Title Vitamin C alleviates aging defects in a stem cell model for Werner syndrome
Authors Li, Ying
Zhang, Weizhou
Chang, Liang
Han, Yan
Sun, Liang
Gong, Xiaojun
Tang, Hong
Liu, Zunpeng
Deng, Huichao
Ye, Yanxia
Wang, Yu
Li, Jian
Qiao, Jie
Qu, Jing
Zhang, Weiqi
Liu, Guang-Hui
Affiliation Chinese Acad Sci, CAS Ctr Excellence Biomacromol, Natl Lab Biomacromol, Inst Biophys, Beijing 100101, Peoples R China.
Univ Chinese Acad Sci, Beijing 100049, Peoples R China.
Chinese Acad Sci, Inst Zool, State Key Lab Stem Cell & Reprod Biol, Beijing 100101, Peoples R China.
Peking Univ, Dept Gynecol & Obstet, Hosp 3, Beijing 100191, Peoples R China.
Univ Iowa, Dept Pathol, Carver Coll Med, Iowa City, IA 52242 USA.
Beijing Hosp, Key Lab Geriatr, Beijing 100730, Peoples R China.
Minist Hlth, Beijing Inst Geriatr, Beijing 100730, Peoples R China.
Foshan Univ, FSU CAS Innovat Inst, Foshan 528000, Peoples R China.
Beijing Inst Brain Disorders, Beijing 100069, Peoples R China.
Peking Univ, Sch Clin Med 9, Dept Pediat, Beijing Shijitan Hosp,Capital Med Univ, Beijing 100038, Peoples R China.
Chinese Acad Sci, CAS Ctr Excellence Biomacromol, Natl Lab Biomacromol, Inst Biophys, Beijing 100101, Peoples R China.
Qu, J
Liu, GH (reprint author), Univ Chinese Acad Sci, Beijing 100049, Peoples R China.
Qu, J (reprint author), Chinese Acad Sci, Inst Zool, State Key Lab Stem Cell & Reprod Biol, Beijing 100101, Peoples R China.
Zhang, WQ
Liu, GH (reprint author), Foshan Univ, FSU CAS Innovat Inst, Foshan 528000, Peoples R China.
Liu, GH (reprint author), Beijing Inst Brain Disorders, Beijing 100069, Peoples R China.
Keywords Vitamin C
stem cell
aging
Werner syndrome
GILFORD PROGERIA SYNDROME
LIFE-SPAN
SENESCENT CELLS
EXPRESSION
IMPROVES
DISEASE
IPSCS
MICE
GENE
INTEGRATION
Issue Date 2016
Publisher PROTEIN & CELL
Citation PROTEIN & CELL.2016,7(7),478-488.
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.
URI http://hdl.handle.net/20.500.11897/433431
ISSN 1674-800X
DOI 10.1007/s13238-016-0278-1
Indexed SCI(E)
PubMed
中国科技核心期刊(ISTIC)
中国科学引文数据库(CSCD)
Appears in Collections: 第三医院
北京世纪坛医院

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