Telomerase treatment prevents lung profibrotic pathologies associated with physiological aging
Piñeiro-Hermida, Sergio (Centro Nacional de Investigaciones Oncológicas)
Autilio, Chiara (Universidad Complutense de Madrid. Departamento de Bioquímica y Biología Molecular)
Martínez, Paula (Centro Nacional de Investigaciones Oncológicas)
Bosch i Tubert, Fàtima (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Pérez-Gil, Jesús (Universidad Complutense de Madrid. Departamento de Bioquímica y Biología Molecular)
Blasco, María A. (Centro Nacional de Investigaciones Oncológicas)

Date:	2020
Abstract:	Here, we show that physiological aging in mice leads to degenerative and fibrotic-like pathologies in the lung and that telomerase gene therapy prevents the onset of these pathologies. Our findings highlight telomerase activation as a potential therapeutic strategy for lung degenerative pathologies associated with aging. Short/dysfunctional telomeres are at the origin of idiopathic pulmonary fibrosis (IPF) in patients mutant for telomere maintenance genes. However, it remains unknown whether physiological aging leads to short telomeres in the lung, thus leading to IPF with aging. Here, we find that physiological aging in wild-type mice leads to telomere shortening and a reduced proliferative potential of alveolar type II cells and club cells, increased cellular senescence and DNA damage, increased fibroblast activation and collagen deposits, and impaired lung biophysics, suggestive of a fibrosis-like pathology. Treatment of both wild-type and telomerase-deficient mice with telomerase gene therapy prevented the onset of lung profibrotic pathologies. These findings suggest that short telomeres associated with physiological aging are at the origin of IPF and that a potential treatment for IPF based on telomerase activation would be of interest not only for patients with telomerase mutations but also for sporadic cases of IPF associated with physiological aging.
Grants:	Ministerio de Economía y Competitividad SAF2013-45111-R Ministerio de Economía y Competitividad SAF2015-72455-EXP Ministerio de Ciencia e Innovación RTI2018-094564-B-100 Ministerio de Ciencia e Innovación DTS17/ 00152 Ministerio de Ciencia e Innovación SAF2017-82623-R
Note:	Altres ajuts: WCRF/16-1177, GCM/P2018/NMT-4389 i RyPSE-CM/B2017/BMD-3770
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Telòmer ; Pulmons ; Malalties
Published in:	The journal of cell biology, Vol. 219 (august 2020) , ISSN 1540-8140

DOI: 10.1083/jcb.202002120
PMID: 32777016

21 p, 7.3 MB

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Articles > Research articles
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