Vitamin C alleviates aging defects in a stem cell model for Werner syndrome

作     者：Ying Li Weizhou Zhang Liang Chang Yan Han Liang Sun Xiaojun Gong Hong Tang Zunpeng Liu Huichao Deng Yanxia Ye Yu Wang Jian Li Jie Qiao Jing Qu Weiqi Zhang Guang-Hui Liu 

作者机构：National Laboratory of Biomacromolecules CAS Center for Excellence in Biomacromolecules Institute of Biophysics Chinese Academy of Sciences Beijing 100101 China University of Chinese Academy of Sciences Beijing 100049 China State Key Laboratory of Stem Cell and Reproductive Biology Institute of Zoology Chinese Academy of Sciences Beijing 100101 China Department of Gynecology and Obstetrics Peking University Third Hospital Beijing 100191 China Department of PathologyCarver College Of Medicine University of lowa lowa City IA 52242 USA The Key Laboratory of Geriatrics Beijing Hospital & Beijing Institute of Geriatrics Ministry of Health Beijing 100730 China FSU-CAS Innovation Institute Foshan University Foshan 528000 China Beijing Institute for Brain Disorders Beijing 100069 China Department of Pediatrics Beijing Shijitan Hospital Capital Medical University Peking University Ninth School of Clinical Medicine Beijing 100038 China 

出 版 物：《Protein & Cell》 (蛋白质与细胞（英文版）)

年 卷 期：2016年第7卷第7期

页      面：478-488页

核心收录：

学科分类：0710[理学-生物学] 0831[工学-生物医学工程（可授工学、理学、医学学位）] 1007[医学-药学(可授医学、理学学位)] 1002[医学-临床医学] 08[工学] 09[农学] 0703[理学-化学] 0901[农学-作物学] 0836[工学-生物工程] 090102[农学-作物遗传育种] 10[医学] 

基　　金：the National Basic Research Program of China (973 Program) (Nos. 2015CB964800 and 2014CB910503)  the Strategic Priority Research Program of the Chinese Academy of Sciences (XDA01020312)  the National High Technology Research and Development Program of China (2015AA020307)  the National Nat- ural Science Foundation of China (Grant Nos. 81330008  31222039  31201111  81371342  81300261  81300677  81271266  81471414  81422017  and 81401159)  the Program of Beijing Municipal Science and Technology Commission (Z151100003915072)  the Beijing Nat- ural Science Foundation (7141005 and 5142016)  the Key Research Program of the Chinese Academy of Sciences (KJZDEW-TZ-L05)  the Thousand Young Talents program of China  Youth Innovation Pro- motion Association of CAS. WZ was supported by NIH grants CA158055  CA200673  and CA203834  the V Scholar award  Breast Cancer Research Award and Oberley Award (National Cancer Insti- tute Award P30CA086862) from Holden Comprehensive Cancer Center at the University of Iowa  and startup fund from the Department of Pathology  University of lowa 

主　　题：Vitamin C stem cell aging Wernersyndrome 

摘      要：Werner syndrome （WS） is a premature aging disorder that mainly affects tissues derived from mesoderm. We have recently developed a novel human WS model using WRN-deficient human mesenchymal stem cells （MSCs）. This model recapitulates many phenotypic features of WS. Based on a screen of a number of chemicals, here we found that Vitamin C exerts most efficient rescue for many features in premature aging as shown in WRN-deficient MSCs, including cell growth arrest, increased reactive oxygen species levels, teiomere attrition, excessive secretion of inflammatory factors, as well as disorganization of nuclear lamina and heterochromatin. Moreover, Vitamin C restores in vivo viability of MSCs in a mouse model. RNA sequencing analysis indicates that Vitamin C alters the expression of a series of genes involved in chromatin condensation, cell cycle regulation, DNA replication, and DNA damage repair pathways in WRN- deficient MSCs. Our results identify Vitamin C as a rejuvenating factor for WS MSCs, which holds the potential of being applied as a novel type of treatment of WS.