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Its main characteristics are difficulties in understanding language and localizing sound. Presbycusis is an increasingly critical public health problem, but the underlying molecular mechanism has not been fully elucidated. Ferroptosis is a form of regulated cell death caused by iron\u2010 and reactive oxygen species\u2010induced lipid peroxidation. Ferroptosis is related to many pathological processes, but whether it participates in the degeneration of the auditory system remains unclear. To investigate this, we measured iron levels in a simulated ageing model established by the addition of <jats:sc>d<\/jats:sc>\u2010galactose (<jats:sc>d<\/jats:sc>\u2010gal). We found, for the first time, that iron accumulated within cells and that the ultrastructural features of ferroptosis appeared in the auditory cortex with ageing. These changes were accompanied by upregulation of iron regulatory protein 2 (IRP\u20102), which led to an increase in transferrin receptor 1 (TfR\u20101), thus increasing iron entry into cells and potentially leading to ferroptosis. In addition, the malondialdehyde (MDA) content and the occurrence of mitochondrial DNA common deletions (CDs) increased, neuron degeneration appeared, and glutathione (GSH) and superoxide dismutase (SOD) activity decreased. Furthermore, we found that treatment with the iron chelator deferoxamine (DFO) and knockdown of IRP\u20102 both relieved ferroptosis during the simulated ageing process, thus achieving a partial protective effect to delay ageing. In summary, we describe here the first discovery that age\u2010related iron deposition and ferroptosis may be associated with auditory cortex neurodegeneration. Relieving ferroptosis might thus be a new intervention strategy for age\u2010related hearing loss.<\/jats:p>","DOI":"10.1111\/febs.15266","type":"journal-article","created":{"date-parts":[[2020,2,29]],"date-time":"2020-02-29T05:55:35Z","timestamp":1582955735000},"page":"4747-4766","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":61,"title":["Relieving ferroptosis may partially reverse neurodegeneration of the auditory cortex"],"prefix":"10.1111","volume":"287","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0339-1743","authenticated-orcid":false,"given":"Xi","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology Union Hospital 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