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 previously reported that Vitamin C (VC) is a rejuvenating factor for WS hMSCs by altering the expression of genes involved in chromatin condensation, cell cycle regulation, DNA replication, and DNA damage repair pathways (Li et al., 2016b) . Here, we performed a conjoint analysis of RNA-seq data for Que-and VC-treated WS hMSCs to compare and contrast the underlying mechanisms of their geroprotective effects. Firstly, the upregulated and downregulated genes in WS hMSCs compared to WT hMSCs were reversed by either Que or VC treatment ( Fig. 8A and 8B ). We further analyzed the upregulated genes in Que-and VC-treated WS hMSCs. Among these genes, 333 were specific to Que treatment and 721 to VC treatment, with 153 to both Que and VC treatment (Fig. 8C) . Notably, the commonly upregulated genes were enriched in biological process GO terms related to cell cycle, chromatin condensation and anti-oxidation, whereas Que-specific upregulated genes were mostly enriched in response to stimulus and cell homeostasis and the VC-specific ones in DNA replication, DNA repair and telomere maintenance (Fig. 8D) . Thus, these data reveal the major commonalities in the mechanisms by which Que and VC alleviated aging phenotypes in WS hMSCs.