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Telomerase treatment prevents lung profibrotic pathologies associated with physiological aging

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Piñeiro-Hermida, Sergio and Autilio, Chiara and Martínez, Paula and Bosch, Fátima and Pérez-Gil, Jesús and Blasco, María A. (2020) Telomerase treatment prevents lung profibrotic pathologies associated with physiological aging. Journal of Cell Biology, 219 (10). pp. 1-21. ISSN 0021-9525; Electronic: 1540-8140

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Official URL: https://rupress.org/jcb/article/219/10/e202002120/152010/Telomerase-treatment-prevents-lung-profibrotic



Abstract

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.


Item Type:Article
Uncontrolled Keywords:Telomerase; Lung pathologies; Aging
Subjects:Medical sciences > Medicine > Pneumology
Medical sciences > Biology > Biochemistry
ID Code:64845
Deposited On:13 Apr 2021 10:55
Last Modified:14 Apr 2021 07:46

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