Evidence that chronic inhibition of the mammalian Target of Rapamycin (mTOR) reduces skin blood flow in humans

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Chronic mTOR inhibition causes vascular dysfunction in rodents. We hypothesized that a similar effect would be observed in humans. 6 middle‐aged persons participated. mTOR was antagonized by topical application of 8% rapamycin (RAPA) ointment to skin. RAPA was applied twice daily for 7 days to an 8×8 cm area of skin on the abdomen while a second site was similarly treated with ointment vehicle only. We examined the effect of these treatments on skin blood flow (SkBF) as monitored by laser‐Doppler flowmetry (LDF). Local skin temperature (Tloc) was controlled with combined LDF/local heating probe holders. Tloc was maintained initially at 34°C and then was raised to 43°C to cause maximal local vasodilation (maxLDF).ResultsAt Tloc=34°C, SkBF was 72±4.3% maxLDF at RAPA treated sites and was 80±4.9% maxLDF at sites that received vehicle only (p<0.03 between sites). maxLDF (in mV) when Tloc was 43°C did not differ between RAPA and vehicle treated sites (p>;0.05). We conclude that chronic RAPA treatment reduces SkBF levels at normothermic skin temperatures in middle‐aged persons without an effect on maximal vasodilation. (supported by NIH Grant AG041365)