drr-2 encodes an eIF4H that acts downstream of TOR in diet-restriction-induced longevity of C. elegans
dc.contributor.author | Ching, Tsui-Ting | en_US |
dc.contributor.author | Paal, Alisha B. | en_US |
dc.contributor.author | Mehta, Avni | en_US |
dc.contributor.author | Zhong, Linda | en_US |
dc.contributor.author | Hsu, Ao-Lin | en_US |
dc.date.accessioned | 2011-01-31T17:46:07Z | |
dc.date.available | 2011-10-03T17:19:14Z | en_US |
dc.date.issued | 2010-08 | en_US |
dc.identifier.citation | Ching, Tsui-Ting; Paal, Alisha B.; Mehta, Avni; Zhong, Linda; Hsu, Ao-Lin; (2010). " drr-2 encodes an eIF4H that acts downstream of TOR in diet-restriction-induced longevity of C. elegans ." Aging Cell 9(4): 545-557. <http://hdl.handle.net/2027.42/79256> | en_US |
dc.identifier.issn | 1474-9718 | en_US |
dc.identifier.issn | 1474-9726 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/79256 | |
dc.description.abstract | 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. | en_US |
dc.format.extent | 2913709 bytes | |
dc.format.extent | 964338 bytes | |
dc.format.extent | 3106 bytes | |
dc.format.mimetype | application/pdf | |
dc.format.mimetype | application/pdf | |
dc.format.mimetype | text/plain | |
dc.publisher | Blackwell Publishing Ltd | en_US |
dc.subject.other | Aging | en_US |
dc.subject.other | Longevity | en_US |
dc.subject.other | Caenorhabditis Elegans | en_US |
dc.subject.other | Dietary Restriction | en_US |
dc.subject.other | MRNA Translation | en_US |
dc.subject.other | TOR | en_US |
dc.subject.other | DRR-2 | en_US |
dc.title | drr-2 encodes an eIF4H that acts downstream of TOR in diet-restriction-induced longevity of C. elegans | en_US |
dc.type | Article | en_US |
dc.rights.robots | IndexNoFollow | en_US |
dc.subject.hlbsecondlevel | Molecular, Cellular and Developmental Biology | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI 48109, USA | en_US |
dc.contributor.affiliationother | Division of Geriatric Medicine, Department of Internal Medicine | en_US |
dc.identifier.pmid | 20456299 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/79256/1/ACEL_580_sm_tableS1-3.pdf | |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/79256/2/j.1474-9726.2010.00580.x.pdf | |
dc.identifier.doi | 10.1111/j.1474-9726.2010.00580.x | en_US |
dc.identifier.source | Aging Cell | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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