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Updated: Mar 9, 2026
Lung Fixation under Constant Pressure for Evaluation of Emphysema in Mice
Published on: September 26, 2019
Inhaled resveratrol treatments slow ageing-related degenerative changes in mouse lung
Sonia Navarro1,2, Raghava Reddy1, Jooeun Lee1
1Developmental Biology and Regenerative Medicine, Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, California, USA.
Background:
Lung ageing, a significant risk factor for chronic human lung diseases such as COPD and emphysema, is characterised by airspace enlargement and decreasing lung function. Likewise, in prematurely ageing telomerase null (terc-/-) mice, p53 stabilisation within diminishing numbers of alveolar epithelial type 2 cells (AEC2) accompanies reduced lung function. Resveratrol (RSL) is a plant phytoalexin that has previously showed efficacy in enhancing invertebrate longevity and supporting mammalian muscle metabolism when delivered orally. Here, we tested whether inhaled RSL could protect young, terc-/- mice from accelerated ageing of the lung.
Methods:
terc-/- mice aged 2 months inhaled 1 mg/kg RSL that was instilled intratracheally once per month for 3 months. One month after the last inhalation, whole lung function, structure and cellular DNA damage were evaluated and AEC2 survival was assessed by western blotting for survival pathway gene expression.
Results:
RSL treatments delayed the loss of lung compliance (p<0.05), maintained lung structure (p<0.001) and blocked parenchymal cell DNA damage as measured by TdT Nick-End Labeling (TUNEL). RSL, a known agonist of deacetylase SIRT1, supported AEC2 survival by stimulating SIRT1 expression, promoting p53 destabilisation and decreasing Bax expression and by maintaining expression levels of Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), activated p-Akt and p-Mdm2 and inactivated Phospho-Phosphatase and tensin homolog (p-PTEN).
Conclusions:
RSL prophylaxis by inhalation is a potential approach for slowing ageing-related deterioration of lung function and structure by maintaining AEC2 integrity.
