Pathway link MTORC1-SENESCENCE
mTORC1 Senescence-associated secretory phenotype (SASP)
mTORC1 activates Senescence-associated secretory phenotype (SASP).
mTORC1 keeps old, "senescent" cells pumping out inflammatory signals, and blocking it calms that output down without making those cells young again. Whether mTORC1 also helps push cells into senescence in the first place is a separate question this arrow does not answer.
The conditions it holds under
Three studies, all in cells or a rat disease model. LAB2015 and NAR2011 measure the secretory output of cells that are already senescent (IL1A translation; IL-6/IL-8 production fuelled by mTOR at the TASCC). CHEN2026C (human disc cells, rat needle-puncture model) shows mTORC1 hyperactivation after TSC2 loss together with senescence and SASP, both blocked by rapamycin - a disease-model result, not a general demonstration that mTORC1 drives cells into senescence. That is why this arrow lands on the secretory programme and not on senescence itself.
- Time it takes
- days
- Step
- indirect (through steps not drawn here)
- Measured in
- mammalian cells
- Reaches people?
- plausible in people, not shown directly
- How settled
- emerging, few independent studies
Studies behind it
| Year | Evidence | Study |
|---|---|---|
| 2015 | M | mTOR regulates the pro-tumorigenic senescence-associated secretory phenotype by promoting IL1A translationLAB2015 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. |
| 2026 | A | Impaired Chaperone-Mediated Autophagy Accelerates Intervertebral Disc Degeneration by Inducing MIDN Accumulation to Target TSC2 for Proteasomal DegradationCHEN2026C Loss of chaperone-mediated autophagy lets its substrate midnolin (MIDN) accumulate; MIDN binds TSC2 and drives its proteasomal degradation independently of ubiquitination, de-repressing mTORC1 and causing senescence, SASP and matrix loss in disc cells. MIDN knockdown, LAMP2A overexpression or rapamycin each blocked the degeneration - a new upstream route to mTORC1 hyperactivation. |
| 2011 | M | Spatial coupling of mTOR and autophagy augments secretory phenotypesNAR2011 Protein synthesis and autophagic degradation are usually described as opposites that mTOR switches between, and this paper shows a compartment where the cell deliberately runs both at once. In senescent cells, autolysosomes and mTOR gather at one side of the Golgi (the TASCC), mTOR gets there in an amino-acid- and Rag-dependent way, and destroying that arrangement cuts interleukin-6/8 secretion. Boundary: cells, not organisms; it explains how the senescent secretory programme is fuelled, not whether blocking it helps an animal. |
Points the other way
No study in the Atlas contradicts this link. That means none in this curated set, not none in the literature.
Who has checked this
- Checked by
- No researcher outside the project has checked this link yet.
- Curator sign-off
- Not signed off yet. This link was drafted with AI help and has not been reviewed link by link; treat it as a proposal until it is.
- Curated by
- Oliver Barton, with AI help for drafting; see how links are checked.
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