Glossary of mTOR terms

25 core terms for understanding mTOR biology – from the two mTOR complexes themselves down to the individual genes, drugs, and processes that make up the pathway. Each term links to its full evidence page in the Atlas where one exists.

mTOR (108 studies in the Atlas)

Mechanistic target of rapamycin. A serine/threonine kinase that acts as a cell's central growth-vs-conservation switch, integrating nutrient availability, growth factor signals, and energy status. Forms two distinct complexes, mTORC1 and mTORC2.

mTORC1 (177 studies in the Atlas)

mTOR Complex 1. Regulates protein synthesis, autophagy, and cell growth in response to nutrients and growth factors. This is the complex rapamycin directly and potently inhibits.

mTORC2 (36 studies in the Atlas)

mTOR Complex 2. Phosphorylates Akt/PKB and affects cell survival and glucose metabolism. Not directly blocked by rapamycin – only reached indirectly, with chronic dosing, which is the likely source of rapamycin's insulin-resistance side effect.

Rapamycin (Sirolimus) (79 studies in the Atlas)

The founding mTOR inhibitor, first isolated in 1975 from a soil bacterium on Rapa Nui (Easter Island). Binds the protein FKBP12 and allosterically blocks mTORC1. The most consistently lifespan-extending drug in laboratory animal studies.

Rapalog

Any chemical analog of rapamycin engineered from the same core structure – everolimus, temsirolimus, and ridaforolimus are the main examples. All share rapamycin's FKBP12-dependent, mTORC1-selective mechanism.

Everolimus (21 studies in the Atlas)

A semi-synthetic rapalog with better oral bioavailability and a shorter half-life than rapamycin itself. Used clinically in oncology (breast cancer, pancreatic neuroendocrine tumors, kidney cancer), for tuberous sclerosis complex, and to prevent organ-transplant rejection (as Zortress).

Metformin (6 studies in the Atlas)

A widely used antidiabetic drug that activates AMPK and inhibits mTORC1 indirectly — though part of its action bypasses AMPK entirely. Frequently proposed as a geroprotector candidate alongside rapamycin, with a weaker evidence base in this Atlas.

Resveratrol (3 studies in the Atlas)

A plant polyphenol popularized as a sirtuin activator and "calorie-restriction mimetic." Failed to extend lifespan in the Interventions Testing Program's mouse studies and showed no metabolic benefit in a human RCT.

Autophagy (44 studies in the Atlas)

The cell's internal recycling process – breaking down and reusing damaged proteins and organelles. Suppressed by active mTORC1 and switched on when mTORC1 is inhibited. Widely proposed, but not proven, as the mechanism behind rapamycin's lifespan benefit.

Cellular senescence (16 studies in the Atlas)

A state in which a cell permanently stops dividing but stays alive, secreting inflammatory signals (the SASP). Senescent cells accumulate with age and drive age-related disease; mTOR both promotes the senescent state and powers its inflammatory secretions.

TSC1/TSC2

A protein complex (TSC1, TSC2 and TBC1D7) that acts as the principal brake on mTORC1, integrating signals about cellular stress and growth-factor availability. Loss-of-function mutations in either gene cause tuberous sclerosis complex.

Tuberous sclerosis complex (11 studies in the Atlas)

A genetic disorder caused by TSC1/TSC2 mutations that leaves mTORC1 active without its growth-factor brake (nutrients still gate it), causing benign tumors in the brain, kidney, and elsewhere. The clearest human proof-of-concept that mTOR hyperactivation alone can drive tumor growth – and that mTOR inhibitors (everolimus) can treat it directly.

AMPK

AMP-activated protein kinase – a cellular energy sensor that activates when ATP runs low. Inhibits mTORC1 upstream, making it mTOR's functional opposite in the growth-vs-conservation decision. The main (though not sole) route by which metformin affects mTORC1.

Akt/PKB

A kinase downstream of growth-factor signaling (via PI3K) that activates mTORC1 and is itself phosphorylated by mTORC2 – placing it at a hinge point between the pathway's two complexes.

4E-BP1

A direct mTORC1 substrate that, when phosphorylated, releases the translation initiation factor eIF4E to start protein synthesis. Notable as one of the mTORC1 substrates rapamycin blocks incompletely – a gap that motivated newer, more potent ATP-competitive and bi-steric mTOR inhibitors.

S6K1

p70 S6 kinase – one of the first mTORC1 substrates identified, back when the pathway itself was still unnamed. Promotes protein synthesis and cell growth downstream of active mTORC1.

Raptor

Regulatory-associated protein of mTOR – the defining scaffold subunit of mTORC1, which presents substrates such as S6K1 and 4E-BP1 to the kinase. In mTORC1 the FRB site where FKBP12-rapamycin docks stays exposed, so this is the complex rapamycin blocks directly.

Rictor

Rapamycin-insensitive companion of mTOR – the defining scaffold subunit of mTORC2, and the reason mTORC2 isn't directly blocked by rapamycin the way mTORC1 is.

Rheb

A small GTPase that directly activates mTORC1 once TSC1/TSC2's inhibitory brake is released – the step the growth-factor inputs converge on. Which membrane the activating pool sits on is not settled; the Atlas records that as an open question rather than asserting the lysosome.

Rag GTPases

A family of GTPases that recruit mTORC1 to the lysosomal surface in response to amino acid availability – the mechanism by which mTORC1 senses nutrients, independent of growth-factor signaling through Rheb.

TFEB

A transcription factor that drives expression of autophagy and lysosomal genes. Normally kept inactive by mTORC1-dependent phosphorylation; when mTORC1 is inhibited, TFEB moves to the nucleus and switches on the cell's recycling program.

Lysosome

The cell's main digestive/recycling organelle, and the physical platform where mTORC1 is activated (via the Rag GTPases and Ragulator complex) and where autophagy's breakdown products are processed.

Caloric restriction

Sustained reduction in calorie intake without malnutrition – the original, best-replicated lifespan-extending intervention across species, and one that lowers mTORC1 activity through multiple converging nutrient- and energy-sensing pathways.

Insulin resistance

A reduced cellular response to insulin. Relevant to mTOR biology as rapamycin's best-documented metabolic side effect, linked mainly to chronic suppression of mTORC2 in mice (LAM2012); how much of the effect in people comes from mTORC2 loss and how much from other routes has not been separated.

Evidence code (S/H/A/M/R)

This Atlas's label for WHICH SYSTEM a finding was established in — never a mark for how good the work is: S = synthesis of human data, H = human study, A = animal model, M = molecular (cells, biochemistry, structure), R = review. Every study and claim carries one, visible as a badge next to its citation. Two outlined markers sit beside these: PP, a preprint not yet peer-reviewed, and RT, a registered trial with no results yet. They say how complete the record is, not which system a finding comes from. Until September 2026 these codes ran A–D; they were renamed because a lettered ladder reads as a school grade whatever the caption says.

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