mTOR

A protein kinase that senses nutrients and growth signals and decides whether a cell builds or recycles, and the target of the best validated lifespan extending drug in mammals.

What it does

mTOR is a kinase at the center of two complexes, mTORC1 and mTORC2. mTORC1 is the one people mean. It integrates amino acid availability, insulin and IGF-1 signaling, oxygen and cellular energy, then decides whether the cell should synthesize protein and grow or slow down and recycle.

When mTORC1 is active, protein synthesis rises and autophagy is suppressed. When it is inhibited, the reverse happens. This is the switch that connects eating patterns to cellular maintenance.

Why longevity research cares

Rapamycin inhibits mTORC1 and extended lifespan in genetically heterogeneous mice even when started in mid to late life, a result reproduced across laboratories through the Interventions Testing Program. Very few interventions have that track record.

Dietary protein restriction and caloric restriction reduce mTORC1 signaling as well, which is the mechanistic thread linking those diets to the same pathway.

The tradeoff nobody should skip

mTORC1 activation is also how muscle is built. Resistance training plus adequate protein works largely by activating this pathway. Chronically suppressing it in an adult trying to preserve muscle and bone into their seventies is not obviously wise, and the aging population most at risk is the one losing muscle, not gaining it.

There is no established protocol for mTOR inhibition in healthy humans for longevity, rapamycin is not approved for it, and the human trials that would settle the question are small and ongoing.

Baseline does not prescribe rapamycin or any mTOR inhibitor. This entry is here because the pathway explains most of the diet and fasting advice people encounter.

References

  1. Saxton RA, Sabatini DM. mTOR signaling in growth, metabolism, and disease. Cell. 2017.
  2. Harrison DE, et al. Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature. 2009.
  3. Miller RA, et al. Rapamycin-mediated lifespan increase in mice is dose and sex dependent. Aging Cell. 2014.