Quick facts

Safety: Rapamycin is safe for its FDA-approved uses when taken under the guidance of a healthcare provider. Its use for longevity purposes must be discussed with a professional. As it’s an immunosuppressant, not everyone will be eligible to take it

ITP results: Positive stage 1 and 2, also positive combined with metformin and acarbose (reaching a maximum of 29% with acarbose). Best performing substance in the trial.

(The Interventions Testing Program (ITP) is a peer-reviewed program designed to identify agents that extend lifespan and healthspan in mice)

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Some trials: 

NCT04488601 Participatory Evaluation (of) Aging (With) Rapamycin (for) Longevity Study

NCT04200911 Cognition, Age, and RaPamycin Effectiveness - DownregulatIon of thE mTor Pathway

NCT04742777 Effect of mTOR Inhibition & Other Metabolism Modulating Interventions on the Elderly [SubStudy Rapa & cMRI to Evaluate Cardiac Function]

NCT04608448 Topical-RAPA Use in Inflammation Reversal and Re-setting the Epigenetic Clock

NCT03946774 Dietary Protein and Monocyte/Macrophage Mammalian Target of Rapamycin (mTOR) Signaling

NCT05835999 Everolimus Aging Study

NCT03649698 Exercise and Nutrition for Healthy AgeiNg

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Some studies and publications: 

• Harrison, D.E., et al. (2009). Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature. This landmark study demonstrated that rapamycin extends the lifespan of middle-aged mice when treatment begins at 600 days of age, providing compelling evidence of its potential to extend lifespan in mammals.
• Miller, R.A., et al. (2011). Rapamycin, but not resveratrol or simvastatin, extends life span of genetically heterogeneous mice. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences. This study compared the effects of rapamycin with other potential anti-aging compounds and found that rapamycin uniquely extended the lifespan of genetically diverse mice.
• Kennedy, B.K., & Lamming, D.W. (2016). The Mechanistic Target of Rapamycin: The Grand ConducTOR of Metabolism and Aging. Cell Metabolism. This review provides an overview of the mTOR pathway's role in metabolism and aging, discussing how rapamycin's inhibition of mTOR contributes to its lifespan-extending effects.
• Kaeberlein, M., et al. (2015). Lifespan extension in yeast by complete removal of food. Aging Cell. While this study primarily focuses on calorie restriction in yeast, it discusses the role of nutrient-sensing pathways, including mTOR, in lifespan extension, providing context for rapamycin's effects.
• Mannick, J.B., et al. (2014). mTOR inhibition improves immune function in the elderly. Science Translational Medicine. This study explores the immunomodulatory effects of rapamycin in elderly humans, suggesting potential healthspan benefits beyond lifespan extension.
• Bitto, A., et al. (2016). Transient rapamycin treatment can increase lifespan and healthspan in middle-aged mice. eLife. This study suggests that even short-term treatment with rapamycin in middle age can have lasting effects on lifespan and healthspan, indicating potential for intermittent dosing strategies.

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Overview: Rapamycin works primarily through its inhibition of the mammalian target of rapamycin (mTOR) pathway, which is a central regulator of cell growth, protein synthesis, autophagy, and metabolism. It also plays a crucial role in responding to nutrients, growth factors, and energy status within cells. The pathway has two distinct complexes, mTORC1 and mTORC2, with mTORC1 being the primary target of rapamycin.

Type of substance: Approved for use primarily as an immunosuppressant. Its use for longevity is still off-label. As such, it cannot be obtained without a medical prescription.

Rapamycin is a macrolide compound that was originally discovered in a soil sample from Easter Island in the early 1970s. It’s produced by the bacterium Streptomyces hygroscopicus. Chemically, rapamycin is known for its complex structure, which includes a large macrocyclic lactone ring.

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‍Other related: Metformin, Acarbose, AKG Alpha ketoglutarate