eIF4E function in somatic cells modulates ageing in Caenorhabditis elegans

被引:267
作者
Syntichaki, Popi [1 ]
Troulinaki, Kostoula [1 ]
Tavernarakis, Nektarios [1 ]
机构
[1] Fdn Res & Technol Hellas, Inst Mol Biol & Biotechnol, Iraklion 71110, Crete, Greece
关键词
D O I
10.1038/nature05603
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Regulation of protein synthesis is critical for cell growth and maintenance. Ageing in many organisms, including humans, is accompanied by marked alterations in both general and specific protein synthesis(1). Whether these alterations are simply a corollary of the ageing process or have a causative role in senescent decline remains unclear. An array of protein factors facilitates the tight control of messenger RNA translation initiation(2). The eukaryotic initiation factor 4E (eIF4E), which binds the 7-monomethyl guanosine cap at the 5' end of all nuclear mRNAs, is a principal regulator of protein synthesis(3). Here we show that loss of a specific eIF4E isoform (IFE-2) that functions in somatic tissues(4) reduces global protein synthesis, protects from oxidative stress and extends lifespan in Caenorhabditis elegans. Lifespan extension is independent of the forkhead transcription factor DAF-16, which mediates the effects of the insulin-like signalling pathway on ageing. Furthermore, IFE-2 deficiency further extends the lifespan of long-lived age and daf nematode mutants. Similarly, lack of IFE-2 enhances the long-lived phenotype of clk and dietary-restricted eat mutant animals. Knockdown of target of rapamycin ( TOR), a phosphatidylinositol kinase-related kinase that controls protein synthesis in response to nutrient cues, further increases the longevity of ife-2 mutants. Thus, signalling via eIF4E in the soma is a newly discovered pathway influencing ageing in C. elegans.
引用
收藏
页码:922 / 926
页数:5
相关论文
共 32 条
[1]   MRT-2 checkpoint protein is required for germline immortality and telomere replication in C-elegans [J].
Ahmed, S ;
Hodgkin, J .
NATURE, 2000, 403 (6766) :159-164
[2]  
Amiri A, 2001, DEVELOPMENT, V128, P3899
[3]   Drosophila Lk6 kinase controls phosphorylation of eukaryotic translation initiation factor 4E and promotes normal growth and development [J].
Arquier, N ;
Bourouis, M ;
Colombani, J ;
Léopold, P .
CURRENT BIOLOGY, 2005, 15 (01) :19-23
[4]  
BEANAN MJ, 1992, DEVELOPMENT, V116, P755
[5]   Molecular mechanisms of translational control [J].
Gebauer, F ;
Hentze, MW .
NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2004, 5 (10) :827-835
[6]   eIF4 initiation factors: Effectors of mRNA recruitment to ribosomes and regulators of translation [J].
Gingras, AC ;
Raught, B ;
Sonenberg, N .
ANNUAL REVIEW OF BIOCHEMISTRY, 1999, 68 :913-963
[7]  
HANSEN M, 2006, AGEING CELL
[8]   A mutation in succinate dehydrogenase cytochrome b causes oxidative stress and ageing in nematodes [J].
Ishii, N ;
Fujii, M ;
Hartman, PS ;
Tsuda, M ;
Yasuda, K ;
Senoo-Matsuda, N ;
Yanase, S ;
Ayusawa, D ;
Suzuki, K .
NATURE, 1998, 394 (6694) :694-697
[9]   The TOR pathway interacts with the insulin signaling pathway to regulate C. elegans larval development, metabolism and life span [J].
Jia, K ;
Chen, D ;
Riddle, DL .
DEVELOPMENT, 2004, 131 (16) :3897-3906
[10]   Functional characterization of five eIF4E isoforms in Caenorhabditis elegans [J].
Keiper, BD ;
Lamphear, BJ ;
Deshpande, AM ;
Jankowska-Anyszka, M ;
Aamodt, EJ ;
Blumenthal, T ;
Rhoads, RE .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (14) :10590-10596