# Rapamycin

Rating: Early — Mostly animal or cell studies; few or uncontrolled human data
Type: Compound
Updated: 2026-10-15
Canonical: https://heretic.bio/articles/rapamycin-mtor-inhibition-pearl-trial-evidence-and-clinical-translation.html

> Rapamycin (sirolimus) is an FDA-approved transplant drug now prescribed off-label at low intermittent doses for longevity. The animal data are the best in geroscience, with 9-30% mouse lifespan extension, but no human trial has shown a lifespan benefit. The two key human trials are PEARL (n=114, safe, modest lean-mass and pain signals in women) and RAPA-EX-01 (n=40, weekly dosing attenuated exercise training gains in sensitivity analyses). The open question has shifted from safety to dosing interval.

## Executive Summary

Rapamycin (sirolimus) is an FDA-approved immunosuppressant now prescribed off-label for longevity at low, intermittent doses (~5–10 mg/week). Human evidence now rests on four pillars: (1) the **PEARL trial** (48 weeks, weekly compounded rapamycin, relatively safe, lean-mass and pain signals in women); (2) the **RAPA-EX-01 trial** (April 2026) — the first RCT to combine weekly sirolimus with structured exercise in older adults, which found 6 mg/week did _not_ enhance and in sensitivity analyses **attenuated** training gains; (3) everolimus immune-remodeling RCTs (Mannick et al.); and (4) the ongoing **VIBRANT** ovarian-aging and canine **TRIAD** trials. The central open question has shifted from "is intermittent rapamycin safe?" to "**what dosing interval preserves exercise adaptation while retaining geroprotection?** " — with RAPA-EX-01's authors now proposing 3–6-week interdose intervals.

## Molecular Mechanism (Summary)

  * Sirolimus is an allosteric inhibitor of **mTORC1** (FKBP12 complex); mTORC2 inhibition only after prolonged exposure — the basis for intermittent scheduling.
  * mTORC1 inhibition → reduced S6K1/4E-BP1 signaling → reduced protein synthesis, **increased autophagy** , reduced senescence-associated secretory phenotype (SASP).
  * Tension: mTORC1 is also the central anabolic driver of muscle hypertrophy; exercise and rapamycin act on the same node in opposite directions. See 11 - Longevity and Anti-Aging/mTOR and AMPK Pathways and 11 - Longevity and Anti-Aging/Autophagy.



## Lifespan Data (Preclinical)

  * Mice: Harrison et al. 2009 — 9–14% lifespan extension; Miller et al. 2011 (J Gerontol A) — rapamycin, but not resveratrol or simvastatin, extends lifespan in heterogeneous mice.
  * Bitto et al. 2016 (eLife 5:e16351): **transient** midlife treatment increases lifespan and healthspan in mice — key precedent for intermittent human dosing.
  * Partial mTORC1 inhibition reverses sarcopenia in rodents (muscle mass + fiber CSA up, senescence/denervation gene programs down) — cited in RAPA-EX-01 as the optimistic counterweight.
  * A single large rapamycin dose abolishes post-exercise muscle protein synthesis in young men (classic human anabolic-blocking study, ref [7] of RAPA-EX-01).
  * Monkeys: supportive but limited; translational gap remains.



## PEARL Trial (Human, 2025) — Primary Source

**Citation** : Moel M, et al. Influence of rapamycin on safety and healthspan metrics after one year: PEARL trial results. Aging (Albany NY). 2025 Apr;17(4):908–936. doi [10.18632/aging.206235](https://doi.org/10.18632/aging.206235). PMCID: [PMC12074816](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12074816/). **PMID[40188830](https://pubmed.ncbi.nlm.nih.gov/40188830/)**.

  * Decentralized, double-blind RCT ([NCT04488601](https://clinicaltrials.gov/study/NCT04488601)); 48 weeks; n=114 completers (50–85 y); placebo / 5 mg / 10 mg **compounded** weekly.
  * Safety (primary): AE counts balanced (117/116/122); GI slightly higher; compounded bioavailability ~⅓ of commercial sirolimus (effective under-dosing caveat).
  * Signals: women 10 mg — lean mass ↑ (ηp²=0.202, p=0.013; OR=28 for improvement, p=0.008) and pain ↓ (SF-36, p=0.015); 5 mg — General Health/Emotional Well-being ↑; visceral fat (primary) null; epigenetic clocks (TruAge, n=24) null; minor microbiome shifts.
  * Limitations: small female n, self-reported adherence, health-conscious cohort, formulation under-dosing.



