Telomerase treatment prevents lung profibrotic pathologies associated with physiological aging.
Journal
The Journal of cell biology
ISSN: 1540-8140
Titre abrégé: J Cell Biol
Pays: United States
ID NLM: 0375356
Informations de publication
Date de publication:
05 10 2020
05 10 2020
Historique:
received:
21
02
2020
revised:
23
06
2020
accepted:
17
07
2020
entrez:
11
8
2020
pubmed:
11
8
2020
medline:
25
3
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32777016
pii: 152010
doi: 10.1083/jcb.202002120
pmc: PMC7659728
pii:
doi:
Substances chimiques
Bleomycin
11056-06-7
Telomerase
EC 2.7.7.49
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2020 Piñeiro-Hermida et al.
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