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Our read is that taking rapamycin is Well Supported for longevity, with evidence suggesting lifespan extension and immune benefits, though potential side effects and optimal dosing require careful consideration.
Our read is that rapamycin has demonstrated efficacy in extending lifespan across various model systems and in mice, with some human trials showing healthspan improvements.
It primarily functions by tamping down maladaptive inflammation, enhancing autophagy, and altering protein translation, potentially restoring youthful immune function.
However, concerns exist regarding metabolic disruptions, increased infection risk, and potential negative effects on lipids and blood glucose, necessitating careful monitoring and consideration of individual health profiles.
Peter Attia has been taking rapamycin for two and a half years, using a once-weekly dosing regimen of 5mg to 8mg. The University of Tennessee veterinary group uses a rapamycin dosing strategy for dogs of 0.1 mg/kg. Novartis hypothesized that dosing rapamycin once weekly reduces side effects by allowing trough levels to bottom out. The optimal human dose for rapamycin may be around 0.1 milligrams per kilogram weekly.
Bryan Johnson stopped taking rapamycin after four years due to negative effects on lipids, blood glucose, resting heart rate, and small tissue infections. Rapamycin has potential side effects including metabolic disruptions, high cholesterol, tissue swelling, soft tissue infections, and impaired wound healing (Bryan Johnson). Longer-term exposure to rapamycin or rapologs (1 week to 1 month) can lead to consequences of mTORC2 inhibition, such as hyperglycemia and hypertriglyceridemia (Peter Attia). Rapamycin's inhibition of natural killer cells raises concerns about anti-cancer immune surveillance and increased cancer risk (Bryan Johnson). The widespread use of rapamycin may lead to an increase in overall infections, including tuberculosis and pulmonary infections (Paul Saladino). High doses of rapamycin in animals may promote immune cancers (Peter Attia). Limiting mTOR, drastically lowering insulin, or having no IGF-1 can lead to negative health consequences such as immunologic issues, hormonal imbalances, electrolyte problems, sleep apnea, and sleep issues (Paul Saladino). Valter Longo is not enthusiastic about working with rapamycin due to concerns about blocking central cellular metabolism and potential side effects like hyperglycemia, testicular degeneration, and cataracts (Peter Attia, Rhonda Patrick). Rapamycin should not be taken by individuals around 40 years old, as mouse studies were conducted on older equivalents (Peter Attia).
The safety of stacking NDGA with autophagy enhancers like rapamycin and metformin is unclear (Bryan Johnson). The effects of low-dose rapamycin on insulin sensitivity are uncertain (Peter Attia). The efficacy of rapamycin in viral infections like influenza and COVID-19 is uncertain (Peter Attia). Rapamycin may cause changes in the methylation patterns of T-cells, potentially indicating a reversal of biological aging in the epigenome (Peter Attia).
Encapsulated rapamycin was effective in extending lifespan in both late middle-aged and younger mice.
Rapamycin's life-extending effects have been replicated across various model systems, including yeast, fruit flies, and worms.
Pharmacologic inhibition of mTOR with rapamycin or its analogs shows promise for lifespan and healthspan improvement, even when initiated late in life.
High doses of rapamycin (e.g., 20mg weekly) are immunosuppressive and potentially interfere with vaccine response.
The effect size is large enough to matter clinically, not just statistically.
Animal-model results don't translate to the human protocol being recommended.
Animal-model results don't translate to the human protocol being recommended.
Confounding and publication bias inflate the apparent benefit.
Animal-model results don't translate to the human protocol being recommended.
Confounding and publication bias inflate the apparent benefit.