Persistent mTORC1 signaling in cell senescence results from defects in amino acid and growth factor sensing

Carroll B, Nelson G, Rabanal-Ruiz Y, Kucheryavenko O, Dunhill-Turner NA, Chesterman CC, Zahari Q, Zhang T, Conduit SE, Mitchell CA, Maddocks ODK, Lovat P · 2017 · The Journal of cell biology · Atlas ID CAR2017

What this study shows

Explains why mTORC1 stays switched on in senescent cells. In human fibroblasts rendered senescent three different ways, mTORC1 is constitutively active and no longer responds to serum or amino acid withdrawal. The defect is upstream, not in mTORC1 itself: it is driven in part by depolarisation of the senescent plasma membrane, which leads to primary cilia defects and a failure to shut off growth-factor signalling, while increased autophagy and high intracellular amino acid levels may act to support the nutrient arm. Correcting these inputs restored sensitivity of the pathway and killed the cells, which frames persistent mTORC1 signalling as a survival dependency of senescent cells rather than a by-product of senescence.

Abstract

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Mammalian target of rapamycin complex 1 (mTORC1) and cell senescence are intimately linked to each other and to organismal aging. Inhibition of mTORC1 is the best-known intervention to extend lifespan, and recent evidence suggests that clearance of senescent cells can also improve health and lifespan. Enhanced mTORC1 activity drives characteristic phenotypes of senescence, although the underlying mechanisms responsible for increased activity are not well understood.

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At a glance

Evidence type	M Molecular — cells, biochemistry, structure Marked M because it is molecular or in-vitro work (model: Human fibroblasts made senescent by stress, replicative exhaustion or oncogene activation) rather than a whole-organism health-outcome study. That is often exactly where causal biology gets established -- the code says which system the finding was shown in, and nothing about how good the work is.
Study type	5 - Mechanistic / In Vitro
Model system	Human fibroblasts made senescent by stress, replicative exhaustion or oncogene activation
Journal	The Journal of cell biology
Year	2017
Peer reviewed	Yes
Record last updated	2026-09-23
Source	DOI 10.1083/jcb.201610113 · PMID 28566325

Cite this paper

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Carroll, B., Nelson, G., Rabanal-Ruiz, Y., Kucheryavenko, O., Dunhill-Turner, N. A., Chesterman, C. C., Zahari, Q., Zhang, T., Conduit, S. E., Mitchell, C. A., Maddocks, O. D. K., Lovat, P., von Zglinicki, T., & Korolchuk, V. I. (2017). Persistent mTORC1 signaling in cell senescence results from defects in amino acid and growth factor sensing. The Journal of cell biology. https://doi.org/10.1083/jcb.201610113

@article{CAR2017,
  author       = {Carroll, B. and Nelson, G. and Rabanal-Ruiz, Y. and Kucheryavenko, O. and Dunhill-Turner, N. A. and Chesterman, C. C. and Zahari, Q. and Zhang, T. and Conduit, S. E. and Mitchell, C. A. and Maddocks, O. D. K. and Lovat, P. and von Zglinicki, T. and Korolchuk, V. I.},
  title        = {{Persistent mTORC1 signaling in cell senescence results from defects in amino acid and growth factor sensing}},
  journal      = {The Journal of cell biology},
  year         = {2017},
  doi          = {10.1083/jcb.201610113},
  note         = {PMID: 28566325},
}

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 CAR2017) [Data set]. https://mtor-atlas.org/study/CAR2017/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_CAR2017,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record CAR2017},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/CAR2017/},
  doi          = {10.5281/zenodo.22059963}
}