Progressive functional deterioration in the cochlea is associated with age-related hearing loss (ARHL). However, the cellular and molecular basis underlying cochlear aging remains largely unknown. Here, we established a dynamic single-cell transcriptomic landscape of mouse cochlear aging, in which we characterized aging-associated transcriptomic changes in 27 different cochlear cell types across five different time points. Overall, our analysis pinpoints loss of proteostasis and elevated apoptosis as the hallmark features of cochlear aging, highlights unexpected age-related transcriptional fluctuations in intermediate cells localized in the stria vascularis (SV) and demonstrates that upregulation of endoplasmic reticulum (ER) chaperon protein HSP90AA1 mitigates ER stress-induced damages associated with aging. Our work suggests that targeting unfolded protein response pathways may help alleviate aging-related SV atrophy and hence delay the progression of ARHL.
基金：
This work was supported by the National Key Research and
Development Program of China (No. 2020YFA0804000), the Strategic
Priority Research Program of the Chinese Academy of Sciences
(No. XDA16000000), the National Natural Science Foundation of
China (Nos. 82192863, 81921006, 92149301, 92168201, 91949209,
92049304, 82125011, 82122024, 82071588, 92049116, 32121001,
32000500, 82030029, 81970882, 31900523, 82271600, 32200610, and
81861168034), the National Key Research and Development Program
of China (Nos. 2018YFC2000100, 2021ZD0202400, 2020YFA0112200,
2018YFA0107203, 2021YFF1201005, and 2019YFA0110100), the
Program of the Beijing Natural Science Foundation (No. Z190019),
CAS Project for Young Scientists in Basic Research (No. YSBR-076
and YSBR-012), the Key Research Program of the Chinese Academy
of Sciences (No. KFZD-SW-221), K. C. Wong Education Foundation
(Nos. GJTD-2019-06 and GJTD-2019-08), Youth Innovation Promotion
Association of CAS (Nos. 2021078, 2022083, and E1CAZW0401), Young
Elite Scientists Sponsorship Program by CAST (Nos. YESS20200012
and YESS20210002), the State Key Laboratory of Stem Cell and
Reproductive Biology, the State Key Laboratory of Membrane Biology,
the Tencent Foundation (No. 2021-1045), the Informatization Plan of
Chinese Academy of Sciences (Nos. CAS-WX2021SF-0301 and CASWX2022SDC-
XK14), the Pilot Project for Public Welfare Development
and Reform of Beijing-affiliated Medical Research Institutes (No.
11000022T000000461062), Natural Science Foundation from
Jiangsu Province (No. BE2019711), Shenzhen Fundamental Research
Program (No. JCYJ20190814093401920), and Open Research Fund of State Key Laboratory of Genetic Engineering, Fudan University (No.
SKLGE-2109).
生物学