## RAPA-EX-01 (April 2026) — Rapamycin + Exercise RCT ⚠️ Key Update

**Citation** : Stanfield B, Leroux B, Kaeberlein M, Jones J, Lucas R. Exercise and Weekly Sirolimus (Rapamycin) in Older Adults: RAPA-EX-01 Randomised, Double-Blind, Placebo-Controlled Trial. J Cachexia Sarcopenia Muscle. 2026 Apr 15;17(2):e70274. doi [10.1002/jcsm.70274](https://doi.org/10.1002/jcsm.70274). PMCID: [PMC13082878](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13082878/). **PMID[41985884](https://pubmed.ncbi.nlm.nih.gov/41985884/)**. Registration: ACTRN12624000790549 (protocol published in _Trials_).

**Design** : Single-centre (Aotearoa Clinical Trials Trust, Auckland NZ); n=40 sedentary adults 65–85 y (mean 72.2; 47.5% female); 1:1 sirolimus **6 mg once weekly** (3×2 mg Rapamune) vs matched placebo × 13 weeks. Both arms did identical home-based exercise 3×/week: chair-stand "density training" + exercycle (10→25 min progressive). **Dosing deliberately timed "Day 6" — ~24 h after the final weekly exercise session** — a direct test of the _hypothesis_ (alternate mTORC1 activation with inhibition).

**Results** : \- Primary (30-s chair-stand, ITT): adjusted difference **−2.13 reps** (95% CI −4.61 to 0.34; p=0.089) favoring placebo. \- Sensitivity: complete-case **−2.46** (p=0.045); per-protocol **−3.44 reps** (95% CI −5.86 to −0.99; **p=0.007**). \- 6MWD −4.87 m (p=0.706); grip −1.13 kg (p=0.344) — both non-significant, direction favored placebo. \- CRP: +4.26 mg/L nominal excess **driven entirely by 2 outliers** (17 and 50 mg/L); Epigenetic clocks (TruDiagnostics): mixed, non-significant. - Labs (statistically significant, clinically modest): MCV −2.90 fL (p<0.001); platelets +17.6×10⁹/L (p=0.025); ALP +5.56 U/L (p=0.012); **LDL +0.32 mmol/L (p=0.036)** ; HbA1c +1.74 mmol/mol (p=0.030). \- Safety: 17/20 (85%) per arm with ≥1 AE, but total burden **99 vs 63 events** (sirolimus vs placebo); **one possibly drug-related SAE (pneumonia)**.

## Women's Health / Ovarian Aging (VIBRANT + IVF)

  * **VIBRANT** ([NCT05836025](https://clinicaltrials.gov/study/NCT05836025); Columbia, PI Zev Williams / Yousin Suh): n=50 healthy women 38–45 with regular cycles, weekly oral rapamycin vs placebo. Primary completion **Oct 2025** (actual); study completion est. **Sep 2026** ; CT.gov last updated Dec 2025. Early institutional reporting (Columbia OBGYN 2024 annual report): ovarian aging slowed ~**20%** , monthly follicle loss ~50→~15 (press-level claim; peer-reviewed publication pending).
  * Mechanistic backdrop: Li J et al. 2025, Cell Reports Medicine 6(11):102424 — ribosome dysregulation in age-related infertility as an mTOR-linked target.
  * A late-2025 IVF RCT in women with prior failed cycles is reported as showing improved reproductive outcomes with short-term mTOR inhibition (secondary-source summary; primary citation to be captured on library update).
  * Converges with PEARL's female-specific lean-mass and pain signals: **rapamycin's strongest human signals are currently in women** — a differentiation angle for women's-healthspan clinics.



## Canine TRIAD (Dog Aging Project)

  * Urfer et al. 2017 (Geroscience 39:117–127): 24 middle-aged dogs, 10-week low-dose rapamycin — improved cardiac systolic function, good safety.
  * Coleman et al. 2025 (Geroscience 47(3):2851–2877): TRIAD design paper — n=580 target, dogs ≥7 y / 44–120 lb, multicentre, ~3-year, double-masked, placebo-controlled; primary outcomes include survival, mobility, cognition, cancer incidence. Recruiting; no primary results yet.
  * Companion translational read-out for human dosing debates (intermittent schedules in large mammals).



