Details
- Autor(en) / Beteiligte
- Titel
- TOR Signaling and Rapamycin Influence Longevity by Regulating SKN-1/Nrf and DAF-16/FoxO
- Ist Teil von
- Cell metabolism, 2012-05, Vol.15 (5), p.713-724
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2012
- Link zum Volltext
- Quelle
- EZB Electronic Journals Library
- Beschreibungen/Notizen
- 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. [Display omitted] ► SKN-1/Nrf mediates longevity effects of TORC1, TORC2, and rapamycin ► TOR signaling suppresses transcription mediated by SKN-1/Nrf and DAF-16/FoxO ► Rapamycin provides DAF-16/FoxO-independent longevity by inhibiting TORC1 and TORC2 ► The IIS and TOR growth pathways influence aging by regulating DAF-16 and SKN-1
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1550-4131eISSN: 1932-7420DOI: 10.1016/j.cmet.2012.04.007Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3348514
- Format
- –
- Schlagworte
- Animals, Caenorhabditis elegans, Caenorhabditis elegans Proteins - genetics, Caenorhabditis elegans Proteins - metabolism, DNA-Binding Proteins - genetics, DNA-Binding Proteins - metabolism, Forkhead Transcription Factors, Insulin-Like Growth Factor I - genetics, Insulin-Like Growth Factor I - metabolism, Longevity - drug effects, Longevity - genetics, Male, Mice, Signal Transduction - drug effects, Sirolimus - pharmacology, TOR Serine-Threonine Kinases - antagonists & inhibitors, TOR Serine-Threonine Kinases - genetics, TOR Serine-Threonine Kinases - metabolism, Trans-Activators - genetics, Trans-Activators - metabolism, Transcription Factors - genetics, Transcription Factors - metabolism, Transcription, Genetic - drug effects