Alveolar epithelial regeneration in the aging lung

Abstract

Advancing age is the most important risk factor for the development of and mortality from acute and chronic lung diseases, including pneumonia, chronic obstructive pulmonary disease, and pulmonary fibrosis. This risk was manifest during the COVID-19 pandemic, when elderly people were disproportionately affected and died from SARS-CoV-2 pneumonia. However, the recent pandemic also provided lessons on lung resilience. An overwhelming majority of patients with SARS-CoV-2 pneumonia, even those with severe disease, recovered with near-complete restoration of lung architecture and function. These observations are inconsistent with historic views of the lung as a terminally differentiated organ incapable of regeneration. Here, we review emerging hypotheses that explain how the lung repairs itself after injury and why these mechanisms of lung repair fail in some individuals, particularly the elderly.

ECM and epithelial stem cells: the scaffold of destiny

“…Quantitative and qualitative changes through age have been documented for some lung progenitor populations. They display different behavior: Basal and club cells decrease in number with age, whereas AT2 cells number remain unchanged but harbor decreased functionality such as self-renewal and differentiation capacity ( Wansleeben et al, 2014 ; Ortega-Martínez et al, 2016 ; Han et al, 2023 ). Moreover, using alveolar organoids, it has been shown that isolated AT2 cells from old mice display a reduced capacity to form alveolar organoids when compared to young adult mice ( Rowbotham et al, 2023 ).…”