RT Journal Article SR Electronic T1 The ageing lung under stress JF European Respiratory Review JO EUROPEAN RESPIRATORY REVIEW FD European Respiratory Society SP 200126 DO 10.1183/16000617.0126-2020 VO 29 IS 156 A1 Korfei, Martina A1 MacKenzie, BreAnne A1 Meiners, Silke YR 2020 UL http://err.ersjournals.com/content/29/156/200126.abstract AB Healthy ageing of the lung involves structural changes but also numerous cell-intrinsic and cell-extrinsic alterations. Among them are the age-related decline in central cellular quality control mechanisms such as redox and protein homeostasis. In this review, we would like to provide a conceptual framework of how impaired stress responses in the ageing lung, as exemplified by dysfunctional redox and protein homeostasis, may contribute to onset and progression of COPD and idiopathic pulmonary fibrosis (IPF). We propose that age-related imbalanced redox and protein homeostasis acts, amongst others (e.g. cellular senescence), as a “first hit” that challenges the adaptive stress-response pathways of the cell, increases the level of oxidative stress and renders the lung susceptible to subsequent injury and disease. In both COPD and IPF, additional environmental insults such as smoking, air pollution and/or infections then serve as “second hits” which contribute to persistently elevated oxidative stress that overwhelms the already weakened adaptive defence and repair pathways in the elderly towards non-adaptive, irremediable stress thereby promoting development and progression of respiratory diseases. COPD and IPF are thus distinct horns of the same devil, “lung ageing”.The ageing lung under stress https://bit.ly/2B3UOru