机构：[1]Department of Biomedical Sciences, Creighton University School of Medicine, Omaha, NE 68178, USA[2]Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University/University of Georgia Medical Partnership, Athens, GA, USA[3]Chongqing Academy of Animal Sciences, Chongqing 402460, China[4]Department of Otorhinolaryngology-Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China临床科室耳鼻咽喉-头颈外科首都医科大学附属北京同仁医院首都医科大学附属同仁医院
Age-related hearing loss (ARHL) negatively impacts quality of life in the elderly population. The prevalent cause of ARHL is loss of mechanosensitive cochlear hair cells (HCs). The molecular and cellular mechanisms of HC degeneration remain poorly understood. Using RNA-seq transcriptomic analyses of inner and outer HCs isolated from young and aged mice, we show that HC aging is associated with changes in key molecular processes, including transcription, DNA damage, autophagy, and oxidative stress, as well as genes related to HC specialization. At the cellular level, HC aging is characterized by loss of stereocilia, shrinkage of HC soma, and reduction in outer HC mechanical properties, suggesting that functional decline in mechanotransduction and cochlear amplification precedes HC loss and contributes to ARHL. Our study reveals molecular and cytological profiles of aging HCs and identifies genes such as Sod1, Sirt6, Jund, and Cbx3 as biomarkers and potential therapeutic targets for ameliorating ARHL.
基金：
This work has been supported by the NIH grant R01 DC016807 from the
NIDCD to D.H. Y.L. is supported by National Science Foundation of China
(#81870718). L.C. is supported by National Science Foundation of China
(#31771376). We acknowledge the use of the Auditory and Vestibular Technology
(AVT) Core of Translational Hearing Research Center at Creighton University
for imaging and the University of Nebraska DNA Sequencing Core Facility
for RNA-seq and Advanced Microscopy Core Facility for scanning electron microscopy.
The AVT core at Creighton receives partial support from NIH grant
1P20GM139762-01 from the NIGMS. The University of Nebraska DNA
Sequencing Core receives partial support from the NIH’s NCRR (RR018788).
Scanning electron microscope was acquired through a Nebraska EPSCoR
MRI award to Dr. Joel Destino (Creighton-Department of Chemistry &
Biochemistry) and was wholly funded by Nebraska EPSCoR.
第一作者机构：[1]Department of Biomedical Sciences, Creighton University School of Medicine, Omaha, NE 68178, USA
通讯作者：
通讯机构：[1]Department of Biomedical Sciences, Creighton University School of Medicine, Omaha, NE 68178, USA[2]Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University/University of Georgia Medical Partnership, Athens, GA, USA[4]Department of Otorhinolaryngology-Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China
推荐引用方式(GB/T 7714)：
Liu Huizhan,Giffen Kimberlee P.,Chen Lei,et al.Molecular and cytological profiling of biological aging of mouse cochlear inner and outer hair cells[J].CELL REPORTS.2022,39(2):doi:10.1016/j.celrep.2022.110665.
APA：
Liu, Huizhan,Giffen, Kimberlee P.,Chen, Lei,Henderson, Heidi J.,Cao, Talia A....&He, David Z..(2022).Molecular and cytological profiling of biological aging of mouse cochlear inner and outer hair cells.CELL REPORTS,39,(2)
MLA：
Liu, Huizhan,et al."Molecular and cytological profiling of biological aging of mouse cochlear inner and outer hair cells".CELL REPORTS 39..2(2022)
生物学