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Neurobiol Aging. 2015 Apr;36(4):1692-1701. doi: 10.1016/j.neurobiolaging.2014.12.034. Epub 2015 Jan 6.

Activation of miR-34a/SIRT1/p53 signaling contributes to cochlear hair cell apoptosis: implications for age-related hearing loss.

Author information

1
Department of Otolaryngology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China; Institute of Hearing and Speech-Language Science, Sun Yat-sen University, Guangzhou, China.
2
Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
3
Guangzhou Occupational Disease Prevention and Treatment Center, Guangzhou, China.
4
Department of Otolaryngology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China; Institute of Hearing and Speech-Language Science, Sun Yat-sen University, Guangzhou, China. Electronic address: yiqingzheng@hotmail.com.

Abstract

The molecular mechanisms underlying age-related hearing loss are not fully understood, and currently, there is no treatment for this disorder. MicroRNAs have recently been reported to be increasingly associated with age-related diseases and are emerging as promising therapeutic targets. In this study, miR-34a/Sirtuin 1 (SIRT1)/p53 signaling was examined in cochlear hair cells during aging. MiR-34a, p53 acetylation, and apoptosis increased in the cochlea of C57BL/6 mice with aging, whereas an age-related decrease in SIRT1 was observed. In the inner ear HEI-OC1 cell line, miR-34a overexpression inhibited SIRT1, leading to an increase in p53 acetylation and apoptosis. Moreover, miR-34a knockdown increased SIRT1 expression and diminished p53 acetylation, and apoptosis. Additionally, resveratrol, an activator of SIRT1, significantly rescued miR-34a overexpression-induced HEI-OC1 cell death and significantly reduced hearing threshold shifts and hair cell loss in C57BL/6 mice after a 2-month administration. Our results support a link between age-related cochlear hair cell apoptosis and miR-34a/SIRT1/p53 signaling, which may serve as a potential target for age-related hearing loss treatment.

KEYWORDS:

Cochlea; MicroRNA; Presbycusis; SIRT1; p53

[Indexed for MEDLINE]

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