Rapamycin Therapy
Rapamycin has become the most promising longevity medication. Animal studies show up to a 14% increase in lifespan. Rapamycin was first discovered in 1964 on Easter Island (known as Rapa Nui); after decades of research, it became FDA-approved as an immune-modulating drug in 1999. Today, it's the go-to longevity therapy for those who live on the cutting edge.
Experts say:
"[Rapamycin] is the most robust and reproducible drug that we know about today for impacting not only longevity, but ... rapamycin also seems to positively impact pretty much every aspect of health span that we measure."
Matt Kaeberlein
"Rapamycin is under active investigation for its ability to extend lifespan on many different species...[there are many clinicians] who are quite excited about the potential for rapamycin."
Andrew Huberman
"The overwhelming evidence suggests that Rapamycin is a universal anti-aging drug – that is, it extends lifespan in all tested models from yeast to mammals, suppresses cell senescence and delays the onset of age-related diseases, which are manifestations of aging."
Mikhail Blagosklonny
"Small doses of Rapamycin given to mice when they were already in their final months of their normal lives results in 9% to 14% longer lives ... which translates to about a decade of healthy human life."
David Sinclair
Rapamycin Research
Rapamycin fed late in life extends lifespan in genetically heterogeneous mice
Harrison DE, et. al
Evaluation of off-label rapamycin use to promote healthspan in 333 adults
Kaeberlein TL, et. al
Rapamycin for longevity
Blagosklonny MV
Effect of rapamycin on aging and age-related diseases-past and future
Selvarani R, et. al
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Frequently asked questions
What is Rapamycin?
Rapamycin is a drug in the Macrolide family - the same family of drugs as Azithromycin (known commonly as the “Z-pack”. Rapamycin was isolated from the bacteria Streptomyces Hygroscopicus on Easter Island (known as Rapa Nui by the native population). Rapamycin was first developed as an antifungal agent but was later popularized as an immune modulating drug to prevent organ rejection in transplant patients.
What Does Rapamycin Have to Do with longevity?
As mentioned above, Rapamycin has primarily been used as an immunomodulator for patients who have undergone solid organ transplants. A closer look at the mechanism of action of Rapamycin, however, reveals a possible link to longevity. Inside the human cell, Rapamycin binds to a special target called the Mechanistic Target of Rapamycin 1 or mTOR1. mTOR1 is a compound composed of several molecules that, together, are central to cellular anabolism (building) and catabolism (removal and recycling). It is one of our most important and multifunctional signaling networks and is found in virtually all organisms, including single-cell organisms, humans, and all mammalian species tested. mTOR1 has very complex functions in the human cell, but to simplify matters, mTOR1 can be seen as a signaling molecule that encourages cellular growth, proliferation, and energy production when energy resources (i.e. nutrients such as sugars, fats, proteins) are abundant. Alternatively, when nutrients are low (such as in fasting, starvation, etc), mTOR1 is inhibited allowing cell survival through a process called autophagy. Autography, literally “self-eating”, is a highly conserved and fundamental means of cell survival. At times of cellular stress or energy depletion, autography leads to degradation of damaged or expendable cytoplasmic macromolecules and cellular structures that are then “recycled” to create new energy sources and cellular components. It is this inhibition of mTOR1 and the subsequent process of autophagy that promotes cell longevity and reduces the incidences of cell inflammation, cell dysfunction, and cancers. Rapamycin, in binding to mTOR1, effectively inhibits its activity and allows for the crucial activities of cell repair and recycling which are promoted through autophagy. The inhibition of mTOR1 not only improves the health of the aging cell, it also promotes the removal of diseased pro-inflammatory and pro-cancer cells.
What evidence do we have to support the role of Rapamycin in longevity?
Fortunately, the effect of rapamycin on longevity has been demonstrated repeatedly in species as simple as worms to as complex as rodent models. In one particular landmark study, Mice of advanced age (600 days old or the equivalent to late-middle life for humans) were treated with food fortified with Rapamycin or Placebo. Those middle age mice treated with Rapamycin saw an increase in lifespan of 9% in males and 14% in females. In humans, this would approximate a lifespan increase of 8-12 years! A summary of the effects of Rapamycin on survival in other mice disease models includes favorable longevity extension for a large number of cancers, immunodeficiency, lupus, Marfan syndrome, tuberous sclerosis and mixed results for mitochondrial disease and progeria.The bottom line is that mTOR1 is a cell-signaling compound that is found in most eukaryotic cells and appears to have similar functions in different species. It is the ubiquitous role of inhibiting mTOR1 in various species that leads us to believe that similar effects are likely to be seen in humans.
