Ageing exacerbates lung inflammation and fibrosis: lessons from the mouse models.

Pulmonary fibrosis is predominantly a disease of older adults. However, the processes underlying aging which might significantly influence the development of the fibrotic lung disease remain unidentified. In this study, we explored the lung responses of young (3 months) and old (18 months) mice to saline or bleomycin, an inducer of lung fibrosis. At baseline, elderly mice displayed pulmonary inflammation associated with T and B lymphocyte accumulation and increased cytokine expression. Aging was also related with basal alteration of extracellular matrix and marked deposition of collagen. The lungs of old mice exhibited worse fibrosis after bleomycin compared with the lungs from young mice as estimated by histological and biochemical analyses. To study the molecular mechanisms underlying the exaggerated inflammation and fibrosis in elderly mice, we used a microarray approach to characterize the pulmonary transcriptome of old and young animals. The aged lung alterations were correlated with senescent cell accumulation as shown by an increase of p16CDKN2A and pRb expression and an accumulation of β galactosidase-positive cells in elderly mice. Interestingly, the number of p16-positive lung epithelial cells and the expression of CDNK2 mRNA were correlated with fibrosis score in patients. We thus concluded that the senescence-related alterations in the lungs might be responsible of the higher susceptibility to lung inflammation and fibrosis in elderly animals and individuals.