Vitamin C alleviates aging defects in a stem cell model for Werner syndrome.
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.
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.
Ying
Y
Li
Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City, IA, 52242, USA.
Weizhou
W
Zhang
Department of Gynecology and Obstetrics, Peking University Third Hospital, Beijing, 100191, China.
Liang
L
Chang
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.
Yan
Y
Han
The Key Laboratory of Geriatrics, Beijing Hospital & Beijing Institute of Geriatrics, Ministry of Health, Beijing, 100730, China.
Liang
L
Sun
Department of Pediatrics, Beijing Shijitan Hospital Capital Medical University, Peking University Ninth School of Clinical Medicine, Beijing, 100038, China.
Xiaojun
X
Gong
Department of Pediatrics, Beijing Shijitan Hospital Capital Medical University, Peking University Ninth School of Clinical Medicine, Beijing, 100038, China.
Hong
H
Tang
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.
Zunpeng
Z
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.
Huichao
H
Deng
State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China.
Yanxia
Y
Ye
State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China.
Yu
Y
Wang
The Key Laboratory of Geriatrics, Beijing Hospital & Beijing Institute of Geriatrics, Ministry of Health, Beijing, 100730, China.
Jian
J
Li
Department of Gynecology and Obstetrics, Peking University Third Hospital, Beijing, 100191, China.
Jie
J
Qiao
University of Chinese Academy of Sciences, Beijing, 100049, China. qujing@ioz.ac.cn.|State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China. qujing@ioz.ac.cn.
Jing
J
Qu
National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China. weiqizhang@aliyun.com.|FSU-CAS Innovation Institute, Foshan University, Foshan, 528000, China. weiqizhang@aliyun.com.
Weiqi
W
Zhang
National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China. ghliu@ibp.ac.cn.|University of Chinese Academy of Sciences, Beijing, 100049, China. ghliu@ibp.ac.cn.|FSU-CAS Innovation Institute, Foshan University, Foshan, 528000, China. ghliu@ibp.ac.cn.|Beijing Institute for Brain Disorders, Beijing, 100069, China. ghliu@ibp.ac.cn.
Guang-Hui
GH
Liu
D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D002460:Cell Line; D016922:Cellular Senescence / Q000187:drug effects*; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects; D004261:DNA Replication / Q000187:drug effects; D004195:Disease Models, Animal; D006570:Heterochromatin / Q000378:metabolism / Q000473:pathology; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D034881:Nuclear Lamina / Q000378:metabolism / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism; D059505:Telomere Homeostasis / Q000187:drug effects; D014898:Werner Syndrome / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*
D006570:Heterochromatin; D017382:Reactive Oxygen Species; D001205:Ascorbic Acid
Vitamin C; Werner syndrome; aging; stem cell