Rapamycin

TL;DR

Rapamycin is a natural compound originally discovered in soil bacteria on Easter Island (Rapa Nui).
Inhibits mTOR (mechanistic target of rapamycin), a key growth and ageing pathway.
Extends lifespan in yeast, worms, flies, and mice — one of the strongest known pharmacological interventions for longevity.
Clinically used as an immunosuppressant (transplant medicine) and anti-cancer drug.
Under active research for anti-ageing, cardiovascular health, neuroprotection, and metabolic benefits.
Risks include immune suppression, mouth ulcers, and glucose dysregulation at high or chronic doses.

At-a-Glance Facts

Entity Type: Drug / Natural Compound
Discovered: 1972, soil samples from Rapa Nui (Easter Island)
Approved Uses: Organ transplant rejection prevention, certain cancers, rare diseases (tuberous sclerosis complex)
Mechanism: Inhibits mTORC1 (and partially mTORC2 with chronic use), shifting cells from growth to repair mode
Hallmarks of Ageing Impacted: Deregulated nutrient sensing, loss of proteostasis, mitochondrial dysfunction, cellular senescence

What is Rapamycin?

Rapamycin (also called Sirolimus) is a macrolide compound that binds to FKBP12 and inhibits mTORC1.

mTORC1 inhibition: Reduces growth, increases autophagy, and enhances stress resistance.
mTORC2 inhibition: With prolonged use, can cause insulin resistance and glucose imbalance.

Because mTOR is a central ageing pathway, rapamycin has become one of the most studied geroprotectors.

Rapamycin and Ageing

Lifespan Extension: Robustly extends lifespan in yeast, worms, flies, and mice.
Healthspan Benefits: Improves immune function in older mice and reduces age-related diseases.
Hallmarks of Ageing Impacted:
Nutrient Sensing: Directly suppresses mTORC1.
Proteostasis: Increases autophagy, clearing misfolded proteins.
Mitochondria: Enhances quality control and function.
Senescence: Reduces SASP and pro-inflammatory signalling.

Biological Functions & Mechanisms

mTOR Inhibition: Shifts balance from growth to maintenance.
Autophagy Induction: Promotes cellular recycling and repair.
Protein Homeostasis: Reduces misfolded/aggregated proteins.
Immune Modulation: Suppresses overactive immune responses.
Metabolic Effects: Alters insulin sensitivity and lipid metabolism.

Current & Potential Uses

Approved Medical Uses

Transplant Medicine: Prevents rejection by suppressing immune activation.
Cancer Therapy: Slows tumour growth in some cancers.
Rare Diseases: Approved for lymphangioleiomyomatosis and tuberous sclerosis complex.

Longevity Research Applications

Lifespan Extension: Demonstrated across multiple species.
Immune Rejuvenation: Improves vaccine response in elderly humans.
Neuroprotection: Investigated for Alzheimer’s and Parkinson’s.
Cardiovascular Health: Reduces age-related vascular stiffening.
Metabolic Benefits: Lowers obesity-driven inflammation (though may impair glucose handling with chronic use).

Interventions & Stacking with Rapamycin

Lifestyle Synergies: Fasting, calorie restriction, and exercise act on overlapping pathways.
Nutritional Compounds: Resveratrol, quercetin, spermidine, and berberine mimic some rapamycin effects.
Senolytics: Potential complementary use to target senescent cells.

Safety and Considerations

Side Effects: Mouth ulcers, slow wound healing, elevated triglycerides, insulin resistance (chronic high dose).
Immune Suppression: At clinical transplant doses, risk of infections increases.
Dosing in Longevity Research: Intermittent, lower doses may reduce side effects while retaining benefits (still experimental).
Human Longevity Trials: Ongoing — no proven lifespan extension in humans yet.

Discovery and Research History

1972: Isolated from Streptomyces hygroscopicus on Rapa Nui soil samples.
1999: FDA-approved as an immunosuppressant.
2009: Landmark mouse studies show lifespan extension.
2010s–present: Explored as an anti-ageing and healthspan intervention.

FAQs

Does rapamycin extend human lifespan?
Not proven yet — but evidence from animals is compelling.

Is rapamycin safe to take for longevity?
Not approved for anti-ageing use. Medical supervision required.

What’s the difference between rapamycin and rapalogs?
Rapalogs (everolimus, temsirolimus) are modified versions with similar but distinct properties.

How does rapamycin compare to calorie restriction?
They overlap via mTOR inhibition, but rapamycin can mimic some benefits without reducing calories.

Glossary

mTOR (mechanistic Target of Rapamycin): Growth pathway inhibited by rapamycin.
Autophagy: Cellular recycling process boosted by rapamycin.
FKBP12: Protein that binds rapamycin to inhibit mTOR.
Rapalogs: Rapamycin analogues developed for cancer therapy.

Schema (JSON-LD: Drug)

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"@type": "Drug",

"name": "Rapamycin (Sirolimus)",

"description": "Rapamycin is a natural compound that inhibits mTOR, extending lifespan in animal models and showing promise for human longevity. Clinically used as an immunosuppressant and anti-cancer drug.",

"mechanismOfAction": "mTORC1 inhibition, autophagy induction, metabolic regulation",

"legalStatus": "FDA-approved for transplant and cancer; experimental in longevity",

"possibleTreatment": ["Organ transplant rejection", "Cancer", "Tuberous sclerosis complex"],

"sameAs": [

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Cross-Linking (Knowledge Graph Anchors)

From this page, link internally to:

mTOR (direct target of rapamycin)
Autophagy (activated by rapamycin)
AMPK (complementary nutrient-sensing pathway)
Senescence (reduced by rapamycin)
Calorie Restriction / Fasting (parallel interventions)
Spermidine, Resveratrol, Quercetin, Metformin (nutritional/pharma mimetics)
Hallmarks of Ageing (nutrient sensing, proteostasis, mitochondrial dysfunction)

This frames Rapamycin as the most validated pharmacological longevity intervention, bridging natural discovery, clinical medicine, and ageing research.

Would you like me to also prepare a separate entity page on Rapalogs (Everolimus, Temsirolimus, etc.), since they are increasingly studied as longevity alternatives with different side-effect profiles?