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

Protein & cell (2016-06-09)
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
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
L-Ascorbic acid, powder, suitable for cell culture, γ-irradiated
Sigma-Aldrich
(+)-γ-Tocopherol, ≥96% (HPLC)