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

doi:10.1007/s13238-016-0278-1

Protein Cell

2016, Vol. 7

Issue (7) : 478-488 https://doi.org/10.1007/s13238-016-0278-1

RESEARCH ARTICLE

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

Ying Li^1,²,Weizhou Zhang⁵,Liang Chang⁴,Yan Han^1,²,Liang Sun⁶,Xiaojun Gong⁹,Hong Tang⁹,Zunpeng Liu^1,²,Huichao Deng^1,²,Yanxia Ye³,Yu Wang³,Jian Li⁶,Jie Qiao⁴,Jing Qu^2,^3,^*(

),Weiqi Zhang^1,^7,^*(

),Guang-Hui Liu^1,^2,^7,^8,^*(

)

¹. National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
². University of Chinese Academy of Sciences, Beijing 100049, China
³. State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China
⁴. Department of Gynecology and Obstetrics, Peking University Third Hospital, Beijing 100191, China
⁵. Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
⁶. The Key Laboratory of Geriatrics, Beijing Hospital & Beijing Institute of Geriatrics, Ministry of Health, Beijing 100730, China
⁷. FSU-CAS Innovation Institute, Foshan University, Foshan 528000, China
⁸. Beijing Institute for Brain Disorders, Beijing 100069, China
⁹. Department of Pediatrics, Beijing Shijitan Hospital Capital Medical University, Peking University Ninth School of Clinical Medicine, Beijing 100038, China

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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 WRNdeficient 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.

Keywords Vitamin C stem cell aging Werner syndrome

Corresponding Author(s): Jing Qu,Weiqi Zhang,Guang-Hui Liu

Issue Date: 18 July 2016

Cite this article:

Ying Li,Weizhou Zhang,Liang Chang, et al. Vitamin C alleviates aging defects in a stem cell model for Werner syndrome[J]. Protein Cell, 2016, 7(7): 478-488.

URL:

https://academic.hep.com.cn/pac/EN/10.1007/s13238-016-0278-1
https://academic.hep.com.cn/pac/EN/Y2016/V7/I7/478

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