Pathway link CR-MTORC1

Fasting / caloric restriction ⊣ mTORC1

Fasting / caloric restriction inhibits mTORC1.

Eating less is expected to turn mTORC1 down, because the cell's fuel and amino-acid sensors both report scarcity. But this has not been measured here. The one study behind this arrow let mice eat freely on 25 different diets and found that the ratio of protein to carbohydrate, not the number of calories, went with health and lifespan, and lower-protein diets went with lower mTOR activity in the liver. So what has support is eating less protein, not eating less, and it is a correlation, not a test.

Reduced nutrient and energy availability is expected to lower mTORC1 through the amino-acid and energy arms at once - the sensors detect scarcity and AMPK detects the falling energy charge. Note what supports that expectation here, because it is less than the claim's reputation suggests. No study in this corpus measures mTORC1 under fasting or energy restriction. The single supporting study, SOL2014, fed mice ad libitum across 25 diets and concluded that the macronutrient RATIO, not caloric intake, set lifespan and cardiometabolic health; the mTOR link in it is a correlation between a lower protein-to-carbohydrate ratio and lower hepatic mTOR activation. So the supported variable is dietary protein, not calories, and the measurement is associative rather than interventional.

The conditions it holds under

Supporting evidence is thinner than the claim's reputation. ROM2016 (two-year caloric restriction is tolerable in non-obese humans) and MAT2017 (rhesus survival) were removed as support in the 2026-09-21 audit because neither measured mTORC1; they belong to the CR-LONGEVITY edge. That leaves SOL2014, which is an ad-libitum 25-diet study whose own title states that the ratio of macronutrients, not caloric intake, dictates the outcome, and whose mTOR observation is correlative and confined to liver. Re-audit 2026-10-10: consensus was downgraded from established to emerging and the evidence kind from genetic epistasis to correlative, because neither matched what SOL2014 actually did. The edge is retained because the mechanistic expectation is sound and well motivated by the sensor arms, but it is an expectation, not a measured result in this corpus. 2026-10-18: YIL2012 added. In mouse intestine, calorie restriction lowered mTORC1 activity in Paneth cells, and rapamycin or Paneth-cell genetics reproduced the stem-cell effect, so the corpus now has one direct mTORC1 measurement under restriction. It is a single tissue in mice and does not show the same in people.

Time it takes

long exposure (days to weeks)

Step

indirect (through steps not drawn here)

Measured in

mouse

Where in the cell

lysosome

Reaches people?

plausible in people, not shown directly

How settled

emerging, few independent studies

Studies behind it

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.

“Inhibits” describes the effect on the target's activity, not on how much of it there is.

“How settled” describes how far researchers in the field agree. It is not the same as the sign-off above, which only says whether a named curator has checked this page.

If this link rests on your own work: a click on “This looks right” below, or a short note through “Report an error”, helps us more than anything else on this page.

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