Donor age linked to abnormal cell changes in human lung organoids
Basal-cell colonies increased with donor age, reaching close to 100% in most donors by age 70 after 14 days in culture.
Limit: The DNA-accessibility comparison included only three donors with fibrosis and three age-matched controls
Edited by Boris Djordjevic · AgingResearch.News
Human alveolar type II cells, which help renew the lung’s air sacs, were studied in 14-day organoid experiments using non-diseased donors of both sexes. Researchers grew these three-dimensional cell structures with human lung fibroblasts, connective-tissue cells. With increasing donor age, a larger share of colonies developed basal cells, an airway cell type. A smaller share developed cells resembling the air sacs’ thin lining. Colonies counted as basal-cell colonies when at least 25% of their epithelial, or lining, cells carried a basal-cell marker.
Age-linked changes in chemical marks on DNA-packaging proteins suggested that the cells were poised to become basal cells. A shared set of genes was more accessible to gene-reading machinery in cells from donors with idiopathic pulmonary fibrosis, an age-associated lung-scarring disease. In lab experiments, an inflammatory signal reproduced this priming in young donor cells.
Why it matters
The authors propose a mechanism linking aging, inflammation and low oxygen to abnormal cell identities in fibrotic lung disease. It addresses how aging may alter the behavior of cells responsible for lung repair.
Caveats
The donor-age comparisons were observational, and the cell-conversion results came from organoids, not living lungs. The DNA-accessibility comparison included three donors with fibrosis and three age-matched controls; this preprint has not been peer-reviewed.
- Epigenetic regulation of gene expression
- Histone modification and chromatin remodeling
- Hypoxia and HIF signaling
- Idiopathic pulmonary fibrosis
- Bivalent chromatin marks
- Humans
The paper
University of California, San Francisco
bioRxiv, Jun 10, 2026, Open access, Preprint, not peer-reviewed
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