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Among them, lead is an extremely toxic heavy metal that poses serious health hazards to humans, particularly threatening vulnerable groups such as children and the elderly. Currently, the effects of chronic low\u2010dose lead exposure on the auditory system have yet to be reported. In this study, we established a chronic lead exposure mouse model and conducted comprehensive auditory function assessments. The results demonstrated that lead\u2010exposed mice developed high\u2010frequency hearing loss at early stages, which progressively worsened over time. Morphological examination of the inner ear revealed hair cell loss, reduced synaptic ribbon numbers, and disruption of gap junctions in lead\u2010exposed mice. Furthermore, immunofluorescence staining confirmed significantly decreased expression of the mitochondrial protease LONP1, along with markedly increased expression of its substrate HMGCS2, in the stria vascularis, sensory epithelium, and spiral ganglia of lead\u2010exposed mice. These findings indicate that chronic low\u2010level lead exposure causes inner ear damage and irreversible auditory dysfunction, while accelerating age\u2010related hearing loss in C57BL\/6J mice. These preclinical results suggest that chronic lead exposure may represent a significant risk factor for age\u2010related hearing loss, deepen our understanding of lead\u2010induced auditory system impairment, and hold profound implications for preventing hearing damage in populations at high risk of lead exposure.<\/jats:p>","DOI":"10.1111\/acel.70297","type":"journal-article","created":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T07:57:49Z","timestamp":1762847869000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Chronic Low\u2010Level Lead Exposure Causes Auditory Impairment and Accelerates the Progression of Age\u2010Related Hearing Loss in C57BL\/6J Mice"],"prefix":"10.1111","volume":"25","author":[{"given":"Xue","family":"Bai","sequence":"first","affiliation":[{"name":"Department of Otolaryngology, Head and Neck Surgery, The Second Affiliated Hospital of Nanchang University, Jiangxi Medical College Nanchang University  Nanchang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li\u2010Hua","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Jiangxi Medical College Nanchang University  Nanchang Jiangxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi\u2010Bin","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery, The Second Affiliated Hospital of Nanchang University, Jiangxi Medical College Nanchang University  Nanchang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai\u2010Lang","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Head and Neck Surgery, The Second Affiliated Hospital of Nanchang University, Jiangxi Medical College Nanchang University  Nanchang 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