Format

Send to

Choose Destination
Thorax. 2017 May;72(5):451-459. doi: 10.1136/thoraxjnl-2016-208964. Epub 2017 Jan 9.

Inhaled resveratrol treatments slow ageing-related degenerative changes in mouse lung.

Author information

1
Developmental Biology and Regenerative Medicine, Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, California, USA.
2
Craniofacial Biology Graduate Program, Herman Ostrow School of Dentistry of University of Southern California, Los Angeles, California, USA.

Abstract

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.

KEYWORDS:

Airway Epithelium; COPD Pathology; Histology/Cytology; Lung Physiology; Respiratory Measurement

PMID:
28070015
DOI:
10.1136/thoraxjnl-2016-208964
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center