Alveolar epithelial regeneration in the aging lung

• Published in: The Journal of clinical investigation Vol. 133; no. 20
• Main Authors: Han, SeungHye, Budinger, G R Scott, Gottardi, Cara J
• Format: Journal Article
• Language: English
• Published: United States American Society for Clinical Investigation 16-10-2023
• Subjects: Age factors in disease; Aged; Aging; Analysis; Bacterial pneumonia; Care and treatment; COVID-19 - pathology; Diagnosis; Disease susceptibility; Drugs; Health aspects; Humans; Lung - pathology; Lung diseases, Obstructive; Pandemics; Pneumonia; Pneumonia - pathology; Pulmonary Fibrosis - pathology; Regeneration; Review Series; RNA sequencing; SARS-CoV-2; United States
• ISSN: 1558-8238; 0021-9738; 1558-8238
• DOI: 10.1172/JCI170504

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.