%0 Journal Article %T Epigenetic silencing of Lgr5 induces senescence of intestinal epithelial organoids during the process of aging %A Hidetsugu Saito %A Kazuki Nogami %A Masaki Kimura %A Ryoei Uchida %A Toshiaki Nakaoka %A Toshihide Muramatsu %A Yasuhiro Kawase %A Yohei Kajiyama %A Yoshimasa Saito %A Yukana Suzuki %J Archive of "NPJ Aging and Mechanisms of Disease". %D 2018 %R 10.1038/s41514-018-0031-5 %X Senescence-related changes in intestinal epithelial organoids derived from aged mice. a Representative images of a single stem cell expanding into organoids derived from intestinal epithelia of young (4 weeks) and aged (54 weeks) mice. Scale bars: 250£¿¦Ìm. b Success rate of organoid establishment from young mice (4¨C27 weeks, n£¿=£¿10) and aged mice (54¨C130 weeks, n£¿=£¿15). We defined the establishment of organoids as successful if it was possible to culture them over 5 passages. *p£¿<£¿0.05. c TUNEL assay for detection of apoptosis. Apoptotic cell death was observed in intestinal epithelial organoids after trypsin treatment without the Rho-kinase inhibitor Y-27632. Scale bars: 100£¿¦Ìm. d Cell numbers in intestinal epithelial organoids derived from young (4 weeks) and aged (54 weeks) mice during the culture course. Results of 5 experiments were plotted as mean£¿¡À£¿SD. ***p£¿<£¿0.001. e Relative expression levels of Cdkn1a (p21) and Cdkn2a (p16) and cell cycle analysis of intestinal epithelial organoids established from young (4 weeks) and aged (54 weeks) mice. Results of 5 experiments were plotted as mean£¿¡À£¿SD. *p£¿<£¿0.05, **p£¿<£¿0.01. f The numbers of intestinal crypts in young (10 weeks) and aged (120 weeks) mice. HE staining of intestinal crypts in young and aged mice are shown. Scale bars: 100£¿¦Ìm. The number of intestinal crypts (/mm) was significantly decreased in aged mice in comparison to young mice. Results of 5 experiments were plotted as mean£¿¡À£¿SD. *p£¿<£¿0.0 %U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6279747/