2026-07-21T08:13:15Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/182042024-11-30T00:35:59Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc Piñeiro-Hermida, Sergio author Martínez, Paula author Blasco, Maria A author Blasco, MA author 2021-05 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. Aging Cell . 2021;20(5):e13352. 10.1111/acel.13352 1474-9726 Aging cell 33942458 http://hdl.handle.net/20.500.12105/18204 Short and dysfunctional telomeres protect from allergen-induced airway inflammation.