Dietary rapamycin selectively improves arterial function in old mice

Dietary mTOR(definition)-inhibiting drug studied for extending healthspan and lifespan." style="text-decoration:underline dotted; text-underline-offset:2px; cursor:help;">rapamycin(definition) inhibits mTOR, reduces age‐related pathologies and extends lifespan, but it is unknown if it can reverse age‐related arterial dysfunction. The effects of mTOR inhibition on endothelial function and arterial stiffness were evaluated in young (Y: 6±2 mo) and old (O: 30±2 mo) male B6D2F1 mice fed control (C) or rapamycin‐supplemented (RAP: 14mg/kg encapsulated chow) diet ad libitum (6 wk). Aortic mTOR signaling, assessed by Western blot, was higher in aged mice (1.0±0.5 v. 2.59±0.8 AU, P<0.05) and lower in rapamycin‐treated old mice (1.5±0.3 AU, P<0.05). Rapamycin selectively increased NO bioavailability (OC v. ORAP, P<0.05) and augmented endothelium‐dependent dilation to acetylcholine (YC: 96±2% v. OC: 73±4%, P<0.05; v. ORAP: 95±1%, P<0.05) in carotid arteries of old mice. RAP also reduced aortic stiffness, assessed by pulse wave velocity, in old animals (Post‐Pre: −43±19 cm/s, P<0.05). These improvements coincided with lower aortic nitrotryosine (YC: 1.0±0.2 v. OC: 4.7 ±1.6, P<0.05; v ORAP: 1.5±0.3, P<0.05) and collagen expression (YC: 37±9% v. OC: 78±5%, P<0.05; v. ORAP: 50±9%, P<0.05). In young mice, RAP impaired endothelial function (P<0.05) and did not affect arterial stiffness. In conclusion, rapamycin improves arterial function in old mice with enhanced mTOR activity, suggesting that mTOR may be an effective therapeutic target in older adults.