@article{9cb051dfb463456886fddb3de5670993,
title = "Reducing Hypothalamic Stem Cell Senescence Protects against Aging-Associated Physiological Decline",
abstract = "Age-dependent loss of hypothalamic neural stem cells (htNSCs) is important for the pathological consequences of aging; however, it is unclear what drives the senescence of htNSCs. Here, we report that a long non-coding RNA, Hnscr, is abundantly expressed in the htNSCs of young mice but decreases markedly in middle-aged mice. We show that depletion of Hnscr is sufficient to drive the senescence of htNSCs and aging-like phenotypes in mice. Mechanistically, Hnscr binds to Y-box protein 1 (YB-1) to prevent its degradation and thus the attenuation of transcription of the senescence marker gene p16INK4A. Through molecular docking, we discovered that a naturally occurring small compound, theaflavin 3-gallate, can mimic the activity of Hnscr. Treatment of middle-aged mice with theaflavin 3-gallate reduced the senescence of htNSCs while improving aging-associated pathology. These results point to a mediator of the aging process and one that can be pharmacologically targeted to improve aging-related outcomes.",
keywords = "YB-1, aging, htNSC, hypothalamus, neural stem cells",
author = "Xiao, {Yu Zhong} and Mi Yang and Ye Xiao and Qi Guo and Yan Huang and Li, {Chang Jun} and Dongsheng Cai and Luo, {Xiang Hang}",
note = "Funding Information: The authors thank Prof. Qiurong Ding from Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences (SIBS), and the Chinese Academy of Sciences for providing hPSCs. They also thank Microanaly (Shanghai) Gene Technologies Co. Ltd for the kind help in RNA-seq data analysis. We thank Prof. Wei Li from State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, and the Chinese Academy of Sciences for kind help in reproductive fitness test. This work was supported by grants from the National Natural Science Foundation of China (81930022, 91749105, 81520108008, 81700785, 81801393, 81873643), the Natural Science Foundation of Hunan Province of China (S2019JJQNJJ0681), the innovation-driven project of Central South University (20180033040008), the Science and Technology Development Plan of Hunan Province in 2017 (2017RS3014), and the Talent Plan of Xiangya Hospital at Central South University (grants 52 and 35). Y.Z.X. designed the experiments, generated data, and drafted the manuscript; Y.Z.X. M.Y. and Y.X. carried out majority of the experiments; Q.G. Y.H. and C.J.L. contributed to sample collection; D.C. co-advised the study, guided experiments, and co-wrote the manuscript; X.H.L. supervised the experiments, analyzed results, co-wrote the manuscript, and is the guarantor of this work with full access to all the data in this study, taking the responsibility for data accuracy. The authors declare no competing interests. Funding Information: The authors thank Prof. Qiurong Ding from Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences (SIBS), and the Chinese Academy of Sciences for providing hPSCs. They also thank Microanaly (Shanghai) Gene Technologies Co., Ltd for the kind help in RNA-seq data analysis. We thank Prof. Wei Li from State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, and the Chinese Academy of Sciences for kind help in reproductive fitness test. This work was supported by grants from the National Natural Science Foundation of China ( 81930022 , 91749105 , 81520108008 , 81700785 , 81801393 , 81873643 ), the Natural Science Foundation of Hunan Province of China ( S2019JJQNJJ0681 ), the innovation-driven project of Central South University ( 20180033040008 ), the Science and Technology Development Plan of Hunan Province in 2017 ( 2017RS3014 ), and the Talent Plan of Xiangya Hospital at Central South University (grants 52 and 35). Publisher Copyright: {\textcopyright} 2020 Elsevier Inc.",
year = "2020",
month = mar,
day = "3",
doi = "10.1016/j.cmet.2020.01.002",
language = "English (US)",
volume = "31",
pages = "534--548.e5",
journal = "Cell metabolism",
issn = "1550-4131",
publisher = "Cell Press",
number = "3",
}