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

Que-treated WS hMSCs were able to express hMSCspecific markers including CD73, CD90 and CD105 (Fig. 3A) . Que alleviated the senescent phenotypes of latepassage WS hMSCs, evidenced by decreased senescent markers P16 and P21 (Fig. 3B ), increased telomere length ( Fig. 3C ), increased cell proliferative potential by Ki67 staining (Fig. 3D) , and decreased DNA damage response markers γ-H2AX and 53BP1 (Fig. 3E ). Reactive oxygen species (ROS) production (Labbé et al., 2010) (Fig. 3F) , mRNA levels of proinflammatory cytokine IL-6 ( Fig. 3G ) and cell apoptosis (Fig. 3H) were each suppressed in Quetreated WS hMSCs. In addition, Que-treated WS hMSCs maintained the ability to differentiate towards multiple mesodermal lineages, with enhanced potentials towards osteogenesis and chondrogenesis (Fig. 4A) . Furthermore, Que attenuated the in vivo decay of WS hMSCs implanted into the tibialis anterior muscles of nude mice (Fig. 4B ) and enhanced the vasculogenic ability of WS hMSCs implanted into the fat pads of non-obese diabetic (NOD) scid mice (Fig. 4C ). Taken together, these data suggest that Que alleviated cellular senescence and promoted self-renewal and differentiation abilities in WS hMSCs.