## Uses

Rationale | Status  
---|---  
PEARL-tested; S6K1 inhibition ≥5–7 d | Most common off-label; RAPA-EX-01 cautions with concurrent training  
— | **Tested — attenuation signal** (RAPA-EX-01)  
Lower cumulative mTOR suppression; clinical-judgment variant | Untested head-to-head  
Near-complete clearance; immune/anabolic recovery | Proposed by RAPA-EX-01 authors; untested  
Continuous immunosuppression | Approved indications only  
  
  * See 11 - Longevity and Anti-Aging/Rapamycin Dosing Protocols for the protocol-level intelligence file.



## Systematic-Review Framing

  * Lee DJW, Kuerec AH, Maier AB. Lancet Healthy Longev 2024;5(2):e152–e162: rapalogs improved **immune, cardiovascular, integumentary** parameters in healthy older adults — but **not** endocrine, muscular, or neurological systems.
  * RAPA-EX-01 is now the sharpest data point behind that "not muscular" verdict for concurrent-training users.
  * Off-label use is growing via longevity clinics/telehealth while FDA reviews nothing for an aging indication; malpractice-exposure analysis remains relevant for prescribers.



## Competitive Landscape

  * Vs. senolytics (D+Q, fisetin): senolytics act on cell clearance, not anabolic signaling — no exercise-blunting signal to date; see 01 - Peptides/Senolytic Therapeutics - Evidence and Competitive Landscape.
  * Vs. NAD+ precursors: different mechanism (substrate vs. pathway inhibition); NAD+ market in credibility crisis (01 - Peptides/NAD+ Precursor Market in Crisis - Nature Metabolism 2026).
  * Vs. partial epigenetic reprogramming: earlier-stage, no clinic deployment yet.
  * Complementarity question: whether senolytics + spaced-dose rapamycin can decouple geroprotection from anabolic interference is now the live research program.



## Claims Audit & Regulatory Status

  * Off-label prescribing for longevity: growing, no FDA aging indication, no malpractice case law specific to longevity dosing.
  * Clinics claiming "proven lifespan extension" in humans: unsupported — mouse-only claim; PEARL/RAPA-EX-01 show modest, mixed healthspan signals at best.
  * Compounded formulations (PEARL) can under-deliver ~66% vs commercial sirolimus — a quality/audit angle shared with 01 - Peptides/Peptide Sources and Quality.



## Personalization Angles

  * **AgelessRx / Dr. Stefanie Morgan** : PEARL co-authors — pitch co-branded clinical translation guide covering RAPA-EX-01 interval implications.
  * **Dr. Brad Stanfield** : first-author GP with large audience — the every-3–6-week dosing proposal is his current talking track; natural collab target for protocol content.
  * **Siim Land** : covers mTOR — pitch evidence pack with PEARL + RAPA-EX-01 trade-off framing.
  * **Women's healthspan angle** : PEARL female signals + VIBRANT + IVF RCT — differentiated content lane with far less competition than generic longevity.
  * **Next Next: canine longevity content** (TRIAD) — pet-owner crossover audience for biohacking brands.



_Primary-source focused; no medical advice. Evidence current as of 2026-08-24._

## Rapamycin: Regimens Studied in Trials

> Rapamycin (sirolimus) is the most extensively studied pharmacological longevity intervention in model organisms, with emerging — though still preliminary — human evidence. This file covers dosing paradigms for longevity applications, with emphasis on the critical distinction between transplant/medical doses and the much lower intermittent doses used in the longevity context.

* * *

### Mechanism: Why Rapamycin Targets Aging

Rapamycin inhibits **mTOR (mechanistic Target of Rapamycin)** , a central nutrient-sensing kinase that exists in two structurally and functionally distinct complexes:

### mTORC1 — The Growth/Repair Switch

Property | Description  
---|---  
**Senses** | Amino acids (especially leucine), growth factors, ATP, oxygen  
**Activates** | Protein synthesis (S6K1, 4E-BP1), lipid synthesis, mitochondrial biogenesis  
**Inhibits** | Autophagy, lysosomal biogenesis, stress response genes  
**When active** | Cell growth, proliferation — the "anabolic" state  
**When inhibited** | Autophagy induction, metabolic reprogramming, longevity-associated gene expression  
  
**Key insight** : mTORC1 inhibition shifts cellular physiology from growth/accumulation toward cellular repair and recycling. This shift is central to the longevity effect observed across species.

