Rapamycin is the most studied longevity drug on Earth and the one almost nobody is taking. Bryan Johnson stopped his protocol because his biological-age numbers got worse. Peter Attia takes it weekly and tells anyone who’ll listen that it’s the single best longevity intervention in his protocol. The rest of the longevity space is somewhere between those two poles, arguing about dose, frequency, and whether your immune system is going to fall apart.
I’ve been running rapamycin for two years. I’m 47. I lift heavy, train almost every day, run TRT, and have spent the last decade testing every longevity intervention worth running. Rapamycin is the one I would not give up. Here’s the protocol, the bloodwork, what to track, and the side effects I actually got — not the side effects the internet is afraid of.
What Rapamycin Actually Does
Rapamycin (sirolimus) is a macrolide originally isolated from a soil bacterium on Easter Island — Rapa Nui, hence the name. The pharmaceutical world figured out it inhibits a protein called mTOR (mechanistic target of rapamycin). mTOR is the master switch for cell growth and protein synthesis. When mTOR is on, cells grow. When mTOR is suppressed, cells switch into autophagy — the cellular cleanup process that recycles damaged organelles and misfolded proteins.
Aging is — at the cellular level — partly a story of too much mTOR signaling and not enough autophagy. Cells keep growing, accumulate damage, and stop cleaning themselves up. Rapamycin is the only known pharmaceutical that hits this directly.
The mouse data is staggering: rapamycin extends lifespan in middle-aged mice by 9–14% even when started in late life. No other compound has ever produced that result this consistently across labs. The dog data (the Dog Aging Project) is showing similar trends. The human data — full mortality endpoints — won’t exist for another decade because nobody runs 30-year RCTs on healthy people. But the mechanistic data, the biomarker data, and the biological-age clock data in humans are all pointing the same direction.
The Lifter’s Problem With Rapamycin
If mTOR is the protein synthesis switch, and lifting weights flips that switch on as hard as possible, then suppressing mTOR with rapamycin should — in theory — wreck muscle growth. This is the legitimate concern every serious lifter has about rapamycin and it’s why most bodybuilders won’t touch it.
The reality is more nuanced. Rapamycin at low weekly pulse doses is selective for mTORC1, less for mTORC2 — and the muscle hypertrophy story involves both. Continuous daily rapamycin (the transplant dose) does suppress hypertrophy. Once-weekly pulsing at 5–8 mg in a healthy adult appears to mostly preserve muscle while still hitting the autophagy and longevity benefits. “Appears to” because the human dataset is small.
What I’ve actually seen in two years on rapamycin: lean mass per DEXA went from 184 lbs to 187 lbs over 24 months, training the same. Strength on every major lift held or increased. I’m not winning any IFBB shows, but I’m not losing muscle either. If anything, the recovery is better.
My Rapamycin Protocol
Dose: 6 mg, once weekly, taken on Saturday morning fasted with a small amount of grapefruit juice (CYP3A4 inhibition increases rapamycin bioavailability roughly 3-fold — I started at 2 mg with grapefruit, which is the equivalent of about 6 mg without it).
Why Saturday: The biggest concern with rapamycin is impaired wound healing and slightly elevated infection risk for 24–48 hours post-dose. I take it Saturday morning, do mobility work that day instead of heavy lifting, and by Monday I’m back at full intensity. If I’m fighting a cold or have any open injury, I skip the dose.
Why fasted: Rapamycin absorption is more reliable on an empty stomach. The grapefruit juice trick is consistent — I’ve been doing the same 4 oz at the same time of day for two years.
Cycling: 12 weeks on, 4 weeks off. The off weeks are insurance against any chronic mTORC2 suppression and a chance to redo bloodwork in a clean state.
What I avoid pairing it with: Statins on the same day (CYP3A4 competition), other CYP3A4-heavy drugs, and absolutely no live vaccines while on protocol.
Bloodwork — What to Track
Rapamycin can move several markers. The serious ones to monitor:
- Lipids — especially triglycerides and LDL. This is the single most common side effect in the human data. Some people see triglycerides spike 20–40%. Mine went from 88 to 102 in the first 90 days, then settled at 95. Manageable.
- Fasting glucose and HbA1c. Rapamycin can cause a transient insulin resistance bump, especially at higher or daily doses. Mine moved from 5.1 to 5.4 HbA1c, no change at the weekly pulse dose.
- CBC with differential. Watch for any lymphocyte or platelet drops. Mine never moved.
