title: Inhaled resveratrol treatments slow ageing-related degenerative changes in mouse lung.
abstract: 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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  RSL prophylaxis by inhalation is a potential approach for slowing ageing-related deterioration of lung function and structure by maintaining AEC2 integrity.
authors.affiliation: Developmental Biology and Regenerative Medicine, Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, California, USA.|Craniofacial Biology Graduate Program, Herman Ostrow School of Dentistry of University of Southern California, Los Angeles, California, USA.
authors.forename: Sonia
authors.initials: S
authors.lastname: Navarro
authors.affiliation: Developmental Biology and Regenerative Medicine, Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, California, USA.
authors.forename: Raghava
authors.initials: R
authors.lastname: Reddy
authors.affiliation: Developmental Biology and Regenerative Medicine, Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, California, USA.
authors.forename: Jooeun
authors.initials: J
authors.lastname: Lee
authors.affiliation: Developmental Biology and Regenerative Medicine, Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, California, USA.
authors.forename: David
authors.initials: D
authors.lastname: Warburton
authors.affiliation: Developmental Biology and Regenerative Medicine, Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, California, USA.
authors.forename: Barbara
authors.initials: B
authors.lastname: Driscoll
mesh_terms: D000280:Administration, Inhalation; D000375:Aging / Q000187:drug effects*; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage* / Q000494:pharmacology*; D015153:Blotting, Western; D004249:DNA Damage / Q000187:drug effects; D020287:In Situ Nick-End Labeling; D008168:Lung / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D012129:Respiratory Function Tests; D000077185:Resveratrol; D013267:Stilbenes / Q000008:administration & dosage* / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D013267:Stilbenes; D000077185:Resveratrol
keywords: Airway Epithelium; COPD Pathology; Histology/Cytology; Lung Physiology; Respiratory Measurement