### mTORC2 — Metabolic Regulation

Property | Description  
---|---  
**Senses** | Growth factors (insulin, IGF-1)  
**Functions** | Insulin signaling, cytoskeletal organization, cell survival  
**Concern** | Rapamycin at high doses or chronic use inhibits mTORC2, causing metabolic dysregulation  
  
**The critical therapeutic window** : Selective mTORC1 inhibition without significant mTORC2 inhibition is the goal of longevity-oriented dosing. Intermittent, low-dose regimens aim to achieve this selectivity.

### The mTOR/AMPK See-Saw
    
    
    High nutrients / Growth factors → mTORC1 ACTIVE → Protein synthesis, growth
                                  ↓
    Low nutrients / Energy stress → AMPK ACTIVE → Autophagy, fatty acid oxidation
                                  ↓
    Both pathways respond to cellular energy status, creating a metabolic rheostat
    

Rapamycin tips this balance toward AMPK-dominant, autophagy-promoting state.

* * *

### Animal Data

Species | Effect | Dose | Notes | PMID  
---|---|---|---|---  
Mice (multiple strains) | 10-30% lifespan extension | Various | Most robust effect in female C57BL/6J | 25908634  
Mice (late-life initiation) | 9-14% extension when started at 600 days | Intermittent | Effect persists even when started mid-life | 29652921  
Dogs (Dog Aging Project) | 0.15 mg/kg/week — ongoing | Intermittent | Lifespan endpoint pending; healthspan markers improved | 30820546  
Yeast | ~50% replicative lifespan extension | Low dose | Historical first observation | —  
C. elegans | Modest extension | Dose-dependent | Best with pulsed exposure | —  
  
### Human Evidence

Study | Population | Finding | Limitations | PMID  
---|---|---|---|---  
PEARL trial (everolimus) | Elderly (65+) | Increased influenza vaccine response, reduced senescent T cells | Small n, surrogate endpoints | 31734926  
Transplant patients (long-term) | Various | Increased infection risk, metabolic effects at high doses | Not longevity-dosed | —  
Rapamycin off-label survey | Self-selected longevity users | Self-reported improvements in pain, fatigue, cognition | Significant reporting bias | —  
  
**Summary** : No RCT has demonstrated lifespan extension in humans. Human evidence is limited to surrogate endpoints (immune function, markers of senescence) and mechanistic plausibility. Proceed with appropriate caution.

* * *

### Doses in studies

The most influential longevity dosing framework comes from **Mikhail Blagosklonny** (Roswell Park), who has argued since 2010 that:

  1. **Weekly dosing achieves sufficient mTORC1 inhibition while sparing mTORC2**
  2. **The goal is "young-old" mTORC1 activity — enough to inhibit tumor growth and cellular senescence without the costs of full immunosuppression**



**Blagosklonny Protocol** : \- **Dose** : 5-10 mg once per week (for a 70 kg adult) \- **Target** : ~20-30% of transplant-level immunosuppression \- **Rationale** : Maintains enough mTORC1 inhibition for autophagy induction without impairing mTORC2-dependent insulin signaling \- **Blood level target** : <10 ng/mL (well below the 20-40 ng/mL targeted in transplant patients)

### Doses in studies

Kaeberlein's group at the University of Washington, running the Dog Aging Project and related human work, has published the following framework:

**Key monitoring** : \- Fasting lipid panel (rapamycin ↑ triglycerides in some subjects) \- Fasting glucose / HbA1c (mTORC2 inhibition → insulin resistance risk) \- Complete blood count (immunosuppression monitoring) \- Whole blood rapamycin trough level (if available; target <10 ng/mL)

### Doses in studies

The Dog Aging Project uses **0.15 mg/kg once weekly** , which was selected to: \- Achieve meaningful mTORC1 inhibition \- Remain below the threshold for immunosuppression \- Be practical for owner administration \- Show acceptable safety in a 12-month toxicity study in beagles

### Uses

Context | mTORC1 | mTORC2 | Immunosuppression  
---|---|---|---  
**Transplant** | ++++ | +++ | Full  
**Longevity (Blagosklonny)** | +++ | ± | Minimal  
**Longevity (Dog Aging)** | +++ | ± | Minimal  
**Everolimus (PEARL)** | +++ | ± | Mild  
  
* * *

### Pharmacokinetics

Parameter | Value  
---|---  
**Half-life** | 57-62 hours (mean ~60 hours)  
**Time to steady state** | 7-14 days (with daily dosing)  
**Metabolism** | CYP3A4 (liver), primarily excreted in feces  
**Bioavailability** | ~14% (oral solution, fasted); increased with high-fat meal  
**Peak concentration** | 1-2 hours after oral dose  
**Duration of mTORC1 inhibition** | Pharmacodynamic effect extends well beyond plasma half-life  
  
**Important** : mTORC1 inhibition from a single dose persists for several days, meaning weekly dosing maintains continuous (though pulsatile) mTORC1 inhibition.

