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  Histone Demethylase UTX-1 Regulates C.elegans Life Span by Targeting the Insulin/IGF-1 Signaling Pathway

Jin, C., Li, J., Green, C. D., Yu, X., Tang, X., Han, D., et al. (2011). Histone Demethylase UTX-1 Regulates C.elegans Life Span by Targeting the Insulin/IGF-1 Signaling Pathway. Cell Metabolism, 14, 161-172. doi:10.1016/j.cmet.2011.07.001.

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 Creators:
Jin, Chunyu1, Author
Li, Jing1, Author
Green, Christopher D.1, Author
Yu, Xiaoming1, Author
Tang, Xia1, Author
Han, Dali1, Author
Xian, Bo1, Author
Wang, Dan1, Author
Huang, Xinxin1, Author
Cao, Xiongwen1, Author
Yan, Zheng1, Author
Hou, Lei1, Author
Liu, Jiancheng1, Author
Shukeir, Nicholas2, Author              
Khaitovich, Philipp1, Author
Chen, Charlie D.1, Author
Zhang, Hong1, Author
Jenuwein, Thomas2, Author              
Han, Jing-dong J.1, Author
Affiliations:
1External Organizations, ou_persistent22              
2Department of Epigenetics, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_2243644              

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 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.

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Language(s): eng - English
 Dates: 2011-08-03
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1016/j.cmet.2011.07.001
 Degree: -

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Title: Cell Metabolism
  Other : Cell Metabolism
Source Genre: Journal
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Publ. Info: Cambridge, MA : Cell Press
Pages: - Volume / Issue: 14 Sequence Number: - Start / End Page: 161 - 172 Identifier: ISSN: 1550-4131
CoNE: https://pure.mpg.de/cone/journals/resource/111088195284928