2026-07-21T08:13:16Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/182042024-11-30T00:35:59Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
Piñeiro-Hermida, Sergio
author
Martínez, Paula
author
Blasco, Maria A
author
Blasco, MA
funder
Unión Europea. Comisión Europea. European Research Council (ERC)
funder
Instituto de Salud Carlos III
funder
Ministerio de Ciencia e Innovación (España)
funder
Fundación Banco Santander
2024-02-15T09:16:07Z
2024-02-15T09:16:07Z
2021-05
Aging Cell . 2021;20(5):e13352.
10.1111/acel.13352
1474-9726
Aging cell
33942458
http://hdl.handle.net/20.500.12105/18204
Asthma is a chronic inflammatory disease affecting 300 million people worldwide. As telomere shortening is a well-established hallmark of aging and that asthma incidence decreases with age, here we aimed to study the role of short telomeres in asthma pathobiology. To this end, wild-type and telomerase-deficient mice with short telomeres (third-generation (G3 Tert-/- mice)) were challenged with intranasal house dust mite (HDM) extract. We also challenged with HDM wild-type mice in which we induced a telomere dysfunction by the administration of 6-thio-2´-deoxyguanosine (6-thio-dG). Following HDM exposure, G3 Tert-/- and 6-thio-dG treated mice exhibited attenuated eosinophil counts and presence of hematopoietic stem cells in the bone marrow, as well as lower levels of IgE and circulating eosinophils. Accordingly, both G3 Tert-/- and 6-thio-dG treated wild-type mice displayed reduced airway hyperresponsiveness (AHR), as indicated by decreased airway remodeling and allergic airway inflammation markers in the lung. Furthermore, G3 Tert-/- and 6-thio-dG treated mice showed lower differentiation of Club cells, attenuating goblet cell hyperplasia. Club cells of G3 Tert-/- and 6-thio-dG treated mice displayed increased DNA damage and senescence and reduced proliferation. Thus, short/dysfunctional telomeres play a protective role in murine asthma by impeding both AHR and mucus secretion after HDM exposure. Therefore, our findings imply that telomeres play a relevant role in allergen-induced airway inflammation.
eng
Short and dysfunctional telomeres protect from allergen-induced airway inflammation.
journal article
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Shortanddysfunctionaltelomeresprotect_2021.pdf
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Shortanddysfunctionaltelomeresprotect_2021.pdf.txt