Fig. TSC-mTORC1 signaling pathway affects the occurrence of deafness in the cochlea by regulating redox

 Supported by the grant from National Natural Science Foundation of China (No. 81670943) and other funding, a team led by Prof. Jiangang Gao at School of Life Science and Key Laboratory of the Ministry of Education for Experimental Teratology, Shandong University, and Prof. Haibo Wang at Department of Otolaryngology–Head and Neck Surgery, Provincial Hospital Affiliated to Shandong University, made significant advances in understanding the mechanism of age related hearing loss. In November 2018, their paper entitled “Tuberous sclerosis complex–mediated mTORC1 overactivation promotes age-related hearing loss” was published in the Journal of Clinical Investigation. The co-correspondence authors are Prof. Jiangang Gao and Haibo Wang. The first author is Dr. Xiaolong Fu. The link of this paper is https://www.jci.org/articles/view/98058.

          Age-related hearing loss (ARHL) is the most common chronic sensory disorder in the elderly. The high incidence of ARHL has become a common social and health problem. In order to reveal the specific pathogenesis of ARHL, they found that the activity of mammalian target of rapamycin complex 1 (mTORC1) in cochlear sensory neurons (NSE) was significantly increased in elderly C57BL/6J mice. They further developed raptor-specific knockout mice (inactivation of mTORC1 signaling pathway) and Tsc1 knockout mice (persistent activation of mTORC1 signaling pathway) in NSE. The inactivation of mTORC1 signaling pathway in cochlear NSE was sufficient to prevent ARHL in mice. Conversely, the persistent activation of mTORC1 signaling pathway in NSE could lead to premature death of hair cells. Further studies showed that rapamycin and antioxidant NAC could prevent the damage of auditory hair cells in Tsc1-/- mice. In addition, peroxisome was found to be an important signaling organelle involved in the regulation of mTORC1 signal in inner hair cells. This is the first study to elucidate the role of mTORC1 signaling pathway in ARHL, thus providing new insight for the prevention and treatment of ARHL.