Senescence-associated secretory phenotype (SASP)
Inflammatory secretory programme of senescent cells, supported translationally by mTORC1.
The inflammatory signals that senescent cells pump out. The inflammatory signals that senescent cells pump out.
Drawn as its own node because the evidence is about the secretome, not about becoming senescent: LAB2015 shows mTORC1 promoting IL1A translation in cells that are already arrested, and rapamycin suppressing the secretome while the arrest stays.
TL;DR. Senescence-associated secretory phenotype (SASP) appears in 4 curated studies in Oliver's mTOR Atlas: 1 in people (1 synthesis of human data); 1 in animal models; 2 at the molecular level (cells, biochemistry, structure). It has 1 interaction in the curated pathway model.
In the pathway model
| Interaction | Mechanism | Evidence | Studies |
|---|---|---|---|
| mTORC1 activates Senescence-associated secretory phenotype (SASP) mechanism: functional-consequence · this link in full · on the map table | 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. mTORC1 sustains the inflammatory secretory output of cells that are already senescent, by promoting IL1A translation. Inhibiting it quietens that output without reversing the proliferative arrest. mTORC1 sustains the inflammatory secretory output of cells that are already senescent, by promoting IL1A translation. Inhibiting it quietens that output without reversing the proliferative arrest. 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. plausible in people, not shown directly · emerging, few independent studies | A | LAB2015, CHEN2026C, NAR2011 |
Evidence at a glance
| Evidence | What it means | Studies |
|---|---|---|
| S | Synthesis of human data | 1 |
| A | Animal model | 1 |
| M | Molecular — cells, biochemistry, structure | 2 |
Studies
| Year | Evidence | Study |
|---|---|---|
| 2026 | S | Therapeutic reversal of cellular senescence: A systematic review of senolytics, senomorphics and anti-ageing therapies in human clinical trials TRI2026 A PRISMA-guided systematic review of six completed human clinical studies that met its eligibility criteria, testing drugs that clear or calm senescent ("zombie") cells -- senolytics such as dasatinib+quercetin, plus senomorphic and mTOR-targeting approaches. It reported limited and heterogeneous results, a mixture of biomarker and functional outcomes, with mostly mild side effects, and judged the evidence too thin (small samples, short follow-up) to call any of it an established therapy yet. Six INCLUDED studies is not a census of every completed human senotherapeutic trial: inclusion depends on the review's search date and eligibility criteria, and those have to be stated before any field-wide coverage conclusion is drawn. Useful mainly as a rare systematic look at where human senescence-targeting trials, mTOR inhibitors included, stand -- not as proof that any one drug works. |
| 2026 | A | Impaired Chaperone-Mediated Autophagy Accelerates Intervertebral Disc Degeneration by Inducing MIDN Accumulation to Target TSC2 for Proteasomal Degradation CHEN2026C 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. |
| 2015 | M | mTOR regulates the pro-tumorigenic senescence-associated secretory phenotype by promoting IL1A translation LAB2015 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. |
| 2011 | M | Spatial coupling of mTOR and autophagy augments secretory phenotypes NAR2011 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. |
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