TY - JOUR AU - Houssaini, Amal AU - Breau, Marielle AU - Kebe, Kanny AU - Abid, Shariq AU - Marcos, Elisabeth AU - Lipskaia, Larissa AU - Rideau, Dominique AU - Parpaleix, Aurelien AU - Huang, Jin AU - Amsellem, Valerie AU - Vienney, Nora AU - Validire, Pierre AU - Maitre, Bernard AU - Attwe, Aya AU - Lukas, Christina AU - Vindrieux, David AU - Boczkowski, Jorge AU - Derumeaux, Genevieve AU - Pende, Mario AU - Bernard, David AU - Meiners, Silke AU - Adnot, Serge T1 - mTOR pathway activation drives lung cell senescence and emphysema PY - 2018/02/08/ AB - 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. JF - JCI Insight JA - JCI Insight SN - 2379-3708 DO - 10.1172/jci.insight.93203 VL - 3 IS - 3 UR - https://doi.org/10.1172/jci.insight.93203 PB - The American Society for Clinical Investigation ER -