Inhibition of mRNA translation extends lifespan in Caenorhabditis elegans

被引:387
作者
Pan, Kally Z. [1 ]
Palter, Julia E. [1 ]
Rogers, Aric N. [1 ]
Olsen, Anders [1 ]
Chen, Di [1 ]
Lithgow, Gordon J. [1 ]
Kapahi, Pankaj [1 ]
机构
[1] Buck Inst Age Res, Novato, CA 94945 USA
关键词
C; elegans; eIF4G; lifespan; mRNA translation; protein synthesis; S6; kinase;
D O I
10.1111/j.1474-9726.2006.00266.x
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Protein synthesis is a regulated cellular process that links nutrients in the environment to organismal growth and development. Here we examine the role of genes that regulate mRNA translation in determining growth, reproduction, stress resistance and lifespan. Translational control of protein synthesis by regulators such as the cap-binding complex and S6 kinase play an important role during growth. We observe that inhibition of various genes in the translation initiation complex including ifg-1, the worm homologue of eIF4G, which is a scaffold protein in the cap-binding complex; and rsks-1, the worm homologue of S6 kinase, results in lifespan extension in Caenorhabditis elegans. Inhibition of ifg-1 or rsks-1 also slows development, reduces fecundity and increases resistance to starvation. A reduction in ifg-1 expression in dauers was also observed, suggesting an inhibition of protein translation during the dauer state. Thus, mRNA translation exerts pleiotropic effects on growth, reproduction, stress resistance and lifespan in C. elegans.
引用
收藏
页码:111 / 119
页数:9
相关论文
共 43 条
[1]  
[Anonymous], 1997, C ELEGANS
[2]   Healthy animals with extreme longevity [J].
Arantes-Oliveira, N ;
Berman, JR ;
Kenyon, C .
SCIENCE, 2003, 302 (5645) :611-611
[3]   PHARYNGEAL PUMPING CONTINUES AFTER LASER KILLING OF THE PHARYNGEAL NERVOUS-SYSTEM OF C-ELEGANS [J].
AVERY, L ;
HORVITZ, R .
NEURON, 1989, 3 (04) :473-485
[4]   The TOR (target of rapamycin) signal transduction pathway regulates the stability of translation initiation factor eIF4G in the yeast Saccharomyces cerevisiae [J].
Berset, C ;
Trachsel, H ;
Altmann, M .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (08) :4264-4269
[5]   Isolation of long-lived mutants in Caenorhabditis elegans using selection for resistance to juglone [J].
De Castro, E ;
De Castro, SH ;
Johnson, TE .
FREE RADICAL BIOLOGY AND MEDICINE, 2004, 37 (02) :139-145
[6]   Translation of a small subset of Caenorhabditis elegans mRNAs is dependent on a specific eukaryotic translation initiation factor 4E isoform [J].
Dinkova, TD ;
Keiper, BD ;
Korneeva, NL ;
Aamodt, EJ ;
Rhoads, RE .
MOLECULAR AND CELLULAR BIOLOGY, 2005, 25 (01) :100-113
[7]   Structural and functional conservation of the Caenorhabditis elegans timing gene clk-1 [J].
Ewbank, JJ ;
Barnes, TM ;
Lakowski, B ;
Lussier, M ;
Bussey, H ;
Hekimi, S .
SCIENCE, 1997, 275 (5302) :980-983
[8]  
Finch CE., 1990, Longevity, Senescence, and the Genome
[9]   Interpreting interactions between treatments that slow aging [J].
Gems, D ;
Pletcher, S ;
Partridge, L .
AGING CELL, 2002, 1 (01) :1-9
[10]  
Harris Thurl E, 2003, Sci STKE, V2003, pre15