%0 Journal Article %A Martina Korfei %A David Klaus %A Daniel Stelmaszek %A Clemens Ruppert %A Ingrid Henneke %A Werner Seeger %A Andreas Guenther %T Lung ageing in C57/Bl6 and BALB/c mice is characterized by a defective surfactant metabolism, increased ER stress and inflammasome induction %D 2016 %R 10.1183/13993003.congress-2016.PA954 %J European Respiratory Journal %P PA954 %V 48 %N suppl 60 %X Introduction: Accelerated lung ageing is observed in both IPF and COPD. We performed phenotyping of lungs from aged C57/Bl6- (24 mo, n=15) and BALB/c mice (18 mo, n=12) in comparison to young animals of both strains (6 we, n=12) in order to elucidate the mechanisms of lung ageing.Methods: Murine lung tissue was analyzed by RT-PCR, immunoblotting and IHC.Results: H&E stainings of lung sections revealed that only 35% of aged mice indicated signs of slight emphysema. However, the number of alveolar type-II cells were markedly reduced in aged compared to young mice. As expected, enzymes involved in telomere-maintenance [Tert, Pot1, sirtuin1] were reduced in lungs of aged mice. Furthermore, protein synthesis of Abca3 and surfactant proteins (SP)-B/C was significantly reduced in lung tissue of aged mice, and was associated with a marked lack of mature forms of SP-B/C in BALF. Despite reduced surfactant protein synthesis, accumulation of unprocessed SP-B precursors was detectable in BALF and lung tissue of aged, but not young mice. In line with this, SP-processing proteases and the ER folding-chaperone calnexin were downregulated in lungs of aged mice. In addition, markers for ER stress [Xbp1, Chop] and inflammasome [Nlrp3, caspases-1/-11] were elevated in aged lungs, whereas components of the ERAD machinery and proteasome [Vcp, Psme1, Rpn6] were reduced in lungs of aged mice. IHC analyses showed that all these changes were localized to alveolar epithelium. The same phenotype was observed in aged BALB/c mice, which became no older than 18 months.Discussion: We postulate that the lung ageing-process is generating a vulnerable alveolar epithelium. %U