Authors: 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
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.Keywords: *Aging; Animals; Caenorhabditis elegans/*enzymology/genetics; Caenorhabditis elegans Proteins/genetics/metabolism; Down-Regulation; Histone Demethylases/genetics/*metabolism; Insulin/metabolism; Insulin-Like Growth Factor I/metabolism; RNA Interference; RNA, Small Interfering; Receptor, Insulin/genetics; *Signal Transduction; Transcription Factors/metabolism
Journal: Cell metabolism
Date: Aug. 2, 2011
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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 (2011) Histone demethylase UTX-1 regulates C. elegans life span by targeting the insulin/IGF-1 signaling pathway. Cell metabolism 14: 161-72.