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

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

doi:10.1007/s13238-016-0278-1

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

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

Ying Li, Weizhou Zhang, Liang Chang, Yan Han, Liang Sun, Xiaojun Gong, Hong Tang, Zunpeng Liu, Huichao Deng, Yanxia Ye, …

Protein & cell, Vol.7(7), pp.478-488

07/2016

DOI: 10.1007/s13238-016-0278-1

PMCID: PMC4930768

PMID: 27271327

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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.

Cell Line

DNA Repair - drug effects

Werner Syndrome - drug therapy

Reactive Oxygen Species - metabolism

DNA Replication - drug effects

Humans

Cellular Senescence - drug effects

Mesenchymal Stromal Cells - metabolism

Animals

Heterochromatin - metabolism

Nuclear Lamina - metabolism

Werner Syndrome - metabolism

Cell Cycle Checkpoints - drug effects

Werner Syndrome - genetics

Ascorbic Acid - pharmacology

Mice

DNA Damage

Heterochromatin - pathology

Mesenchymal Stromal Cells - pathology

Nuclear Lamina - pathology

Telomere Homeostasis - drug effects

Disease Models, Animal

Details

Title: Subtitle: Vitamin C alleviates aging defects in a stem cell model for Werner syndrome
Creators: Ying Li - Chinese Academy of Sciences
Weizhou Zhang - Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City, IA, 52242, USA
Liang Chang - Department of Gynecology and Obstetrics, Peking University Third Hospital, Beijing, 100191, China
Yan Han - University of Chinese Academy of Sciences, Beijing, 100049, China
Liang Sun - The Key Laboratory of Geriatrics, Beijing Hospital & Beijing Institute of Geriatrics, Ministry of Health, Beijing, 100730, China
Xiaojun Gong - Department of Pediatrics, Beijing Shijitan Hospital Capital Medical University, Peking University Ninth School of Clinical Medicine, Beijing, 100038, China
Hong Tang - Department of Pediatrics, Beijing Shijitan Hospital Capital Medical University, Peking University Ninth School of Clinical Medicine, Beijing, 100038, China
Zunpeng Liu - University of Chinese Academy of Sciences, Beijing, 100049, China
Huichao Deng - University of Chinese Academy of Sciences, Beijing, 100049, China
Yanxia Ye - State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China
Yu Wang - State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China
Jian Li - The Key Laboratory of Geriatrics, Beijing Hospital & Beijing Institute of Geriatrics, Ministry of Health, Beijing, 100730, China
Jie Qiao - Department of Gynecology and Obstetrics, Peking University Third Hospital, Beijing, 100191, China
Jing Qu - State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China. qujing@ioz.ac.cn
Weiqi Zhang - FSU-CAS Innovation Institute, Foshan University, Foshan, 528000, China. weiqizhang@aliyun.com
Guang-Hui Liu - Beijing Institute for Brain Disorders, Beijing, 100069, China. ghliu@ibp.ac.cn
Resource Type: Journal article
Publication Details: Protein & cell, Vol.7(7), pp.478-488
DOI: 10.1007/s13238-016-0278-1
PMID: 27271327
PMCID: PMC4930768
NLM abbreviation: Protein Cell
ISSN: 1674-800X
eISSN: 1674-8018
Grant note: R00 CA158055 / NCI NIH HHS R01 CA203834 / NCI NIH HHS K99 CA158055 / NCI NIH HHS R01 CA200673 / NCI NIH HHS P30 CA086862 / NCI NIH HHS
Language: English
Date published: 07/2016
Academic Unit: Radiation Oncology
Record Identifier: 9984083273102771

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