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However, the cochlear aging process does not affect people uniformly, suggesting that both genetic and environmental (e.g., noise, ototoxic drugs) factors and their interaction may influence the onset and severity of ARHL. Considering the potential links between thyroid hormone, mitochondrial activity, and hearing, here, we probed the role of p43, a N-terminally truncated and ligand-binding form of the nuclear receptor TR\u03b11, in hearing function and in the maintenance of hearing during aging in p43<jats:sup>\u2212\/\u2212<\/jats:sup>mice through complementary approaches, including in vivo electrophysiological recording, ultrastructural assessments, biochemistry, and molecular biology.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found that the p43<jats:sup>\u2212\/\u2212<\/jats:sup>mice exhibit no obvious hearing loss in juvenile stages, but that these mice developed a premature, and more severe, ARHL resulting from the loss of cochlear sensory outer and inner hair cells and degeneration of spiral ganglion neurons. Exacerbated ARHL in p43<jats:sup>\u2212\/\u2212<\/jats:sup>mice was associated with the early occurrence of a drastic fall of SIRT1 expression, together with an imbalance between pro-apoptotic Bax, p53 expression, and anti-apoptotic Bcl2 expression, as well as an increase in mitochondrial dysfunction, oxidative stress, and inflammatory process. Finally, p43<jats:sup>\u2212\/\u2212<\/jats:sup>mice were also more vulnerable to noise-induced hearing loss.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These results demonstrate for the first time a requirement for p43 in the maintenance of hearing during aging and highlight the need to probe the potential link between human<jats:italic>THRA<\/jats:italic>gene polymorphisms and\/or mutations and accelerated age-related deafness or some adult-onset syndromic deafness.<\/jats:p><\/jats:sec>","DOI":"10.1186\/s12915-021-00953-1","type":"journal-article","created":{"date-parts":[[2021,2,1]],"date-time":"2021-02-01T18:03:50Z","timestamp":1612202630000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Exacerbated age-related hearing loss in mice lacking the p43 mitochondrial T3 receptor"],"prefix":"10.1186","volume":"19","author":[{"given":"Corentin","family":"Affortit","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7ois","family":"Casas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Ladrech","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Charles","family":"Ceccato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e9r\u00f4me","family":"Bourien","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolanne","family":"Coyat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Luc","family":"Puel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Lenoir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2670-719X","authenticated-orcid":false,"given":"Jing","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,2,1]]},"reference":[{"key":"953_CR1","doi-asserted-by":"publisher","first-page":"138","DOI":"10.3389\/fnagi.2015.00138","volume":"7","author":"M Magarinos","year":"2015","unstructured":"Magarinos M, Milo M, Varela-Nieto I. 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