Vitamin C alleviates aging defects in a stem cell model for Werner syndrome.
10.1007/s13238-016-0278-1
- Author:
Ying LI
1
;
Weizhou ZHANG
2
;
Liang CHANG
3
;
Yan HAN
1
;
Liang SUN
4
;
Xiaojun GONG
5
;
Hong TANG
5
;
Zunpeng LIU
1
;
Huichao DENG
1
;
Yanxia YE
6
;
Yu WANG
6
;
Jian LI
4
;
Jie QIAO
3
;
Jing QU
7
;
Weiqi ZHANG
8
;
Guang-Hui LIU
9
Author Information
1. National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
2. Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City, IA, 52242, USA.
3. Department of Gynecology and Obstetrics, Peking University Third Hospital, Beijing, 100191, China.
4. The Key Laboratory of Geriatrics, Beijing Hospital & Beijing Institute of Geriatrics, Ministry of Health, Beijing, 100730, China.
5. Department of Pediatrics, Beijing Shijitan Hospital Capital Medical University, Peking University Ninth School of Clinical Medicine, Beijing, 100038, China.
6. State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China.
7. University of Chinese Academy of Sciences, Beijing, 100049, China. qujing@ioz.ac.cn.
8. National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China. weiqizhang@aliyun.com.
9. National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China. ghliu@ibp.ac.cn.
- Publication Type:Journal Article
- Keywords:
Vitamin C;
Werner syndrome;
aging;
stem cell
- MeSH:
Animals;
Ascorbic Acid;
pharmacology;
Cell Cycle Checkpoints;
drug effects;
Cell Line;
Cellular Senescence;
drug effects;
DNA Damage;
DNA Repair;
drug effects;
DNA Replication;
drug effects;
Disease Models, Animal;
Heterochromatin;
metabolism;
pathology;
Humans;
Mesenchymal Stem Cells;
metabolism;
pathology;
Mice;
Nuclear Lamina;
metabolism;
pathology;
Reactive Oxygen Species;
metabolism;
Telomere Homeostasis;
drug effects;
Werner Syndrome;
drug therapy;
genetics;
metabolism
- From:
Protein & Cell
2016;7(7):478-488
- CountryChina
- Language:English
-
Abstract:
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, telomere 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.
