title: Histone demethylase UTX-1 regulates C. elegans life span by targeting the insulin/IGF-1 signaling pathway.
abstract: Epigenetic modifications are thought to be important for gene expression changes during development and aging. However, besides the Sir2 histone deacetylase in somatic tissues and H3K4 trimethylation in germlines, there is scant evidence implicating epigenetic regulations in aging. The insulin/IGF-1 signaling (IIS) pathway is a major life span regulatory pathway. Here, we show that progressive increases in gene expression and loss of H3K27me3 on IIS components are due, at least in part, to increased activity of the H3K27 demethylase UTX-1 during aging. RNAi of the utx-1 gene extended the mean life span of C. elegans by ~30%, dependent on DAF-16 activity and not additive in daf-2 mutants. The loss of utx-1 increased H3K27me3 on the Igf1r/daf-2 gene and decreased IIS activity, leading to a more "naive" epigenetic state. Like stem cell reprogramming, our results suggest that reestablishment of epigenetic marks lost during aging might help "reset" the developmental age of animal cells.
authors.affiliation: Chinese Academy of Sciences Key Laboratory of Computational Biology, Chinese Academy of Sciences-Max Planck Partner Institute for Computational Biology, China.
authors.forename: Chunyu
authors.initials: C
authors.lastname: Jin
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Green
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Yu
authors.forename: Xia
authors.initials: X
authors.lastname: Tang
authors.forename: Dali
authors.initials: D
authors.lastname: Han
authors.forename: Bo
authors.initials: B
authors.lastname: Xian
authors.forename: Dan
authors.initials: D
authors.lastname: Wang
authors.forename: Xinxin
authors.initials: X
authors.lastname: Huang
authors.forename: Xiongwen
authors.initials: X
authors.lastname: Cao
authors.forename: Zheng
authors.initials: Z
authors.lastname: Yan
authors.forename: Lei
authors.initials: L
authors.lastname: Hou
authors.forename: Jiancheng
authors.initials: J
authors.lastname: Liu
authors.forename: Nicholas
authors.initials: N
authors.lastname: Shukeir
authors.forename: Philipp
authors.initials: P
authors.lastname: Khaitovich
authors.forename: Charlie D
authors.initials: CD
authors.lastname: Chen
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.forename: Thomas
authors.initials: T
authors.lastname: Jenuwein
authors.forename: Jing-Dong J
authors.initials: JD
authors.lastname: Han
mesh_terms: D000375:Aging; D000818:Animals; D017173:Caenorhabditis elegans / Q000201:enzymology* / Q000235:genetics; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D051858:Forkhead Transcription Factors; D056466:Histone Demethylases / Q000235:genetics / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering; D011972:Receptor, Insulin / Q000235:genetics; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D051858:Forkhead Transcription Factors; D007328:Insulin; D034741:RNA, Small Interfering; D014157:Transcription Factors; C108831:daf-16 protein, C elegans; D007334:Insulin-Like Growth Factor I; D056466:Histone Demethylases; C107483:DAF-2 protein, C elegans; D011972:Receptor, Insulin