TOR signaling and rapamycin influence longevity by regulating SKN-1/Nrf and DAF-16/FoxO

Robida-Stubbs S, Glover-Cutter K, Lamming DW, Mizunuma M, Narasimhan SD, Neumann-Haefelin E, Sabatini DM, Blackwell TK · 2012 · Cell metabolism · Atlas ID ROB2012

What this study shows

In C. elegans, genetic TORC1 inhibition extends lifespan through SKN-1/Nrf and DAF-16/FoxO, whereas rapamycin's lifespan effect requires SKN-1 but not DAF-16, apparently because it also hits TORC2.

Abstract

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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.

Read the full abstract on PubMed →

At a glance

Evidence type	A Animal model Marked A because it is an animal intervention or observation study measuring an organismal outcome (model: C. elegans); the code names the system studied -- animal work can be rigorous and still not be human data.
Study type	4 - Animal Study
Model system	C. elegans
Journal	Cell metabolism
Year	2012
Peer reviewed	Yes
Record last updated	2026-10-01
Source	DOI 10.1016/j.cmet.2012.04.007 · PMID 22560223 · Free full text (PMC3348514)

Extracted findings

These fields were extracted from the paper with AI assistance and have not been checked against the source. Read them as a pointer into the paper, not as curated claims; where they disagree with the curated summary above, the curated summary stands.

Intervention	Genetic + rapamycin (TORC1 inhibition)
Target	TORC1 / SKN-1(Nrf) / DAF-16(FoxO)
Model	C. elegans
Effect	Genetic TORC1 inhibition extends lifespan via SKN-1/Nrf and DAF-16/FoxO; rapamycin's effect needs SKN-1 but not DAF-16
Dose	not stated
Sample size	not stated
Effect size	not stated
Limitations	not stated

In the Atlas

Links in the pathway map

Supports mTORC1 inhibits Longevity
Supports FOXO1/3 activates Longevity

Cite this paper

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Robida-Stubbs, S., Glover-Cutter, K., Lamming, D. W., Mizunuma, M., Narasimhan, S. D., Neumann-Haefelin, E., Sabatini, D. M., & Blackwell, T. K. (2012). TOR signaling and rapamycin influence longevity by regulating SKN-1/Nrf and DAF-16/FoxO. Cell metabolism. https://doi.org/10.1016/j.cmet.2012.04.007

@article{ROB2012,
  author       = {Robida-Stubbs, S. and Glover-Cutter, K. and Lamming, D. W. and Mizunuma, M. and Narasimhan, S. D. and Neumann-Haefelin, E. and Sabatini, D. M. and Blackwell, T. K.},
  title        = {{TOR signaling and rapamycin influence longevity by regulating SKN-1/Nrf and DAF-16/FoxO}},
  journal      = {Cell metabolism},
  year         = {2012},
  doi          = {10.1016/j.cmet.2012.04.007},
  note         = {PMID: 22560223},
}

Cite this Atlas record

The record is the Atlas's own work — the evidence label, the extracted findings and the links. It is cited as part of the dataset, not as the paper.

Barton, O. (2026). Oliver's mTOR Atlas (record ROB2012) [Data set]. https://mtor-atlas.org/study/ROB2012/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_ROB2012,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record ROB2012},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/ROB2012/},
  doi          = {10.5281/zenodo.22059963}
}

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