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02804 am a22004093u 4500 |
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91527 |
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|a dc
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|a Robida-Stubbs, Stacey
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|a Massachusetts Institute of Technology. Department of Biology
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|a Whitehead Institute for Biomedical Research
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|a Koch Institute for Integrative Cancer Research at MIT
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|a Lamming, Dudley W.
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|a Sabatini, David M.
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|a Glover-Cutter, Kira
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|a Lamming, Dudley W.
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|a Mizunuma, Masaki
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|a Narasimhan, Sri Devi
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|a Neumann-Haefelin, Elke
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|a Sabatini, David M.
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|a Blackwell, T. Keith
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|a Lamming, Dudley W.
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|a Sabatini, David
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|a TOR Signaling and Rapamycin Influence Longevity by Regulating SKN-1/Nrf and DAF-16/FoxO
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|b Elsevier,
|c 2014-11-12T13:50:59Z.
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|z Get fulltext
|u http://hdl.handle.net/1721.1/91527
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|a The TOR kinase, which is present in the functionally distinct complexes TORC1 and TORC2, is essential for growth but associated with disease and aging. Elucidation of how TOR influences life span will identify mechanisms of fundamental importance in aging and TOR functions. Here we show that when TORC1 is inhibited genetically in C. elegans, SKN-1/Nrf, and DAF-16/FoxO activate protective genes, and increase stress resistance and longevity. SKN-1 also upregulates TORC1 pathway gene expression in a feedback loop. Rapamycin triggers a similar protective response in C. elegans and mice, but increases worm life span dependent upon SKN-1 and not DAF-16, apparently by interfering with TORC2 along with TORC1. TORC1, TORC2, and insulin/IGF-1-like signaling regulate SKN-1 activity through different mechanisms. We conclude that modulation of SKN-1/Nrf and DAF-16/FoxO may be generally important in the effects of TOR signaling in vivo and that these transcription factors mediate an opposing relationship between growth signals and longevity.
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|a National Institutes of Health (U.S.) (Grant CA129105)
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|a Ellison Medical Foundation
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|a American Federation for Aging Research
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|a Starr Foundation
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|a David H. Koch Institute for Integrative Cancer Research at MIT. Frontier Research Program
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|a National Institute of Diabetes and Digestive and Kidney Diseases (U.S.) (DRC Grant)
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|a National Institutes of Health (U.S.) (Ruth L. Kirschstein National Research Service Award) (F32 Postdoctoral Fellowship)
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|a American Diabetes Association (Fellowship)
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|a en_US
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|a Article
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|t Cell Metabolism
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