期刊
AUTOPHAGY
卷 17, 期 12, 页码 4341-4362出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/15548627.2021.1916194
关键词
Aging-related hearing loss; autophagy; FOXG1; hair cell; ROS
类别
资金
- National Basic Research Program of China [2017YFA0105201]
- Strategic Priority Research Program of the Chinese Academy of Science [XDA16010303]
- National Natural Science Foundation of China [81873700, 82030029, 81800915, 81230021, 81670929, 81400465, 81500795, 81970882]
- National Key R&D Program of China [2017YFA0103903]
- Natural Science Foundation from Jiangsu Province [BE2019711]
- Shenzhen Fundamental Research Program [JCYJ20190814093401920]
- Open Research Fund of the State Key Laboratory of Genetic Engineering, Fudan University [SKLGE1809]
Presbycusis, the result of aging on hearing, is closely related to common mitochondrial gene deletions. This study found that FOXG1 plays a crucial role in the degeneration process of the auditory system through regulation of autophagy. Aspirin was also found to increase FOXG1 expression and activate autophagy, suggesting a potential treatment for age-related hearing loss.
Presbycusis is the cumulative effect of aging on hearing. Recent studies have shown that common mitochondrial gene deletions are closely related to deafness caused by degenerative changes in the auditory system, and some of these nuclear factors are proposed to participate in the regulation of mitochondrial function. However, the detailed mechanisms involved in age-related degeneration of the auditory systems have not yet been fully elucidated. In this study, we found that FOXG1 plays an important role in the auditory degeneration process through regulation of macroautophagy/autophagy. Inhibition of FOXG1 decreased the autophagy activity and led to the accumulation of reactive oxygen species and subsequent apoptosis of cochlear hair cells. Recent clinical studies have found that aspirin plays important roles in the prevention and treatment of various diseases by regulating autophagy and mitochondria function. In this study, we found that aspirin increased the expression of FOXG1, which further activated autophagy and reduced the production of reactive oxygen species and inhibited apoptosis, and thus promoted the survival of mimetic aging HCs and HC-like OC-1 cells. This study demonstrates the regulatory function of the FOXG1 transcription factor through the autophagy pathway during hair cell degeneration in presbycusis, and it provides a new molecular approach for the treatment of age-related hearing loss.
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