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

Protein & Cell 2016年第7期7卷 478-488页

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 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 Pathology Carver 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

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.

关键词： Vitamin C stem cell aging wernersyndrome

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