- Comprehensive metabolic panel. Liver and kidney markers — both have stayed boring on my protocol.
- hsCRP. Mine dropped — from 1.2 to 0.4 at the 6-month mark. Inflammation came down, which lines up with the mechanism.
- IGF-1. Track because the longevity argument depends on knowing whether you’re hitting the lower-IGF-1 lane (longevity) or fighting it with too many GH peptides (growth).
If you’re already on serious GH peptides like CJC-1295 / Ipamorelin, you’re pushing IGF-1 up while rapamycin is pushing autophagy up. They aren’t opposed — they’re working different timeframes — but the bloodwork gets interesting and you need to know what you’re looking at.
Side Effects I Actually Got
Two years, every dose tracked. The honest list:
- Mouth sores — 3 episodes total, each lasted about 4 days, each resolved on its own. This is the classic rapamycin side effect. Lower the dose for the next cycle if you get them repeatedly.
- One bout of slow wound healing — a small cut took a week longer than usual to close. Now I skip rapamycin for 2 weeks if I’m going to have any procedure or significant skin trauma.
- Slight increase in upper respiratory bugs — possibly. Hard to separate from travel and Bangkok pollution.
- Better sleep on the dose night. Unexpected. Multiple anecdotal reports of this in the rapamycin community.
Things I expected and didn’t get: muscle loss, libido drop, brain fog, mood changes. None of these showed up at the weekly pulse dose. People who run rapamycin daily at transplant doses get all of these — that’s a different drug profile.
Sourcing — How to Actually Get a Prescription
Rapamycin is a real prescription drug — sirolimus. In the US, the legitimate paths are:
- Healthspan/longevity clinics (AgelessRx, Lifeforce, etc.) — they’ll do a video consult and prescribe off-label for healthy aging at $150–$300 for the consult plus the cost of the script.
- Your own GP — most won’t, but some will if you bring the literature and frame it as informed-consent off-label.
- International compounding pharmacies — easier outside the US.
In Thailand, where I split my time, rapamycin is available through specialty pharmacies with a Thai doctor’s prescription, which is significantly easier to obtain than a US script. Cost is roughly half. This is part of the broader pattern I covered in my piece on the peptide industry crackdown — Western regulatory friction is making serious longevity work cheaper and easier abroad.
Sourcing rapamycin grey-market — research-grade powder — is something I do not recommend. Unlike peptides, you cannot reliably verify rapamycin purity at home, and impurities in this drug class can do real damage. Pay for the prescription.
Stacking Rapamycin
What I actually run alongside rapamycin:
- Metformin — 500 mg twice daily. Different mechanism (AMPK upstream of mTOR), complementary. Some longevity researchers fight about whether they cancel each other; the consensus is they don’t.
- Acarbose — 50 mg with carb-heavy meals. Glucose excursion control. Fournier-Levesque level, not a Pattaya night-out cure.
- NAD+ precursors — see my NAD+ IV vs oral comparison. The mitochondrial side complements the autophagy side.
- TRT — does not interact problematically with weekly pulse rapamycin in any data I’ve seen.
- Senolytics — quercetin/fisetin pulse 2 days/month. Different mechanism, different cellular target.
What I do not stack with rapamycin: high-dose IGF-1 push protocols. If you’re running heavy MK-677 and chasing aggressive GH-driven muscle gain, rapamycin’s longevity case partially undoes itself. Pick a season for each: a building season, a longevity season.
Who Should Not Run Rapamycin
Honest list:
- Anyone trying to get pregnant or partnered with someone trying to get pregnant. mTOR plays a role in fetal development.
- Anyone with active or recently treated cancer. Get oncology guidance.
- Anyone immunocompromised already.
- Active surgery or wound healing situation.
- People who can’t be bothered with consistent bloodwork. This drug requires monitoring.
- Lifters chasing maximum hypertrophy who aren’t ready to accept the small risk to peak gains.
Bottom Line
Rapamycin at the weekly pulse dose is the most evidence-backed pharmaceutical longevity intervention available right now. It’s not magic. It’s not without trade-offs. The bloodwork moves and you have to track it. But two years in, my biomarkers are better than they were at 40, my training hasn’t suffered, and I’m running it for the same reason serious people run TRT — because the risk-adjusted upside on quality and length of life is too good to walk away from.
Get the prescription. Run the bloodwork. Start at 2 mg with grapefruit (or 6 mg without). Track everything for 12 weeks. Make the next decision with data, not vibes.