Molecular and cytological profiling of biological aging of mouse cochlear inner and outer hair cells

Huizhan Liu; Kimberlee P. Giffen; Lei Chen; Heidi J. Henderson; Talia A. Cao; Grant A. Kozeny; Kirk Beisel; Yi Li; David Z. He

doi:10.1016/j.celrep.2022.110665

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Molecular and cytological profiling of biological aging of mouse cochlear inner and outer hair cells

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Molecular and cytological profiling of biological aging of mouse cochlear inner and outer hair cells

Huizhan Liu, Kimberlee P. Giffen, Lei Chen, Heidi J. Henderson, Talia A. Cao, Grant A. Kozeny, Kirk Beisel, Yi Li and David Z. He

Cell Reports, Vol.39(2), 110665

04/12/2022

DOI: https://doi.org/10.1016/j.celrep.2022.110665

PMID: 35417713

Abstract

Biochemistry, Genetics and Molecular Biology(all)

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.

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Title: Molecular and cytological profiling of biological aging of mouse cochlear inner and outer hair cells
Creators: Huizhan Liu (Author) - Creighton University
Kimberlee P. Giffen (Author) - Creighton University;Augusta University/University of Georgia Medical Partnership
Lei Chen (Author) - Creighton University;Chongqing Academy of Animal Science
Heidi J. Henderson (Author) - Creighton University
Talia A. Cao (Author) - Creighton University
Grant A. Kozeny (Author) - Creighton University
Kirk Beisel (Author) - Department of Biomedical Sciences
Yi Li (Author) - Creighton University;Capital Medical University
David Z. He (Author) - Department of Biomedical Sciences
Publication Details: Cell Reports, Vol.39(2), 110665
Series: 39
Grant note: 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. We would like to thank Ms. Celia Bloom for designing and creating the graphic abstract. D.H. designed experiments and wrote the manuscript with K.G. and Y.L. H.L. and D.H. performed imaging and cellular physiology experiments. H.L. and Y.L. performed auditory function experiments in vivo and examined HC morphology. H.L. and K.G. prepared HC samples for RNA-seq. K.G. L.C. H.J.H. T.A.C. G.A.K. K.W.B. and D.H. analyzed data and performed smFISH experiments. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. We worked to ensure sex balance in the selection of non-human subjects. One or more of the authors of this paper self-identifies as an underrepresented ethnic minority in science. While citing references scientifically relevant for this work, we also actively worked to promote gender balance in our reference list. Funding Information: 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. We would like to thank Ms. Celia Bloom for designing and creating the graphic abstract.
Identifiers: 991005930855002656
Academic Unit: Biomedical Sciences
Language: English
Resource Type: Journal article