RRC ID 46131
Author Jin C, Li J, Green CD, Yu X, Tang X, Han D, Xian B, Wang D, Huang X, Cao X, Yan Z, Hou L, Liu J, Shukeir N, Khaitovich P, Chen CD, Zhang H, Jenuwein T, Han JD.
Title Histone demethylase UTX-1 regulates C. elegans life span by targeting the insulin/IGF-1 signaling pathway.
Journal Cell Metab
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.
Volume 14(2)
Pages 161-72
Published 2011-8-3
DOI 10.1016/j.cmet.2011.07.001
PII S1550-4131(11)00262-2
PMID 21803287
MeSH Aging* Animals Caenorhabditis elegans / enzymology* Caenorhabditis elegans / genetics Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism Down-Regulation Forkhead Transcription Factors Histone Demethylases / genetics Histone Demethylases / metabolism* Insulin / metabolism Insulin-Like Growth Factor I / metabolism RNA Interference RNA, Small Interfering Receptor, Insulin / genetics Signal Transduction* Transcription Factors / metabolism
IF 21.567
Times Cited 125
C.elegans tm3118