Drr-2 encodes an eIF4H that acts downstream of TOR in diet-restriction-induced longevity of C. elegans

Tsui Ting Ching, Alisha B. Paal, Avni Mehta, Linda Zhong, Ao Lin Hsu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

42 Scopus citations


Dietary restriction (DR) results in a robust increase in lifespan while maintaining the physiology of much younger animals in a wide range of species. Here, we examine the role of drr-2, a DR-responsive gene recently identified, in determining the longevity of Caenorhabditis elegans. Inhibition of drr-2 has been shown to increase longevity. However, the molecular mechanisms by which drr-2 influences longevity remain unknown. We report here that drr-2 encodes an ortholog of human eukaryotic translation initiation factor 4H (eIF4H), whose function is to mediate the initiation step of mRNA translation. The molecular function of DRR-2 is validated by the association of DRR-2 with polysomes and by the decreased rate of protein synthesis observed in drr-2 knockdown animals. Previous studies have also suggested that DR might trigger a regulated reduction in drr-2 expression to initiate its longevity response. By examining the effect of increasing drr-2 expression on DR animals, we find that drr-2 is essential for a large portion of the longevity response to DR. The nutrient-sensing target of rapamycin (TOR) pathway has been shown to mediate the longevity effects of DR in C. elegans. Results from our genetic analyses suggest that eIF4H/DRR-2 functions downstream of TOR, but in parallel to the S6K/PHA-4 pathway to mediate the lifespan effects of DR. Together, our findings reveal an important role for eIF4H/drr-2 in the TOR-mediated longevity responses to DR.

Original languageEnglish
Pages (from-to)545-557
Number of pages13
JournalAging Cell
Issue number4
StatePublished - Aug 2010


  • Aging
  • Caenorhabditis elegans
  • Dietary restriction
  • DRR-2
  • Longevity
  • mRNA translation
  • TOR


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