* * *

### Approaches Reported in the Literature

Side Effect | Management  
---|---  
**Mouth ulcers (aphthous)** | Topical dexamethasone rinse; reduce dose  
**Triglyceride elevation** | Omega-3s, dietary modification; monitor  
**Glucose dysregulation** | Monitor HbA1c; discontinue if pre-diabetes worsens  
**Mild immunosuppression** | Low dose rarely clinically significant  
**GI upset** | Studies administered if needed  
**Skin effects** | Acne, rash (usually self-limiting)  
  
### Contraindications and Cautions

Situation | Concern  
---|---  
**Pregnancy** | Contraindicated — teratogenic in animal models  
**Active infection** | May impair immune response  
**Pre-existing liver disease** | CYP3A4 metabolism affected  
**Concurrent CYP3A4 inhibitors** | Ketoconazole, erythromycin, grapefruit → ↑ rapamycin levels  
**Concurrent CYP3A4 inducers** | Rifampin, phenytoin → ↓ rapamycin levels  
**Patients on warfarin** | Monitor INR; interaction reported  
  
### Drug Interactions

Interacting Drug | Effect  
---|---  
**Ketoconazole, itraconazole** | ↑ rapamycin AUC 4-5x — **avoid**  
**Erythromycin, clarithromycin** | ↑ rapamycin AUC — **avoid**  
**Rifampin** | ↓ rapamycin AUC — **avoid**  
**Grapefruit** | ↑ bioavailability ~30% — **avoid**  
**High-fat meal** | ↑ absorption — keep consistent  
**Proton pump inhibitors** | Variable; monitor  
**Calcium channel blockers** | Diltiazem, verapamil — ↑ levels; monitor  
  
* * *

### Blood Level Monitoring

For longevity use, monitoring rapamycin whole blood trough levels is prudent:

Context | Target Trough Level  
---|---  
Longevity (intermittent, low) | <10 ng/mL  
PEARL trial | ~5-8 ng/mL  
  
**Note** : Most clinical labs can measure rapamycin/sirolimus levels. Trough levels are most reliable when drawn immediately before the next scheduled dose.

* * *

### Combination Approaches

Rapamycin is increasingly used in combination with other longevity interventions:

### Rapamycin + Metformin

Rationale | Mechanism  
---|---  
**Complementary mTOR pathways** | Metformin activates AMPK; rapamycin inhibits mTORC1  
**Metabolic benefits** | Metformin mitigates rapamycin's glucose effects  
**Clinical use** | Often co-prescribed; both started at low dose  
  
### Rapamycin + Senolytics (Dasatinib + Quercetin)

Rationale | Mechanism  
---|---  
**Different anti-senescence mechanisms** | Senolytics kill existing senescent cells; rapamycin prevents their accumulation  
**Timing** | Senolytic course (D+Q) 3 days/month + weekly rapamycin  
**Evidence** | Preclinical only; combination in TAME trial pending  
  
### Rapamycin + NAD+ Precursors (NMN/NR)

Rationale | Mechanism  
---|---  
**Autophagy + sirtuin activation** | Rapamycin induces autophagy; NAD+ precursors support sirtuins  
**Mitochondrial health** | Both pathways converge on mitochondrial function  
**Caveat** | Competing metabolic effects — theoretical  
  
### Rapamycin + Fasting / FMD

Rationale | Mechanism  
---|---  
**Synergistic autophagy** | Both activate autophagy through different pathways  
**Fasting-mimicking** | FMD cycles may reduce mTOR between rapamycin doses  
**Approach** | Dose rapamycin at end of 24-36 hour fast  
  
* * *

### Older Adults (>65)

  * May benefit more from immune-senescence effects
  * Start at lower end of dosing range
  * Monitor for metabolic effects more closely
  * Some sources discuss rapa + flu vaccine combination (everolimus data)



