Molecular and cytological profiling of biological aging of mouse cochlear inner and outer hair cells.
Molecular and cytological profiling of biological aging of mouse cochlear inner and outer hair cells.
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小鼠耳蜗内毛细胞和外毛细胞生物衰老的分子和细胞学分析
DOI：
10.1016/j.celrep.2022.110665
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发表时间：
2022-04-12
期刊：
影响因子：
8.8
通讯作者：
He, David Z.
中科院分区：
文献类型：
--
作者：
Liu, Huizhan;Giffen, Kimberlee P.;Chen, Lei;Henderson, Heidi J.;Cao, Talia A.;Kozeny, Grant A.;Beisel, Kirk W.;Li, Yi;He, David Z.
听力损失（ARHL）对老年人的生活质量产生负面影响。ARHL的普遍原因是机械敏感耳蜗毛细胞（HC）的损失。HC变性的分子和细胞机制仍然知之甚少。使用从年轻和老年小鼠分离的内部和外部HC的RNA-seq转录组学分析，我们表明HC老化与关键分子过程的变化相关，包括转录，DNA损伤，自噬和氧化应激，以及与HC专业化相关的基因。在细胞水平上，HC老化的特征在于静纤毛的丧失、HC索马的收缩和外部HC机械性能的降低，这表明机械转导和耳蜗放大的功能下降先于HC丧失，并导致ARHL。我们的研究揭示了老化HC的分子和细胞学特征，并确定了Sod 1，Sirt 6，Jund和Cbx 3等基因作为改善ARHL的生物标志物和潜在治疗靶点。使用RNA-seq，先进的成像和电生理学，Liu等人揭示了老化耳蜗毛细胞的分子和细胞学特征。他们的研究还表明，机械传导和耳蜗放大的功能下降先于毛细胞损失，并导致与年龄相关的听力损失。
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. Using RNA-seq, advanced imaging, and electrophysiology, Liu et al. reveal molecular and cytological profiles of aging cochlear hair cells. Their study also suggests that a functional decline in mechanotransduction and cochlear amplification precedes hair cell loss and contributes to age-related hearing loss.
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影响因子：
8.8
作者：
Jongkamonwiwat N;Ramirez MA;Edassery S;Wong ACY;Yu J;Abbott T;Pak K;Ryan AF;Savas JN
通讯作者：
Savas JN
影响因子：
64.5
作者：
Davie K;Janssens J;Koldere D;De Waegeneer M;Pech U;Kreft Ł;Aibar S;Makhzami S;Christiaens V;Bravo González-Blas C;Poovathingal S;Hulselmans G;Spanier KI;Moerman T;Vanspauwen B;Geurs S;Voet T;Lammertyn J;Thienpont B;Liu S;Konstantinides N;Fiers M;Verstreken P;Aerts S
通讯作者：
Aerts S
影响因子：
32.4
作者：
Hammond, Timothy R.;Dufort, Connor;Stevens, Beth
通讯作者：
Stevens, Beth
影响因子：
15.9
作者：
Kawashima, Yoshiyuki;Geleoc, Gwenaelle S. G.;Griffith, Andrew J.
通讯作者：
Griffith, Andrew J.
DOI：
10.1093/bioinformatics/btp101
发表时间：
2009-04-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Bindea G;Mlecnik B;Hackl H;Charoentong P;Tosolini M;Kirilovsky A;Fridman WH;Pagès F;Trajanoski Z;Galon J
通讯作者：
Galon J