10.3389\/fgene.2020.00171"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Horvath, S. (2013). DNA Methylation Age of Human Tissues and Cell Types. 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