Salahoru Constantin, Hînganu Marius Valeriu, Salahoru Paul, Hînganu Delia
Department of Morpho-Functional Sciences I, Faculty of Medicine, "Grigore T. Popa" University of Medicine and Pharmacy, 700115 Iasi, Romania.
Department of Surgery I, Faculty of Medicine, "Grigore T. Popa" University of Medicine and Pharmacy, 700115 Iasi, Romania.
Int J Mol Sci. 2025 May 27;26(11):5128. doi: 10.3390/ijms26115128.
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.
衰老影响生物体中的所有组织，包括气管支气管树，其结构和功能变化由氧化应激、细胞衰老、表观遗传修饰、线粒体功能障碍和端粒缩短等机制驱动。气道衰老可由内在或外在因素加速。本综述汇集了文献中关于气管支气管气道壁各层发生的分子变化的信息。它研究了与气道黏膜、黏膜下层、软骨和平滑肌衰老相关的生物分子变化。在黏膜水平，衰老会降低纤毛功能并破坏黏蛋白稳态，损害黏液纤毛清除功能，并导致慢性呼吸道疾病，如慢性阻塞性肺疾病（COPD）。细胞衰老和氧化应激驱动细胞外基质重塑和慢性炎症。气道软骨的胶原蛋白和纤连蛋白组成会发生与年龄相关的变化，导致硬度增加，而基质金属蛋白酶（MMP）活性增强会加剧细胞外基质（ECM）降解。在气道平滑肌中，衰老会引起钙信号传导、肥大以及促炎介质分泌的变化，进一步使气道重塑持续存在。这些变化会损害呼吸功能，并增加老年人对慢性呼吸道疾病的易感性。通过整合现有知识，本综述旨在全面概述呼吸道随衰老发生的分子变化，并突出该主题未来研究的新分子视角。
