Vitamin C alleviates aging defects in a stem cell model for Werner syndrome
Protein & Cell
;
(12): 478-488, 2016.
Article
Dans Anglais
| 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.
Texte intégral:
Disponible
Indice:
WPRIM (Pacifique occidental)
Sujet Principal:
Anatomopathologie
/
Pharmacologie
/
Acide ascorbique
/
Syndrome de Werner
/
Altération de l'ADN
/
Hétérochromatine
/
Lignée cellulaire
/
Vieillissement de la cellule
/
Espèces réactives de l'oxygène
/
Lamina nucléaire
Type d'étude:
Étude pronostique
Limites du sujet:
Animaux
/
Humains
langue:
Anglais
Texte intégral:
Protein & Cell
Année:
2016
Type:
Article
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