eIF4E function in somatic cells modulates ageing in Caenorhabditis elegans

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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 synthesis1. 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 initiation2. 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 synthesis3. Here we show that loss of a specific eIF4E isoform (IFE-2) that functions in somatic tissues4reduces global protein synthesis, protects from oxidative stress and extends lifespan inCaenorhabditis 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-livedageanddafnematode mutants. Similarly, lack of IFE-2 enhances the long-lived phenotype ofclkand dietary-restrictedeatmutant 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 ofife-2mutants. Thus, signalling via eIF4E in the soma is a newly discovered pathway influencing ageing inC. elegans.

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