PMID- 29344647 OWN - NLM STAT- MEDLINE DCOM- 20180829 LR - 20230106 IS - 1791-244X (Electronic) IS - 1107-3756 (Print) IS - 1107-3756 (Linking) VI - 41 IP - 4 DP - 2018 Apr TI - Autophagy regulates the degeneration of the auditory cortex through the AMPK-mTOR-ULK1 signaling pathway. PG - 2086-2098 LID - 10.3892/ijmm.2018.3393 [doi] AB - Presbycusis is the most common sensory impairment associated with aging; however, the underlying molecular mechanism remains unclear. Autophagy has been demonstrated to serve a key role in diverse diseases; however, no studies have examined its function in central presbycusis. The aim of the present study was to investigate the changes of autophagy in the physiological processes of the auditory cortex and its role in the degeneration of the auditory cortex, as well as the related mechanisms using naturally aging rats and a D‑galactose (D‑gal)‑induced mimetic rat model of aging. The present study demonstrated that autophagy increased from 3 months to 15 months in the normal saline (NS) control group, while it decreased in the D‑gal group. Compared with the age‑matched NS group, the D‑gal group demonstrated significantly increased levels of the autophagy‑related proteins, LC3 and Beclin 1 (BECN1) and the anti‑apoptotic proteins B‑cell lymphoma (BCL)2 and BCL‑extra large (BCL‑xL) at 3 months, with no obvious changes in cell apoptosis level and neuron ultrastructural morphology. However, LC3, BECN1, BCL2 and BCL‑xL were decreased at 15 months in the D-gal group, with cell apoptosis significantly increased and substantial neuron degeneration. Additionally, 5' AMP‑activated protein kinase (AMPK) activity was enhanced, and mechanistic target of rapamycin (mTOR) and ULK1 phosphorylation (Ser 757) activities were inhibited at 3 months compared with those of the NS group, while the opposite was observed at 9 and 15 months. The present results suggested that autophagy increases from young to adult and decreases at old age in the physiological processes of the auditory cortex, and has anti‑apoptotic as well as anti‑aging functions in the degeneration of the auditory cortex. Additionally, autophagy was regulated through AMPK activation and mTOR suppression, and impairment of autophagy may serve a key role in the degeneration of the auditory cortex, even in the pathogenesis of central presbycusis. FAU - Yuan, Jie AU - Yuan J AD - Department of Otolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China. FAU - Zhao, Xueyan AU - Zhao X AD - Department of Otolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China. FAU - Hu, Yujuan AU - Hu Y AD - Department of Otolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China. FAU - Sun, Haiying AU - Sun H AD - Department of Otolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China. FAU - Gong, Guoqing AU - Gong G AD - Department of Otolaryngology, Central Hospital of Huangshi, Huangshi, Hubei 435000, P.R. China. FAU - Huang, Xiang AU - Huang X AD - Institute of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China. FAU - Chen, Xubo AU - Chen X AD - Department of Otolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China. FAU - Xia, Mingyu AU - Xia M AD - Department of Otolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China. FAU - Sun, Chen AU - Sun C AD - Department of Otolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China. FAU - Huang, Qilin AU - Huang Q AD - Department of Otolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China. FAU - Sun, Yu AU - Sun Y AD - Department of Otolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China. FAU - Kong, Wen AU - Kong W AD - Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China. FAU - Kong, Weijia AU - Kong W AD - Department of Otolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China. LA - eng PT - Journal Article DEP - 20180117 PL - Greece TA - Int J Mol Med JT - International journal of molecular medicine JID - 9810955 RN - EC 2.7.1.1 (mTOR protein, rat) RN - EC 2.7.11.1 (Autophagy-Related Protein-1 Homolog) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - EC 2.7.11.1 (ULK1 protein, rat) RN - EC 2.7.11.31 (AMP-Activated Protein Kinases) SB - IM MH - AMP-Activated Protein Kinases/*metabolism MH - *Aging MH - Animals MH - Apoptosis MH - Auditory Cortex/cytology/*physiology MH - *Autophagy MH - Autophagy-Related Protein-1 Homolog/metabolism MH - Male MH - Rats, Sprague-Dawley MH - *Signal Transduction MH - TOR Serine-Threonine Kinases/metabolism PMC - PMC5810242 COIS- Competing interests The authors declare that they have no competing interests. EDAT- 2018/01/19 06:00 MHDA- 2018/08/30 06:00 PMCR- 2018/01/17 CRDT- 2018/01/19 06:00 PHST- 2017/02/01 00:00 [received] PHST- 2018/01/10 00:00 [accepted] PHST- 2018/01/19 06:00 [pubmed] PHST- 2018/08/30 06:00 [medline] PHST- 2018/01/19 06:00 [entrez] PHST- 2018/01/17 00:00 [pmc-release] AID - ijmm-41-04-2086 [pii] AID - 10.3892/ijmm.2018.3393 [doi] PST - ppublish SO - Int J Mol Med. 2018 Apr;41(4):2086-2098. doi: 10.3892/ijmm.2018.3393. Epub 2018 Jan 17.