Mechanistic advances and emerging technologies redefining lung aging research

As the population ages, defining how biological processes change over the lifetime has become increasingly important. Acute and chronic lung diseases are more prevalent in older adults, and emerging research is beginning to uncover the mechanistic and cellular pathways that link aging to conditions such as pneumonia and chronic obstructive pulmonary disease (COPD). Additional mechanisms, particularly those involving extracellular vehicles (EVs), the microbiome, and sex differences, are now recognized as potential contributors to age-related changes in lung health, yet remain underexplored. Advances in experimental models and analytical tools have accelerated progress in the field. Three-dimensional lung models such as organoids, precision-cut lung slices, extracellular matrix (ECM) scaffolds, and lung-on-a-chip systems offer more physiologically relevant systems than traditional two-dimensional cultures, improving translatability to in vivo biology. Meanwhile, the expansion of genomics, transcriptomics, proteomics, and metabolomics has enabled comprehensive, multiomics approaches for mapping disease mechanisms, and such datasets are increasingly available. However, deeper integration with patient metadata and spatially resolved methods is still needed to advance precision medicine approaches to exploit aging mechanisms in chronic lung diseases. In this review, we highlight the importance of investigating EVs, the microbiome, and sex differences and their contribution of age-associated mechanisms in the context of pneumonia and COPD, and discuss how innovations in 3-D lung models and omics technologies are reshaping our understanding of the pathological mechanisms that underlie these diseases.