mTOR regulates the pro-tumorigenic senescence-associated secretory phenotype by promoting IL1A translation

Laberge RM, Sun Y, Orjalo AV, Patil CK, Freund A, Zhou L, Curran SC, Davalos AR, Wilson-Edell KA, Liu S, Limbad C, …, Campisi J · 2015 · Nature Cell Biology · Atlas ID LAB2015

What this study shows

Explained HOW rapamycin calms 'inflammaging'. Senescent cells spew inflammatory signals (the SASP) that damage surrounding tissue and even feed tumors. mTOR powers this by translating IL1A, the cytokine at the top of the cascade. Rapamycin selectively shuts it down - and blocked senescent cells from fueling prostate tumor growth in mice.

Abstract

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The TOR (target of rapamycin) kinase limits longevity by poorly understood mechanisms. Rapamycin suppresses the mammalian TORC1 complex, which regulates translation, and extends lifespan in diverse species, including mice. We show that rapamycin selectively blunts the pro-inflammatory phenotype of senescent cells. Cellular senescence suppresses cancer by preventing cell proliferation. However, as senescent cells accumulate with age, the senescence-associated secretory phenotype (SASP) can disrupt tissues and contribute to age-related pathologies, including cancer.

Read the full abstract on PubMed →

At a glance

Evidence type	M Molecular — cells, biochemistry, structure Marked M because it is molecular or in-vitro work (model: Human cells + mouse xenografts) 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 cells + mouse xenografts
Journal	Nature Cell Biology
Year	2015
Peer reviewed	Yes
Record last updated	2026-10-01
Source	DOI 10.1038/ncb3195 · PMID 26147250 · Free full text (PMC4691706)

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	Rapamycin (mTORC1 inhibition)
Target	mTORC1 / IL1A / SASP
Model	Human cells + mouse xenografts
Effect	Rapamycin blunts the pro-tumorigenic senescence-associated secretory phenotype by suppressing IL1A translation

In the Atlas

Links in the pathway map

Supports mTORC1 activates Senescence-associated secretory phenotype (SASP)

Open questions that cite this study

Cited as supporting evidence for the open question How much of rapamycin's healthspan benefit runs through fewer senescent cells?.

Cite this paper

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Laberge, R. M., Sun, Y., Orjalo, A. V., Patil, C. K., Freund, A., Zhou, L., Curran, S. C., Davalos, A. R., Wilson-Edell, K. A., Liu, S., Limbad, C., Demaria, M., Li, P., Hubbard, G. B., Ikeno, Y., Javors, M., Desprez, P. Y., Benz, C. C., Kapahi, P., Nelson, P. S., & Campisi, J. (2015). mTOR regulates the pro-tumorigenic senescence-associated secretory phenotype by promoting IL1A translation. Nature Cell Biology. https://doi.org/10.1038/ncb3195

@article{LAB2015,
  author       = {Laberge, R. M. and Sun, Y. and Orjalo, A. V. and Patil, C. K. and Freund, A. and Zhou, L. and Curran, S. C. and Davalos, A. R. and Wilson-Edell, K. A. and Liu, S. and Limbad, C. and Demaria, M. and Li, P. and Hubbard, G. B. and Ikeno, Y. and Javors, M. and Desprez, P. Y. and Benz, C. C. and Kapahi, P. and Nelson, P. S. and Campisi, J.},
  title        = {{mTOR regulates the pro-tumorigenic senescence-associated secretory phenotype by promoting IL1A translation}},
  journal      = {Nature Cell Biology},
  year         = {2015},
  doi          = {10.1038/ncb3195},
  note         = {PMID: 26147250},
}

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 LAB2015) [Data set]. https://mtor-atlas.org/study/LAB2015/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_LAB2015,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record LAB2015},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/LAB2015/},
  doi          = {10.5281/zenodo.22059963}
}

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