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

Alleviating premature aging by quercetin RESEARCH ARTICLE LMNA G608G/+ mutation into human embryonic stem cells (hESCs) followed by directed differentiation into hMSCs (Kubben et al., 2016; Wu et al., 2018) . DNA sequencing confirmed the presence of heterozygous mutation of LMNA G608G/+ in HGPS hMSCs (Fig. 9A ). The mRNA level and immunostaining intensity of progerin, which is the resultant truncated protein product of mutated LMNA, were decreased in Que-, VC-and VC plus Que-treated HGPS hMSCs ( Fig. 9B and 9C ). The alleviation of cellular senescence by Que, VC, or VC plus Que in HGPS hMSCs was further evidenced by decreased population doubling time (Fig. 9D) , decreased SA-β-Gal positivity (Fig. 9E) , and increased clonal expansion and proliferative ability ( Fig. 9F -H). In addition, the percentage of abnormal nuclei, a cellular hallmark of HGPS, decreased in HGPS hMSCs upon Que treatment (Fig. 9I ). Taken together, these data indicate that Que attenuated accelerated senescence in HGPS hMSCs.