A new paper from Dudley Lamming’s group: (and I bet Brad Stanfield’s research in humans shows the same)… its all good news.
An increasing number of physically active adults are taking the mTOR inhibitor rapamycin off label with the goal of extending healthspan. However, frequent rapamycin dosing disrupts metabolic health during sedentary conditions and abates the anabolic response to exercise. Intermittent once-weekly rapamycin dosing minimizes many negative metabolic side effects of frequent rapamycin in sedentary mice. However, it remains unknown how different rapamycin dosing schedules impact metabolic, physical, and skeletal muscle adaptations to voluntary exercise training. Therefore, we tested the hypothesis that intermittent rapamycin (2 mg/kg; 1×/week) would avoid detrimental effects on adaptations to 8 weeks of progressive weighted wheel running (PoWeR) in adult female mice (5-month-old) by evading the sustained inhibitory effects on mTOR signaling by more frequent dosing schedules (2 mg/kg; 3×/week). PoWeR improved maximal exercise capacity, absolute grip strength, and myofiber hypertrophy with no differences between vehicle or rapamycin-treated mice despite greater voluntary running volume with intermittent rapamycin treatment. Conversely, frequent and intermittent rapamycin-treated mice had impaired glucose tolerance and insulin sensitivity compared to vehicle-treated mice after PoWeR; however, intermittent rapamycin reduced the impact on glucose intolerance versus frequent rapamycin. Collectively, these data in adult female mice suggest that (1) rapamycin is largely compatible with the physical and skeletal muscle benefits of PoWeR and (2) the detrimental effects of rapamycin on glucose metabolism in the context of voluntary exercise may be reduced by intermittent dosing.
Open Access Paper
https://onlinelibrary.wiley.com/doi/10.1111/acel.70183
13 Likes
Is once/week in mice comparable to once/week in humans? Since their metabolic rates are so much higher, I thought once/week for mice would be like once every several months in a human (but I hope that’s wrong!)
5 Likes
The dose is very high (2 mg/kg) and yes, mice metabolize much faster, about 4 times faster than people. I still think it is representative of the results we see in humans.
2 Likes
The once a week schedule in the mice is probably equivalent to once every 1-2 months in humans while the 3 times a week schedule would be equivalent to once every 1-3 weeks for humans.
2 Likes
