Pathway link MTORC1-LONGEVITY
mTORC1 Longevity
mTORC1 inhibits Longevity.
Turning mTORC1 down extends lifespan in yeast, worms, flies and mice – one of the best-replicated anti-ageing effects in laboratory animals. In mice, how big the effect is depends on sex, strain, diet and when treatment starts, and it has not been shown in people.
The conditions it holds under
No human hard-endpoint evidence. This is the Atlas's flagged 'human endpoint desert'.
Strongly modified by sex, strain, diet and the age at which inhibition starts. Effect direction is reproducible; effect size is not transferable between models.
- Time it takes
- long exposure (days to weeks)
- Step
- indirect (through steps not drawn here)
- Measured in
- multiple species
- Reaches people?
- not tested in people
- How settled
- settled in the literature
Studies behind it
| Year | Evidence | Study |
|---|---|---|
| 2009 | A | Rapamycin fed late in life extends lifespan in genetically heterogeneous miceHAR2009 Rapamycin fed from 600 days of age extended median and maximal lifespan in both sexes; age at 90% mortality rose 14% in females and 9% in males. |
| 2012 | A | Rapamycin-induced insulin resistance is mediated by mTORC2 loss and uncoupled from longevityLAM2012 Chronic rapamycin (about 2 mg/kg a day, close to the lifespan-extending dose) made mice glucose intolerant and insulin resistant. A clamp test placed the problem in the liver, which kept making glucose, while muscle and fat took up glucose normally. Removing mTORC1 from the liver did not cause this. Rapamycin did break up mTORC2 (it separated mTOR from Rictor) in liver, fat and muscle, and deleting Rictor in the liver alone reproduced the glucose problem. In the genetic part, female mice with one working copy each of mTOR and mLST8 had about 50% less mTORC1 signalling in the liver, normal mTORC2 signalling and normal glucose tolerance, and lived 14.4% longer on average (p = 0.046). Males did not. Boundary: mouse drug and genetics work, not people, and the lifespan gain is female-only. It supports separating the two effects, but the paper does not test a drug that blocks mTORC1 without touching mTORC2. |
| 2012 | A | TOR signaling and rapamycin influence longevity by regulating SKN-1/Nrf and DAF-16/FoxOROB2012 In C. elegans, genetic TORC1 inhibition extends lifespan through SKN-1/Nrf and DAF-16/FoxO, whereas rapamycin's lifespan effect requires SKN-1 but not DAF-16, apparently because it also hits TORC2. |
| 2003 | A | Genetics: influence of TOR kinase on lifespan in C. elegansVEL2003 Silencing the single worm TOR gene roughly doubled C. elegans lifespan, showing the longevity role of TOR inhibition is conserved across an enormous evolutionary distance. |
| 2008 | A | A role for autophagy in the extension of lifespan by dietary restriction in C. elegansHAN2008 Makes autophagy a necessary step between dietary restriction and a longer life, not a side effect of it: blocking autophagy genes abolishes the lifespan extension produced both by dietary restriction and by TOR inhibition. The paper is equally careful about what autophagy cannot do on its own, because autophagy still runs in animals lacking DAF-16/FOXO and yet those animals are not long-lived. Boundary: worms; necessity was shown, sufficiency was not. |
| 2006 | M | Extension of chronological life span in yeast by decreased TOR pathway signalingPOW2006 Decreased TOR pathway signalling extends chronological lifespan in yeast. |
| 2026 | A | Lsp2 links mTORC1 to TOP mRNA translation and lifespan in DrosophilaWAN2026 Identifies Lsp2, a Drosophila fat-body storage protein, as an amino-acid-induced feedback activator of mTORC1 that specifically boosts translation of TOP-motif mRNAs (mostly ribosomal proteins) via 4E-BP — a rapamycin-resistant arm of mTORC1 output. Genetic loss of Lsp2 reduces TOP mRNA translation and robustly extends lifespan without cost to reproduction, revealing a rapamycin-independent route from mTORC1 activity to organismal longevity. |
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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