机构：[1]Advanced Innovation Center for Human Brain Protection, National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital of Capital Medical University, Beijing 100053, China首都医科大学宣武医院衰老与再生研究中心[2]National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China[3]State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China[4]State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China[5]University of Chinese Academy of Sciences, Beijing 100049, China[6]Institute of Stem cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, China[7]Key Laboratory of Regenerative Medicine of Ministry of Education, Institute of Aging and Regenerative Medicine, Jinan University, Guangzhou 510632, China[8]The MOH Key Laboratory of Geriatrics, Beijing Hospital, National Center of Gerontology, Beijing 100730, China
Aging increases the risk of various diseases. The main goal of aging research is to find therapies that attenuate aging and alleviate aging-related diseases. In this study, we screened a natural product library for geroprotective compounds using Werner syndrome (WS) human mesenchymal stem cells (hMSCs), a premature aging model that we recently established. Ten candidate compounds were identified and quercetin was investigated in detail due to its leading effects. Mechanistic studies revealed that quercetin alleviated senescence via the enhancement of cell proliferation and restoration of heterochromatin architecture in WS hMSCs. RNA-sequencing analysis revealed the transcriptional commonalities and differences in the geroprotective effects by quercetin and Vitamin C. Besides WS hMSCs, quercetin also attenuated cellular senescence in Hutchinson-Gilford progeria syndrome (HGPS) and physiological-aging hMSCs. Taken together, our study identifies quercetin as a geroprotective agent against accelerated and natural aging in hMSCs, providing a potential therapeutic intervention for treating age-associated disorders.
基金：
This work was supported by the
National Key Research and Development Program of China
(2017YFA0103304), the Strategic Priority Research Program of the
Chinese Academy of Sciences (XDA16010100), the National Key
Research and Development Program of China (2015CB964800,
2017YFA0102802, 2014CB910503 and 2018YFA0107203), the
National High Technology Research and Development Program of
China (2015AA020307), the National Natural Science Foundation of
China (Grant Nos. 31671429, 91749202, 91749123, 81625009,
81330008, 81371342, 81471414, 81422017, 81601233, 81671377,
31601109, 31601158, 81771515 and 81701388), Program of Beijing
Municipal Science and Technology Commission (Z151100003
915072), Key Research Program of the Chinese Academy of Sciences
(KJZDEW-TZ-L05), Beijing Municipal Commission of Health
and Family Planning (PXM2018_026283_000002), and Advanced
Innovation Center for Human Brain Protection (117212).
第一作者机构：[1]Advanced Innovation Center for Human Brain Protection, National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital of Capital Medical University, Beijing 100053, China[2]National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
共同第一作者：
通讯作者：
通讯机构：[1]Advanced Innovation Center for Human Brain Protection, National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital of Capital Medical University, Beijing 100053, China[2]National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China[3]State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China[4]State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China[5]University of Chinese Academy of Sciences, Beijing 100049, China[6]Institute of Stem cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, China[7]Key Laboratory of Regenerative Medicine of Ministry of Education, Institute of Aging and Regenerative Medicine, Jinan University, Guangzhou 510632, China
推荐引用方式(GB/T 7714)：
Geng Lingling,Liu Zunpeng,Zhang Weiqi,et al.Chemical screen identifies a geroprotective role of quercetin in premature aging[J].PROTEIN & CELL.2019,10(6):417-435.doi:10.1007/s13238-018-0567-y.
APA：
Geng, Lingling,Liu, Zunpeng,Zhang, Weiqi,Li, Wei,Wu, Zeming...&Liu, Guang-Hui.(2019).Chemical screen identifies a geroprotective role of quercetin in premature aging.PROTEIN & CELL,10,(6)
MLA：
Geng, Lingling,et al."Chemical screen identifies a geroprotective role of quercetin in premature aging".PROTEIN & CELL 10..6(2019):417-435
生物学