The insulin-like/IGF-1 signaling (IIS) pathway is evolutionarily conserved from yeast to humans (Barbieri et al., 2003). Mutations in the insulin receptor homologue in worms, daf-2, extend lifespan in Caenorhabditis elegans and this phenotype is dependent on the activity of the forkhead transcription factor, DAF-16/FOXO (forkhead box, subgroup O) (Murphy et al., 2003). The small heat shock protein (smHSP) HSP-12.6 is a target of DAF-16/FOXO and is implicated to influence lifespan (Murphy et al., 2003). To monitor HSP-12.6 expression in vivo, a transgenic strain carrying a translation fusion of phsp-12.6::HSP-12.6::DSRED2 was constructed. Using this transgenic mutant, longevity assays were performed and we found that overexpression of HSP-12.6 extends lifespan of the animal while reduction of function of hsp-12.6 by RNAi decreases lifespan. Longevity assay data also suggest that HSP-12.6 requires the transcription factor DAF-16 but not necessarily HSF-1 for its function.
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