Ageing in many organisms, including humans, is accompanied by marked alterations in both general and specific protein synthesis. The molecular mechanisms underlying these alterations and their role in the ageing process remain unclear. We examined the role of the eukaryotic initiation factor 4E (eIF4E), a key regulator of protein synthesis, in C. elegans ageing. Five eIF4E isoforms with different cap-binding specificity and anatomical expression are encoded in the C. elegans genome (Keiper et al., JBC, 275: 10590). We found that loss of a specific eIF4E isoform, IFE-2 that functions in the soma, extends nematode lifespan. Lifespan extension by IFE-2 depletion is independent of the forkhead transcription factor DAF-16, the downstream effector of the insulin-like signaling pathway. In addition, knockdown of
ife-2 further extends the lifespan of long-lived mutants carrying genetic lesions affecting the insulin/IGF signaling (
age-1 and
daf-2), mitochondrial electron transport chain (
clk-1), dietary restriction (
eat-2) and nutrient-sensing (TOR) pathways. Long-lived IFE-2 mutant animals are more resistant to oxidative stress, compared with wild-type worms. Knockdown of IFE-2 increases resistance to paraquat and extends lifespan of short-lived
mev-1(
kn1) mutants experiencing oxidative stress. Protein synthesis rates are lower in worms lacking IFE-2, compared to wild-type animals. Taken together our results suggest that regulation of a key step of mRNA translation, specifically in the soma modulates ageing in the worm, indicating that adjustment of protein synthesis in response to environmental, reproductive and other cues is important for somatic maintenance.