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

Progeroid syndromes are a group of rare genetic disorders characterized by clinical features of premature aging. Werner syndrome (WS) and Hutchinson-Gilford progeria syndrome (HGPS) are two best characterized types of progeria. WS is known as adult progeria, mainly characterized by premature aging pathologies associated with the degeneration of mesodermal tissues, resulting in symptoms such as osteoporosis and atherosclerosis (Opresko et al., 2003; Ozgenc and Loeb, 2006) . WS is caused by mutated WRN gene, resulting in the loss of WRN protein expression. WRN participates in a continuum of cellular processes, spanning from DNA replication, transcription, repair, recombination as well as heterochromatin maintenance at telomeric and centromeric regions, thus pointing WS pathogenesis to genomic and epigenomic instability (Kudlow et al., 2007; Lebel, 2001; Li et al., 2016b; Wu et al., 2018; Zhang et al., 2015) . The other well-studied progeria, HGPS is a devastating incurable disease with an average age of death at 14.6 years (Hennekam Raoul, 2006; Kreienkamp et al., 2016; Ullrich and Gordon, 2015) . It is caused by the accumulation of progerin, a truncated protein encoded by a GGC>GGT (G608G) single-base mutation in LMNA gene instead of the functional nuclear lamina protein Lamin A by wild-type LMNA gene. HGPS patient-derived cells usually exhibit nuclear morphological abnormalities, altered signaling pathways, genomic and epigenetic instability and premature senescence (Burtner and Kennedy, 2010; Kubben et al., 2016; Kudlow et al., 2007; López-Otín et al., 2013; Liu et al., 2011a; Liu et al., 2011b; Polosak et al., 2011; Ren et al., 2017b; Wu et al., 2018; Yang et al., 2014) .