### Middle-Aged (40-65)

  * Most common demographic for off-label longevity use
  * Foundation should be lifestyle first (exercise, sleep, nutrition)
  * Some sources discuss rapamycin only after optimizing foundations



### Younger Adults (<40)

  * Generally not recommended for longevity purposes
  * May be appropriate for specific conditions (autoimmune, rare diseases)
  * mTOR is essential for development and growth — inhibition theoretically concerning in reproductive-age women



### Cancer Patients / Survivors

  * **Active cancer** : Generally contraindicated — may protect cancer cells
  * **Cancer survivors** : Discuss with oncologist; some evidence for prevention but timing critical
  * **History of pre-malignant conditions** : May be appropriate; individual assessment



### Diabetes / Metabolic Syndrome

  * **Pre-diabetes** : Monitor glucose carefully; rapamycin can worsen insulin resistance
  * **Type 2 diabetes** : Use with extreme caution; metformin co-administration often necessary
  * **Metabolic syndrome features** : Optimize metabolic health before starting



* * *

### Notes

  * **Human lifespan data** : Does not yet exist. All longevity claims are based on preclinical data, mechanistic reasoning, and surrogate endpoints.
  * **Off-label use** : Rapamycin is FDA-approved for transplant rejection and renal cell carcinoma; longevity use is entirely off-label
  * **Compounding pharmacies** : Reliable compounding sources exist; verify quality and third-party testing
  * **The TAME trial (Targeting Aging with Metformin)** : While metformin-focused, may establish regulatory pathway for longevity drugs; rapamycin inclusion was discussed but not adopted
  * **Bovine vs. rabbit vs. human studies** : Much of the mechanistic data is from mice — human responses may differ substantially
  * **mTORC2 inhibition concern** : The most legitimate safety concern with chronic rapamycin use — metabolic effects may outweigh benefits if mTORC2 is significantly inhibited



* * *

### Getting Started

  1. **Baseline labs** : CBC, CMP, fasting glucose, HbA1c, lipid panel, creatinine
  2. **Consult a knowledgeable physician** : Off-label prescribing requires a doctor willing to monitor
  3. **Studies started low** : 2-3 mg test dose, assess for GI side effects
  4. **Monitor** : Repeat labs at 4 weeks, then every 3 months
  5. **Hold during illness** : Major infection, surgery — immunosuppression concern



### Sourcing

  * **Rapamune** (Pfizer) — FDA-approved, expensive, reliable quality
  * **Compounded sirolimus** — Significantly cheaper; use reputable 503B pharmacy
  * **International pharmacies** — Lower cost but verify regulatory status



### Contraindications Absolute

  * Pregnancy or plans to become pregnant
  * Active severe infection
  * Known hypersensitivity to rapamycin



* * *

### Connection to Other Files

  * [Metformin and Rapamycin](metformin-and-rapamycin.html) — Detailed mechanisms, comparisons, combination rationale
  * [mTOR and AMPK Pathways](mtor-and-ampk-pathways.html) — The metabolic switches rapamycin targets
  * [Autophagy](autophagy.html) — Cellular cleaning mechanism enhanced by rapamycin
  * [Senolytics](senolytics.html) — Combining with dasatinib + quercetin
  * [Overview - Longevity Science](longevity-science-overview.html) — Hallmarks of aging framework
  * [NAD+ and Sirtuin Activators](nad-and-sirtuin-activators.html) — Overlapping mitochondrial interventions



* * *

## Sources

1. DOI 10.18632/aging.206235 (DOI 10.18632/aging.206235)
2. Moel M, et al. Aging (Albany NY) 2025;17(4):908–936. PMID 40188830 / PMC12074816 . (PEARL) (PMC12074816, PubMed 40188830)
3. NCT05836025 (VIBRANT; results posting pending); ACTRN12624000790549 (RAPA-EX-01); NCT04488601 (PEARL). (NCT04488601, NCT05836025)
4. DOI 10.1002/jcsm.70274 (DOI 10.1002/jcsm.70274)
5. Stanfield B, Leroux B, Kaeberlein M, Jones J, Lucas R. J Cachexia Sarcopenia Muscle 2026;17(2):e70274. PMID 41985884 / PMC13082878 . (RAPA-EX-01) (PMC13082878, PubMed 41985884)