Can rapamycin reverse aging?

The quest to look young forever has gripped people for centuries.

Elixirs are renowned throughout history for their primary purpose of making people appear young – this fountain of youth, however, has proved elusive.

Rapamycin might be a good candidate for delaying the aging process. However, scientific evidence to support the claim that rapamycin can reverse aging is based on animal model studies and not on wide-scale and extensive clinical trials on humans. Despite the lack of human studies supporting the claim that it can reverse aging, this drug has proved promising in restoring youthfulness and delaying the aging process in mice and other animal studies. 

What is rapamycin? 

Rapamycin is a drug produced by the Streptomyces hygroscopicus, a bacterium abundantly found in soil. This product was first discovered in the soil of Eastern Island in 1972 and was named after Rapa Nui, Easter Island’s indigenous name. 

Rapamycin belongs to a group of antibiotics called macrolide, which includes roxithromycin, erythromycin, clarithromycin and azithromycin. This drug exhibits potent immunosuppressive and anti-tumour activities. 

What is the usage of rapamycin? 

Since it is a potent immunosuppressant, it has been used as an immunosuppressant drug for cancer patients. As an immunosuppressant, it is also commonly used in kidney transplant patients to prevent rejection. 

Apart from suppressing organ transplant rejection, it is also used to treat lymphangioleiomyomatosis, a rare lung disease. In addition, it is used as a coronary stent coat. 

While rapamycin has been used for several years as an immunosuppressant, it is only in recent years that its potential to increase lifespan has been discovered. In contrast to its effectiveness as an immunosuppressant in high doses, rapamycin can increase the lifespan of mice, yeasts and fruit flies. Interestingly, it can only increase lifespan if this drug is given in low doses. 

Can rapamycin increase lifespan? 

One of the relatively new benefits discovered for rapamycin includes its ability to increase lifespan. 

A study on mice [1] showed that rapamycin was effective in increasing the lifespan of the mice. The investigators of this study used mice that were 20 months old. This is roughly equivalent to the human life span of 60 years old. The mice were treated with low doses of rapamycin for three months and abruptly stopped treatment to examine the lifespan of these mice until they naturally died. 

In normal mice, the lifespan is only around 30 months. However, those treated with the drug lived for at least an average of two months. When translated to human lifespan, this is equivalent to an average increase of 6 years! In the study, one of the mice lived for three years and eight months. In human life, this is living up to 140 years old. 

In another study [2] that included fruit flies, results indicated that low doses of rapamycin could increase lifespan. Investigators of this study had fruit flies who were 30 days old. Rapamycin increased the lifespan of fruit flies treated at 30 days and 45 days old. Those in the experimental group outlived flies in the control group, suggesting that rapamycin can have the ability to prolong the lifespan of these flies. However, fruit flies who were 60 days old and were treated with rapamycin still died. Sixty-days-old fruit flies are regarded as positively geriatric! 

Administering rapamycin early in the life of the fruit flies appeared to have extended effects on its lifespan. The products were sustained even when the drug was stopped at 30 days. Results indicated that rapamycin’s effects are best seen when fruit flies are given the medication early in their life and stopped in middle age. 

What are the other benefits of rapamycin? 

Although initially used as an anti-cancer drug, rapamycin has been shown to have several benefits. These are some of the benefits recorded in animal model studies: 

  • Improvement of gut health: In the fruit fly study [2], rapamycin improved gut health by reducing the number of irregular patches in the fruit flies’ intestines. This is interesting as the drug might be promising in enhancing the overall gut health of animals. 
  • Treatment of cancer: Rapamycin has been used for several years as an anti-cancer drug. Giving in high doses can stop the spread or growth of cancer cells. However, when given at low doses, it has been shown to improve the immunity of cells.
  • Cardiovascular health: Patients with cardiovascular diseases with partially blocked arteries benefit from the insertion of coronary stents. These stents open blocked arteries and restore blood flow to the heart muscles. Rapamycin is an essential drug since it coats these stents, improving blood flow and health outcomes of the patients. 
  • Dementia: Patients with dementia suffer from a neurocognitive impairment that makes it difficult to remember things and do chores around the house. As the disease progresses, these patients become more dependent on their families and others to help them with daily household activities. 

A study [3] on mice revealed that rapamycin could potentially treat dementia. Here are some recorded effects of rapamycin on mice with dementia: 

  • Improvement of cognitive function 
  • Prevention of neuronal loss
  • Reduction of neurofibrillary tangles 
  • Reduction of amyloid-beta deposition and tau phosphorylation 
  • Restoration of cerebral blood flow 

Even when signs of dementia had begun to appear in the mice, treatment with rapamycin reduced these symptoms and delayed the progression of the disease. Importantly, memory loss was also prevented. 

Is it safe to take rapamycin? 

Currently, there have been no large clinical trials examining the effectiveness of rapamycin as an antiaging drug. However, for cancer patients treated with rapamycin and those who received organ transplants, some of the known side effects include the following: 

  • Swelling of the feet and hands 
  • Diarrhea or constipation 
  • Development of high blood pressure or hypertension 
  • Presence of fatigue and anaemia 
  • Weakened immune system 
  • Inflammation of the mouth or mouth sores 

Notably, these side effects were seen in immunosuppressed patients. It is unclear if the same side effects can be seen in otherwise healthy patients taking the drug to delay aging, but rapamycin remains a controlled drug, meaning it needs to be prescribed by a licensed physician.

What is the recommended dose for rapamycin? 

Current information on the appropriate drug dose is taken from patients who received this medication for organ transplants or cancer. 

1.2mg/day is recommended as safe for organ transplant donors. However, one study [4] showed that an intake of 2-5 mg/day dose of the drug is still safe and did not lead to adverse reactions or events. 

Who should not take rapamycin? 

Pregnant women and those breastfeeding should not take the medication as it is still unknown if this can affect the fetus or breastfeeding infants. Further, older patients who have kidney diseases or those with reduced kidney function should also not take the medication. 

Can I take rapamycin as an antiaging drug? 

Photograph: Master1305/Shutterstock

Although this drug is promising in delaying aging and prolonging lifespan in animal model studies, it is still being determined if the same effects can be seen in humans. To date, large clinical trials are still needed to verify the findings of animal model studies. Further, there is a general misconception that since rapamycin is an antidepressant drug, it might affect the immune system of individuals. However, it is safe in relatively low doses and can boost the immune system if given in low doses. 

Should I talk to my doctor if I plan to take rapamycin? 

It is always best to talk to your doctor if you plan to take drugs such as rapamycin. Since there are still no comprehensive studies investigating the effectiveness of this drug in prolonging lifespan or promoting longevity, caution must be advised. Always consult your doctor before taking any doses of rapamycin. 

References: 

[1] https://pubmed.ncbi.nlm.nih.gov/27549339/ 
[2] https://www.nature.com/articles/s43587-022-00278-w
[3] https://pubmed.ncbi.nlm.nih.gov/29351469/
[4] https://pubmed.ncbi.nlm.nih.gov/33277457/

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