Attenuation of protein synthesis has been demonstrated to increase lifespan across taxa. Recent findings show that activators of mRNA degradation suppress mRNA translation by targeting mRNAs for storage and decapping in cytoplasmic Processing (P) bodies. We hypothesized that storage and degradation of mRNAs in P bodies may regulate physiological processes such as stress responses and ageing via the control of mRNA translation. We observed that somatic P bodies increase in size and number during ageing in C. elegans. IFE-2, an isoform of the translation initiation factor eIF4E, progressively localizes to P bodies upon stress and during ageing. Loss of the P body factor “enhancer of mRNA decapping” EDC-3 promotes longevity and resistance to stress. EDC-3 mutants display reduced protein synthesis in somatic cells. Furthermore, lack of EDC-3 leads to increased P body formation. Notably, longevity and stress resistance in EDC-3-depleted animals is rescued by neuron-specific EDC-3 expression. We find that the transcription factor SKN-1, which also mediates lifespan extension by eIF4E deficiency in somatic C. elegans tissues, is required for the effects of EDC-3 depletion on stress resistance and lifespan. Further, loss of SKN-1 robustly enhances P body formation in EDC-3 mutants. We conclude that upon mRNA decapping impairment, eIF4E becomes sequestered in P bodies, which in turn downregulates general protein synthesis in the soma, thereby increasing organismal lifespan. Our findings indicate a causative role for P bodies in the regulation of stress resistance and ageing.
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