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Houssaini, A. ; Breau, M.* ; Kebe, K.* ; Abid, S.* ; Marcos, E.* ; Lipskaia, L.* ; Rideau, D.* ; Parpaleix, A.* ; Huang, J.* ; Amsellem, V.* ; Vienney, N.* ; Validire, P.* ; Maitre, B.* ; Attwe, A.* ; Lukas, C. ; Vindrieux, D.* ; Boczkowski, J.* ; Derumeaux, G.* ; Pende, M.* ; Bernard, D.* ; Meiners, S. ; Adnot, S.*

mTOR pathway activation drives lung cell senescence and emphysema.

JCI insight 3:93203 (2018)
Publ. Version/Full Text DOI PMC
Open Access Gold
Chronic obstructive pulmonary disease (COPD) is a highly prevalent and devastating condition for which no curative treatment is available. Exaggerated lung cell senescence may be a major pathogenic factor. Here, we investigated the potential role for mTOR signaling in lung cell senescence and alterations in COPD using lung tissue and derived cultured cells from patients with COPD and from age- and sex-matched control smokers. Cell senescence in COPD was linked to mTOR activation, and mTOR inhibition by low-dose rapamycin prevented cell senescence and inhibited the proinflammatory senescence-associated secretory phenotype. To explore whether mTOR activation was a causal pathogenic factor, we developed transgenic mice exhibiting mTOR overactivity in lung vascular cells or alveolar epithelial cells. In this model, mTOR activation was sufficient to induce lung cell senescence and to mimic COPD lung alterations, with the rapid development of lung emphysema, pulmonary hypertension, and inflammation. These findings support a causal relationship between mTOR activation, lung cell senescence, and lung alterations in COPD, thereby identifying the mTOR pathway as a potentially new therapeutic target in COPD.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Aging ; Copd ; Cellular Senescence ; Pulmonology
ISSN (print) / ISBN 2379-3708
e-ISSN 2379-3708
Journal JCI insight
Quellenangaben Volume: 3, Issue: 3, Pages: , Article Number: 93203 Supplement: ,
Publisher Clarivate
Publishing Place Ann Arbor, Michigan
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Lung Health and Immunity (LHI)