Oliver's mTOR Atlas Evidence Platform
Reading level
Mode

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, …, Korolchuk VI · 2017 · 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

ShowHide

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.

Read the full abstract on PubMed →

At a glance

ShowHide
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 type5 - Mechanistic / In Vitro
Model systemHuman fibroblasts made senescent by stress, replicative exhaustion or oncogene activation
JournalJournal of Cell Biology
Year2017
Peer reviewedYes
Record last updated2026-10-01
SourceDOI 10.1083/jcb.201610113 · PMID 28566325

Where this study fits

How this study connects to the pathway map, open questions, people and other studies in the Atlas.

People in the Atlas

  • Bernadette Carroll first author · 3 studies in the Atlas

    First author of the study showing why mTORC1 stays switched on in senescent cells, and co-author on G3BP–TSC and senescence-mitophagy work; her own lab studies how nutrient sensing breaks down in ageing cells.

  • Viktor I. Korolchuk last author · 5 studies in the Atlas

    Showed that where lysosomes sit inside the cell tunes mTORC1 activity to nutrient supply. His Newcastle lab found that senescent cells can no longer switch mTORC1 off when nutrients or growth factors are withdrawn, and studies how autophagy and mitophagy decline with age

  • Glyn Nelson 2 studies in the Atlas

    Microscopy specialist who manages Newcastle University's Bioimaging Unit and has worked for many years on the signalling networks that keep senescent cells in their arrested state

  • Penny Lovat 2 studies in the Atlas

    Professor of Cellular Dermatology and Oncology at Newcastle University who studies autophagy in melanoma, and whose work on the autophagy protein AMBRA1 and the skin protein loricrin underlies a test, developed with AMLo Biosciences, to identify early melanomas at low risk of spreading

  • Thomas von Zglinicki 2 studies in the Atlas

    Cell-senescence researcher who co-authored the Newcastle studies on stuck-on mTORC1 in senescent cells and on loss of basal mitophagy as a driver of cellular ageing.

More: 9 other authors

No profile yet: Rabanal-Ruiz Y, Kucheryavenko O, Dunhill-Turner NA, Chesterman CC, Zahari Q, Zhang T, Conduit SE, Mitchell CA, Maddocks ODK

Related studies

More related studies

All 212 studies on mTORC1

Topics

Cellular senescencemTORC1

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.

InterventionSenescence induction (oxidative stress, replicative exhaustion, oncogene activation); serum and amino-acid starvation; correction of membrane depolarisation and cilia defects
TargetmTORC1 growth-factor and amino-acid sensing inputs
ModelHuman fibroblasts
EffectSenescent human fibroblasts keep mTORC1 constitutively active and starvation-resistant, and restoring pathway sensitivity killed the cells, suggesting persistent mTORC1 signalling supports senescent-cell survival.

Cite this paper

ShowHide 
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. 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      = {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}
}
Was this page useful?