Chemical screen identifies a geroprotective role of quercetin in premature aging.

Chemical screen identifies a geroprotective role of quercetin in premature aging.
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化学筛选确定了槲皮素在过早衰老中的老年保护作用。

DOI:
10.1007/s13238-018-0567-y
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发表时间:
2019-06
期刊:
影响因子:
21.1
通讯作者:
Liu GH
Liu GH
中科院分区:
生物学1区
文献类型:
--
作者:
Geng L;Liu Z;Zhang W;Li W;Wu Z;Wang W;Ren R;Su Y;Wang P;Sun L;Ju Z;Chan P;Song M;Qu J;Liu GH

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衰老会增加各种疾病的风险。衰老研究的主要目标是找到减缓衰老和缓解衰老相关疾病的疗法。在这项研究中,我们利用维尔纳综合征 (WS) 人间充质干细胞 (hMSC)(我们最近建立的一种过早衰老模型)筛选了具有老年保护作用的化合物的天然产物库。鉴定出十种候选化合物,并因其主要作用而对槲皮素进行了详细研究。机制研究表明,槲皮素通过增强 WS hMSC 中的细胞增殖和异染色质结构的恢复来减轻衰老。 RNA 测序分析揭示了槲皮素和维生素 C 的衰老保护作用的转录共性和差异。除了 WS hMSC 之外,槲皮素还可以减轻哈钦森-吉尔福德早衰综合征 (HGPS) 和生理老化 hMSC 的细胞衰老。综上所述,我们的研究确定槲皮素是一种衰老保护剂,可防止 hMSC 加速和自然衰老,为治疗与年龄相关的疾病提供潜在的治疗干预。
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.
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