What data do we have on Rapamycin use in humans?
Unfortunately to date there is no long-term studies looking at the role of rapamcyin in longevity in Humans. The absence of such research is partly because Rapamycin's role in longevity is a fairly recent development and partly because studies looking at human longevity are technically difficult due to the long lifespan of humans relative to other animals.
Most of the data we have on Rapamycin use in humans is based on trials of patients using rapamycin for organ transplants. When added to other immunosuppressants, rapamycin appears to have a preventive effect against cancer development in such patients.
A more recent 4-month pilot study in health adults age 75-90 years showed that oral rapamycin was well tolerated without only mild side effects and no serious adverse reactions.
Currently, there are a number of Phase II clinical trials on rapamycin and longevity in healthy adults that are currently being conducted. These trials are focusing on the safety of rapamycin in addition to its role in reducing biomarkers of aging. Biomarkers of aging are surrogate markers of aging which range from elevated blood pressure measurements (which tend to increase with age) to molecular changes at the level of the genome/epigenome. While there is no gold standard biomarker for aging, if these trials can demonstrate a consistent reduction in the biomarkers of aging, we will be one step closer to determining the role of rapamycin in promoting longevity
How is Rapamycin taken for longevity?
Current research protocols in Rapamycin’s role of longevity in humans has focused on once weekly dosing (far lower than the standard daily dosing of rapamycin used in organ transplants). The rationale for once weekly dosing is to selectively inhibit mTOR1 while having limited inhibition of mTOR2 (which has adverse effects on glycemic regulation, immunological function and appears to shorten lifespan in male mice) Most human dosing protocols use dose range anywhere from 5-10 mg weekly.
Is rapamycin safe?
Rapamycin, in its use as a daily transplant rejection medicine, has a relatively benign safety profile. Given rapamycin’s role as an immunomodulator (and in some cases an immunosuppressant), daily use does carry the concern for increased susceptibility to bacterial infections. Daily use can also be associated with increased blood pressure, worsening cholesterol, worsening blood sugar, and reduced kidney function. Fortunately, in the studies which have looked at patients on weekly dosing (for longevity), the only significant difference between the rapamycin group and the placebo group was an increase in the incidence of mouth ulcers. Of course, given the relatively new use of Rapamycin in the promotion of longevity, it is recommended that any one on such a protocol be followed by a trained medical professional and undergo regular clinic follow ups and lab testing.
Is it safe to take rapamycin with other medications?
Rapamycin does have certain drug interactions which will be monitored by your Valuemed team. If you are taking any new medications or supplements, it is important that you disclose this information to your physician.
How Do I know if Rapamycin is right for me?
Given that Rapamycin for longevity is on the frontier of anti-aging medicine, there has been growing interest in taking rapamycin for longevity. Fortunately, Rapamycin therapy for longevity is an option for most adult patients who are interested in anti-aging medicine. There are certain patients, however, who should avoid Rapamycin therapy. This includes:
- Pregnant patient
- Immunosuppressed patients
- Patient's with active cancer
- Patients with severe kidney or liver disease
- Transplant recipients (unless directed by their physician).
To determine if you would be a good candidate for such therapy, please make an initial appointment with your Valuemed provider to learn more.
How do I know if rapamycin is working for me?
Currently there are no definitive tests to determine if Rapamycin is reducing an individuals rate of aging. At Valuemed, we do monitor our Rapamycin patients' blood work regularly to assess for any adverse reactions, however, there is no gold standard test to measure aging.
There is currently a great deal of interest in using epigenetic aging clocks to measure our rate of aging and how that rate of aging is impacted by either lifestyle changes, environmental exposures, or medications. If you are interested in learning more about these clocks and how they may be used to monitor the effects of your Rapamycin therapy, please feel free to discuss this matter with your Valuemed provider.
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