1. Telomerase Prevents Emphysema in Old Mice by Sustaining Subpopulations of Endothelial and AT2 Cells
- Author
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Marielle Breau, Christelle Cayrou, Dmitri Churikov, Charles Fouillade, Sandra Curras-Alonso, Serge Bauwens, Frederic Jourquin, Laura Braud, Frederic Fiore, Rémy Castellano, Emmanuelle Josselin, Carlota Sánchez-Ferrer, Giovanna Giovinazzo, Eric Gilson, Ignacio Flores, Arturo Londono-Vallejo, Serge Adnot, Vincent Géli, Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Curie [Paris], Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Centre d'Immunophénomique (CIPHE), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de neurosciences intégratives et cognitives (CNIC), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-Centre National de la Recherche Scientifique (CNRS), Université Côte d'Azur (UCA), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Université Nice Sophia Antipolis (... - 2019) (UNS), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-Centre National de la Recherche Scientifique (CNRS), and CAYROU, CHRISTELLE
- Subjects
0303 health sciences ,telomere ,[SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM] ,senescence ,aging ,[SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC] ,respiratory system ,[SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM] ,lung ,stem cell ,03 medical and health sciences ,0302 clinical medicine ,emphysema ,[SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC] ,Telomerase ,030217 neurology & neurosurgery ,030304 developmental biology - Abstract
Accumulation of senescent cells has been causally linked to the development of age-related pathologies. Here, we characterized a new mouse model (p21+/Tert) whose telomerase (TERT) is expressed from the p21 promoter that can be activated in response to telomere dysfunction. Lung parenchyma from p21+/Tert old mice accumulated fewer senescent cells with age and this correlated with a reduction in age-related alveolar space enlargement, a feature of pulmonary emphysema. This protection against emphysema depends on TERT catalytic activity and is associated with increased proliferation of pulmonary endothelial cells (EC) and capillary density. Single-cell RNA sequencing of lung cells revealed that TERT expression was associated with the enrichment of ECs expressing genes involved in vessel regeneration and in AT2 cells overexpressing S/G2M markers. These findings indicate that p21-promoter-dependent expression of catalytically active telomerase prevents emphysema by sustaining the proliferation of subclasses of EC and AT2 cells.
- Published
- 2022