AI Article Synopsis
- The TOR kinase is vital for growth and is linked to aging and diseases, with its impact on lifespan being significant for understanding aging mechanisms.
- Inhibition of TORC1 in the roundworm C. elegans leads to activation of protective genes by the transcription factors SKN-1/Nrf and DAF-16/FoxO, resulting in increased stress resistance and longer life spans.
- Treatments like rapamycin also enhance lifespan in C. elegans and mice, primarily relying on SKN-1, thereby suggesting that the relationship between growth signals and longevity is influenced by these transcription factors through different signaling pathways.
Article Abstract
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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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3348514 | PMC |
| http://dx.doi.org/10.1016/j.cmet.2012.04.007 | DOI Listing |
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