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.
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.
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.
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.
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.
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.
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) and for tuberous sclerosis complex.
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.
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.
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.
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.
A two-protein complex 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.
A genetic disorder caused by TSC1/TSC2 mutations that leaves mTORC1 stuck permanently active, 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.
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.
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.
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.
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.
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.
A small GTPase that directly activates mTORC1 at the lysosomal membrane once TSC1/TSC2's inhibitory brake is released. The final switch mTORC1's upstream signals converge on.
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.
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.
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.
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.
A reduced cellular response to insulin. Relevant to mTOR biology as rapamycin's best-documented metabolic side effect, mechanistically linked to chronic suppression of mTORC2 rather than mTORC1, its intended target.
Evidence tier (A–D)
This Atlas's own grading system for how directly a study supports a claim: A = systematic review/meta-analysis, B = human trial, C = animal model, D = mechanistic, in vitro, or review. Every study and every claim in the Atlas carries one of these tiers, visible as a colored badge next to its citation.
