Chemical screen identifies a geroprotective role of quercetin in premature aging

Geng, Lingling; Liu, Zunpeng; Zhang, Weiqi; Li, Wei; Wu, Zeming; Wang, Wei; Ren, Ruotong; Su, Yao; Wang, Peichang; Sun, Liang; Ju, Zhenyu; Chan, Piu; Song, Moshi; Qu, Jing; Liu, Guang-Hui

We have recently established a platform of Werner syndrome (WS) and Hutchinson-Gilford progeria syndrome (HGPS) hMSCs for studying premature and physiological aging (Fang et al., 2018; Kubben et al., 2016; Li et al., 2016b; Wu et al., 2018; Yang et al., 2017; Zhang et al., 2015) . Here, we took advantage of this platform and screened for natural product compounds capable of alleviating premature senescence (Fig. 1A) . A total of 133 natural products (Table S1) were evaluated using WS hMSCs through a short-term treatment of each compound at 1 μmol/L for seven days. The effect on cell proliferation by each compound was evaluated by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assay and ten compounds including quercetin dihydrate (referred to as quercetin, Que), chrysophanic acid, licochalcone A, luteolin, formononetin, honokiol, berberine HCl, kaempferol, bergenin and synephrine ( Fig. 1B and Table S1 ) with at least 15% higher cell proliferative ability than that of the vehicle control (DMSO) were identified. These ten compounds were further evaluated through a long-term treatment at different concentrations for 30 days (Fig. 1A-C) . Que was selected due to its leading effects for further studies.