Vitamin C alleviates aging defects in a stem cell model for Werner syndrome
Protein & Cell
;
(12): 478-488, 2016.
Article
in English
| WPRIM
| ID: wpr-757417
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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Pathology
/
Pharmacology
/
Ascorbic Acid
/
Werner Syndrome
/
DNA Damage
/
Heterochromatin
/
Cell Line
/
Cellular Senescence
/
Reactive Oxygen Species
/
Nuclear Lamina
Type of study:
Prognostic study
Limits:
Animals
/
Humans
Language:
English
Journal:
Protein & Cell
Year:
2016
Type:
Article
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