Hallmarks of the ageing lung – 10 years later

Aging is a crucial factor in the development of chronic lung diseases, including chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), and lung cancer. Marking the 10th anniversary of the original "Hallmarks of the aging lung" published in this Journal, we present an updated review highlighting key cellular and molecular features of aging that drive the onset and progression of these conditions. Aging stands as the most significant risk factor for chronic lung diseases, which are characterised by structural and functional changes such as reduced elasticity, persistent inflammation, and impaired repair capacity. Recent evidence confirms that nearly all recognised hallmarks of aging play a role in the pathogenesis of these diseases. Notably, extracellular matrix (ECM) dysregulation - first proposed as a lung aging hallmark in 2015 - has become an integral aspect of aging in lung disease. Environmental exposures, such as cigarette or wildfire smoke, accelerate age-related changes by increasing oxidative stress, promoting cellular senescence, and disrupting tissue homeostasis. In lung cancer, aging contributes to genomic alterations, epigenetic dysregulation, immune evasion, and therapeutic resistance. Additionally, the roles of extracellular vesicles and microbiome changes in shaping these aging phenotypes are emerging areas of research. Early clinical studies are now targeting specific aging hallmarks, such as cellular senescence, with the goal of reducing age-related pathology and improving outcomes. Overall, integrating aging biology into lung disease research paves the way for innovative diagnostic and therapeutic strategies that address common molecular mechanisms across multiple chronic lung conditions.