Rapamycin
weak data
The Dose Guy’s verdictOct 27, 20263 sources
Of everything sold as a longevity drug, rapamycin has the best case, and it is a mouse case. It extended lifespan in mice even when started late in life, at three separate labs, which nothing else on this shelf can say. In people the trials are small, short, and measure everything except whether you live longer, and at transplant doses it suppresses your immune system. If you want to run one longevity experiment on yourself, this is the defensible one: a weekly pulse, on a prescription, with bloodwork before and after. If you want the sure thing, it is still lifting, sleep, and staying lean.
What it is
Rapamycin came out of soil bacteria on Easter Island and became a transplant drug because it shuts down mTOR, the cell’s master growth switch. With mTOR on, cells build, divide, and grow. With it off, they shift into maintenance and clear out their own junk, a recycling process called autophagy. My read, and the bet behind the whole longevity scene: a lifetime of mTOR running hot is part of why we wear out, and turning it down is the most reproducible lifespan lever anyone has found in animals.
The catch is in the dosing. Hit mTOR hard every day, the transplant way, and you also blunt the immune system and push glucose and lipids the wrong way. The longevity crowd’s answer is the weekly pulse: one larger dose, then days for levels to fall away, the bet being that you get the housekeeping without the suppression. Next to metformin, the other prescription longevity bet, and NAD+, which has a real role in cellular energy but makes its case for older people and has little to show for a healthy young one, rapamycin is the one with the animal record to justify the experiment.
What the research shows
A strong animal story and a thin human one. The human trials so far tell you about safety and side effects at longevity doses, not about longevity:
Realistic protocols
The scene runs rapamycin as a once-weekly pulse, and that is the shape I would use. Most people land between 5 and 6 mg once a week. PEARL tested 5 and 10 mg of compounded rapamycin, so its milligrams line up with compounded capsules, not generic tablets. Start at 1 to 2 mg weekly for a few weeks to see how your mouth and gut take it, then step up if you tolerate it. The dose is not effect-driven the way a fat-loss drug is; you will not feel it working, so there is nothing to chase. Pick a dose your bloodwork tolerates and hold it. Some people run a bigger dose every two weeks instead, which spaces the exposure further apart for the same reason the weekly pulse exists.
Take it the same way every week, fed or fasted, because a fatty meal raises how much you absorb and you want each pulse to match the last. Compounded capsules and generic tablets also absorb differently, so a milligram on one is not a milligram on the other; switching means re-checking your labs. Grapefruit juice raises levels and some people use it on purpose. I would not, it turns your dose into a guess. The same goes for certain antibiotics and antifungals, so check any new prescription against rapamycin.
Get a lipid panel, fasting glucose or HbA1c, and a full blood count before you start and again six to eight weeks in. Skip the week if you are fighting an infection, and stop well ahead of surgery, because rapamycin slows wound healing. If you lift, the theory worry is that mTOR is the growth signal you train for. The weekly pulse leaves most of the week clear, and in PEARL the women on 10 mg gained lean mass rather than losing it.
Side effects
At a weekly pulse the side profile is mild, but rapamycin is still an immune drug and the labs are not optional:
