Rapamycin: Anti-Aging Benefits and Possible Side Effects

Rapamycin is getting more attention for its potential anti-aging benefits. It has been used to treat specific lung diseases, prevents organ-transplant rejection, and coat coronary stents. Additionally, it was shown to extend the lifespan of mice in 2009. Since then, researchers have been investigating the possibility of using rapamycin for longevity and treating age-related diseases in humans.

Key takeaways:
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    Rapamycin is most commonly used as an immunosuppressant to prevent organ rejection after kidney transplants.
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    Rapamycin's longevity effects are promising, partly because it seems likely to help prevent age-related diseases, such as Alzheimer's and some types of cancer.
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    Rapamycin anti-aging effects are still under investigation, but many scientists are excited about the possibilities after successful age-extension studies in mice and rats.

However, thus far, the promise of using rapamycin as a supplement has been offset by side effects associated with high doses. This article will explore how rapamycin works, its benefits, mechanisms, and potential for treating diseases and prolonging a healthy life.

What is rapamycin?

Rapamycin is a compound produced by a bacterium called Streptomyces hygroscopicus. It was first isolated in 1972 from a soil sample found on Easter Island. The compound's name comes from the island's native name, Rapa Nui. Rapamycin is also referred to as Sirolimus in clinics, and it's sold under the brand name Rapamune.

Rapamycin was initially used as an antifungal. However, it is most commonly used in clinics as an immunosuppressant to prevent organ rejection during transplant surgery. It's also used as an antiproliferative, meaning it can have the ability to inhibit cell growth, including the growth of malignant (cancerous) cells. The FDA approved the use of Rapamune for kidney transplant patients in 1999.

Researchers are still exploring the use of rapamycin for longevity, using it to either slow the aging process or prevent age-related diseases. However, it has been shown to prolong the lifespan of many species of mice, yeast, and fruit flies (Drosophila melanogaster).

Rapamycin mechanism of action

Rapamycin's immunosuppressive and antiproliferative properties come from its ability to inhibit the activation of B cells and T cells. It reduces these cells' sensitivity to interleukin-2 (IL-2), a molecule in the immune system that helps regulate white blood cells.

Rapamycin works by inhibiting the mechanistic target of rapamycin (mTOR). In humans, mTOR is a protein kinase encoded by the MTOR gene and plays a role in insulin, growth factor, and amino acid pathways; sensing oxygen, energy, levels, and cellular nutrients; regulating metabolism; and the function of the brain, muscles, liver, and tissues.

Dysregulated mTOR has been implicated in diseases like obesity, diabetes, cancers, autism spectrum disorders, Alzheimer's disease, lupus, and lymphoproliferative diseases, as well as shortened lifespans (in fruit flies, some worms, and yeast). That is why rapamycin's ability to inhibit mTOR is linked to preventing and treating these same conditions.

Benefits of rapamycin

Studies have been conducted for decades on rapamycin in dogs, worms, fruit flies, mice, and rats. The full extent of the beneficial effects of rapamycin is still being investigated in humans.

Rapamycin's anti-aging effects are a source of excitement among scientists and consumers alike. It remains to be seen whether rapamycin helps prevent the diseases associated with aging and improve quality of life or if it can extend the length of a human's life directly.

Currently, rapamycin is used in human medicine for:

  • Preventing organ-transplant rejection after surgery (as an immunosuppressant);
  • Treating some types of cancer (as an antiproliferative);
  • Treating cardiovascular disease (as a coating for heart stents used to treat blocked arteries).

Anti-aging effects

The use of rapamycin for anti-aging is likely most effective if administered to people before they develop age-related diseases so that they can increase both health and lifespan. However, it is not a cure-all but a supplement that could be used alongside a healthy lifestyle and diet.

Rapamycin's anti-aging effects are complex because scientists still don't know precisely what causes aging. A halt in cell division, a loss of stem cells, damaged DNA, and shortened telomeres all seem to play a role in both the degeneration of the body and in age-related diseases that cut lifespans short, like Alzheimer's.

Increases longevity

The role of rapamycin in longevity is related to its ability to enhance autophagy, a process that resolves damage to cellular organs and protects cells from stress.

When rapamycin inhibits mTOR, it appears to boost autophagy simultaneously. This, in turn, could delay the onset of the body's aging process and age-related diseases and give people a longer and healthier life. That's why some researchers believe we might be able to use rapamycin for longevity.

Treating cancer

Mammalian target of rapamycin (mTOR) encourages cell growth and proliferation, which affects the body's ability to remediate cellular damage through autophagy. This can lead to various diseases, including cancer (the uncontrolled growth of cells).

Inhibiting mTOR appears to halt tumor proliferation and induce tumor cell apoptosis (cell death) and angiogenesis (supplying tumors with the network of blood vessels they need to receive nutrients).

Rapamycin is used to treat certain cancers, and two rapamycin derivatives called temsirolimus and everolimus (aka "rapalogs") are FDA-approved to treat advanced kidney cancer.

Skin aging

Topical rapamycin cream is used to treat skin conditions, including vascular anomalies, facial angiofibroma, and psoriasis in children and young adults.

Mikhail V. Blagosklonny of Buffalo, NY's Roswell Park Cancer Institute, has been the leading proponent of using rapamycin for signs of skin aging (sun spots, wrinkles, and more). He has also pointed out that studies have shown topical rapamycin application can reduce sagging skin and photoaging and improve dermal volume on hands, thereby slowing the process of skin again. However, a topical rapamycin cream is not yet a cosmetic reality.

Rapamycin dosage

Right now, a rapamycin prescription is only available for organ transplant rejection prophylaxis and pulmonary lymphangioleiomyomatosis — a condition that causes the lungs to lose function— outside of studies or cardiac surgeries.

Age groupRapamycin dosage
Adults6 mg (first day), followed by 2 mg/day
Adults (high immunologic risk)15 mg (first day), followed by 5 mg/day
Children3 mg (first day), followed by 1 mg/day

Systemic treatment in adults typically involves a rapamycin dosage of 6 mg taken orally on day one (a loading dose), followed by 2 mg/day orally. Pediatric doses are about half of the adult rapamycin dosage. Those at high immunologic risk may be prescribed a loading dose of up to 15 mg and a daily dose of up to 5 mg.

Since neither rapamycin nor rapalogs are indicated for anti-aging, a customer would have to find a doctor willing to prescribe it off-label and pay for it out of pocket.

How to take rapamycin

For those taking rapamycin off-label — or importing it from foreign pharmacies — there are no instructions for use outside of a doctor's advice. For approved rapamycin users, the medication is typically taken orally in tablets.

Rapamycin tablets should not be split, crushed, or chewed; they should be swallowed whole. Patients unable to swallow a pill may be prescribed an oral solution. Rapamycin can be taken with or without food but should be taken consistently in one way or the other. Grape juice should be avoided while taking rapamycin.

While researchers have used rapamycin cream topically in trials on skin aging, it is not available to the public since the risks have yet to be fully assessed.

Possible side effects of rapamycin

Because rapamycin suppresses the immune system, it should only be administered under a doctor's orders. In some cases, there are concerns that the same pathways the compound uses to inhibit mTOR could also cause disease. However, not all scientists agree on the potential Rapamycin side effects.

Possible side effects of rapamycin can be severe and include:

  • Fever;
  • Cold symptoms (such as a stuffy nose or sore throat);
  • Mouth sores;
  • Nausea;
  • Diarrhea;
  • Stomach pain;
  • Muscle aches;
  • Chest pain;
  • Headache;
  • Dizziness.

If rapamycin is prescribed for anti-aging, it is likely to be used at low doses and perhaps intermittently throughout one's lifespan to avoid side effects.

How rapamycin triggers autophagy?

Rapamycin's primary benefit is in triggering autophagy in a variety of cells. It does this mainly by inhibiting mTOR-induced cell proliferation.

Depending on the model system being targeted, rapamycin can induce autophagy using different mechanisms. Sometimes it needs to be combined with an inhibitor to sensitize the cells. In other cases, rapamycin may require the use of in vivo reporter cells. Rapamycin treatment is tailored for specifically-targeted cells by a physician to ensure the molecular mechanisms at play are properly activated.

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