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As SASP markers, we measured the mRNA levels of Il1a, Il6, Ifna and Ifnb. Furthermore, we explored whether an alteration of alternative splicing is associated with senescence by measuring the Adipor2 cryptic exon inclusion levels, a specific splicing variant repressed by TAR DNA-binding protein (TDP-43; encoded by Tardbp). Transgenic mice showed an atypical senescence profile with high p16 and p21 mRNA and protein in glia, without the canonical increase in SA-\u03b2-gal activity. Consistent with SASP, there was an increase in Il1a and Il6 expression, associated with increased TNF-R and M-CSF protein levels, with females being partially protected. TDP-43 splicing activity was compromised in this model, and the senolytic drug Navitoclax did not alter the disease progression. This lack of effect was reproduced in vitro, in contrast to dasatinib and quercetin, which diminished p16 and p21. Our findings show a non-canonical profile of senescence biomarkers in the model hSOD1-G93A.<\/jats:p>","DOI":"10.1242\/dmm.049059","type":"journal-article","created":{"date-parts":[[2022,8,2]],"date-time":"2022-08-02T08:16:32Z","timestamp":1659428192000},"source":"Crossref","is-referenced-by-count":25,"title":["A motor neuron disease mouse model reveals a non-canonical profile of senescence biomarkers"],"prefix":"10.1242","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7903-3478","authenticated-orcid":false,"given":"Pascual","family":"Torres","sequence":"first","affiliation":[{"name":"Metabolic Pathophysiology Research Group 1 , Department of Experimental Medicine , Lleida , Spain"},{"name":"University of Lleida-IRBLleida, 25196 1 , Department of Experimental Medicine , Lleida , 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Lleida-IRBLleida, 25196 1 , Department of Experimental Medicine , Lleida , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3509-7431","authenticated-orcid":false,"given":"Mario","family":"Encinas","sequence":"additional","affiliation":[{"name":"University of Lleida-IRBLleida, 25196 2 Oncogenic Signalling and Development, Department of Experimental Medicine , Lleida , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7991-669X","authenticated-orcid":false,"given":"M\u00f2nica","family":"Povedano","sequence":"additional","affiliation":[{"name":"Functional Unit of Amyotrophic Lateral Sclerosis (UFELA), Service of Neurology, Bellvitge University Hospital, 08907 Hospitalet de Llobregat, Barcelona 3 , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pol","family":"Andr\u00e9s-Benito","sequence":"additional","affiliation":[{"name":"University of Barcelona, 08907 Hospitalet de Llobregat, Barcelona 4 Department of Pathology and Experimental Therapeutics , , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9888-8754","authenticated-orcid":false,"given":"Isidre","family":"Ferrer","sequence":"additional","affiliation":[{"name":"University of Barcelona, 08907 Hospitalet de Llobregat, Barcelona 4 Department of Pathology and Experimental Therapeutics , , Spain"},{"name":"Biomedical Network Research Center on Neurodegenerative Diseases (CIBERNED) 5 , , , Spain"},{"name":"Institute Carlos III 5 , , , Spain"},{"name":"08907 Hospitalet de Llobregat, Barcelona 5 , , , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1496-966X","authenticated-orcid":false,"given":"Vict\u00f2ria","family":"Ayala","sequence":"additional","affiliation":[{"name":"Metabolic Pathophysiology Research Group 1 , Department of Experimental Medicine , Lleida , 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