The UT Health trial using weekly dosing isn’t arbitrary. mTOR runs two jobs that are worth separating: cellular cleanup (autophagy, senescent cell clearance) and anabolic signaling (muscle protein synthesis). Inhibit it continuously and you suppress both indefinitely. Pulse weekly and you get deep inhibition during the window, then let anabolic recovery happen the other six days. For women on HRT trying to hold muscle through menopause, this distinction matters more than the longevity literature acknowledges. Rapamycin stacked with exogenous testosterone already has some mTOR interaction nobody’s studying carefully. Continuous daily dosing on top of that is a different experiment than weekly pulse. My working hypothesis: take it Monday, lift Tuesday through Thursday when mTOR is rebounding. That’s what I’ve been running since January at 2mg/week. Nothing alarming yet. Fasting glucose stable, lipids unchanged, CBC looks normal. The daily low-dose camp (1-2mg/day) cite more consistent autophagy. Maybe. But I lift heavy three days a week and I’m not interested in blunting MPS 365 days a year for marginally better cellular housekeeping. What I’m waiting for from the UT Health data: activity-level subgroup analysis. Whether you train seriously or don’t should change the interpretation entirely. That stratification would actually be worth reading.
the activity-level subgroup analysis is the part i keep circling back to as well. what i’d add as a caveat: training status shifts over a year, and a single baseline classification at enrollment will smear the signal. asking participants to log lifting frequency weekly would matter more than the intake form.
Logging frequency is the real ask here. “Single baseline classification will smear the signal” is exactly right, and it’s a bigger methodological problem than sample size in most of these trials. I’d push it further though: self-reported weekly logging has its own noise, especially in a population that may not have a consistent training definition. What counts as “lifting” for enrollment purposes? Three sets at the gym twice a week and someone running a linear progression four days a week are not the same mTOR environment. If UT Health wants subgroup analysis that’s actually interpretable, they need continuous load tracking, not frequency alone. Volume and intensity matter more than days per week for MPS signaling. I doubt the protocol captures any of that.
“continuous load tracking” sounds clean on paper but in my experience anything granular past week 8 has brutal dropout, even in motivated cohorts. asking for session RPE plus weekly set count tends to outlast asking for tonnage, because that’s what people actually remember to log. the volume/intensity point stands either way, that part i agree with. whether an IRB even lets them collect activity data that detailed is its own question. ymmv.