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Why has rapamycin gained such a following among longevity enthusiasts?

March 21, 2024

Your patients may be hearing more in media reports about rapamycin’s promise as a longevity drug; indeed, some researchers have dubbed the current interest in this drug as “a gold rush” in longevity medicine. (Gilbert, 2024)

Rapamycin, also known as sirolimus, is an mTOR inhibitor that was approved in the FDA in 1999 for kidney transplant rejection prophylaxis.

Although rapamycin is not approved by the FDA as a life-extension drug, it's increasingly being prescribed off-label—typically at a 5-mg/week low, intermittent dose—as a potential life-extension therapy based on improvements in health and lifespan seen in animal trials and current human studies. Preclinical studies have shown that rapamycin extends lifespan and healthspan metrics in yeast, invertebrates, and rodents. (Kaeberlin, 2023)

More than 24 medical practices currently prescribe rapamycin as an anti-aging treatment, according to a Washington Post review, and telehealth companies are bringing it to thousands of patients nationally. (Gilbert, 2024)

Longevity medicine practitioners like Peter Attia and American entrepreneur Bryan Johnson, who have amassed large followings on social media have also ignited the buzz about rapamycin.

Approximately 20,000 people visit the San Francisco-based Rapamycin News website each month. The site is home to a group of people taking the drug for its purported anti-aging properties. In this forum, users share their personal experiences and results with rapamycin and other anti-aging drugs.

Rapamycin users are not necessarily consulting their physicians. Approximately 20% of rapamycin users in a 2023 survey published in Geroscience reported taking rapamycin without the supervision of a physician. According to study authors: "Unsupervised use of prescription medications appears to be common within the biohacking community, based on comments found in multiple online forums, and is unlikely to be unique to rapamycin." (Kaeberlin, 2023)

Although prices vary widely, the generic availability of the drug means it's generally inexpensive: Some online purveyors offer a typical dose for about $10 a week or less.

Despite the excitement surrounding the drug, it is unlikely that the FDA will ever approve it for longevity as the agency doesn’t consider aging to be a disease. And because of rapamycin’s generic status, the rate of research has been gradual. There's little financial incentive to run expensive clinical trials to test it for age-related afflictions.

How does it work?

Rapamycin is said to modify the mammalian target of rapamycin (mTOR) that regulates cell proliferation, autophagy, and apoptosis by participating in multiple signaling pathways in the body. This mTOR signaling pathway is implicated in an increasing number of pathological conditions, including cancer, arthritis, insulin resistance, osteoporosis, and other diseases.

What's the evidence for it?

Some physicians and researchers believe that if taken intermittently and in low doses, rapamycin can increase human life span the way it has in animal trials. Thus far, however, there is limited data available on side effects or efficacy associated with use of rapamycin in this context. (Kaeberlein, 2024)

Three studies are consistently cited in media reports about rapamycin:

• A study published in Nature in 2009 found that rapamycin extended the lives of elderly mice by as much as 14%, the first time a drug had been shown to help a mammal live longer. (Harrison, 2009)
• An RCT published in Science Translational Medicine in 2014 found that older adults who took a rapamycin-like drug (RAD001) had an enhanced response to the flu vaccine by about 20% at doses that were relatively well tolerated. RAD001 also reduced the percentage of CD4 and CD8 T lymphocytes expressing the programmed death-1 (PD-1) receptor, which inhibits T cell signaling and is more highly expressed with age. These results raised the possibility that mTOR inhibition may have beneficial effects on immunosenescence (the decline in immune function during aging). (Mannick, 2024)
• In a 2023 survey published in Geroscience involving 333 people who used rapamycin off label, researchers found that they generally reported better quality of life and good health status since starting the drug. Ratios of greater than 3:1 in agreement were observed for self-reported improvements in health, happiness, brain function, feelings of youthfulness, confidence, calmness, anxiety, and generalized aches and pains. Among survey respondents, rapamycin users were on average slightly older than non-users for both men (9 years) and women (6 years). Rapamycin users reported consuming more alcohol than non-users, and a greater percentage of rapamycin users were male (78% male) compared to non-users (63% male). Compared with a cohort that didn’t take the drug, rapamycin had a statistically higher incidence of mouth sores. (Kaeberlein, 2024)

However, doctors also caution that no one knows what the optimal dose might be for humans. Some studies suggest that taking certain quantities of rapamycin can lead to reproductive harm and insulin resistance as well as an increased susceptibility to infection. (Gilbert, 2024)

“It is a drug that I think can be taken safely under certain conditions but has enough of a side effect profile that I’m not interested in taking it for sake of increasing life span at this time,” Andrew Huberman, a neuroscientist with a large social media following, said on a podcast in October. (Gilbert, 2024)

Sources:

Gilbert, Daniel. (2024, March 15). The Washington Post. How a cheap, generic drug became a darling of longevity enthusiasts. https://www.washingtonpost.com/business/2024/03/15/rapamycin-longevity-drug/

Kaeberlein T, et al. (2023, May 16). Geroscience. Evaluation of off-label rapamycin to promote healthspan in 333 adults. https://pubmed.ncbi.nlm.nih.gov/37191826/

Harrison DE, et al. (2009, July 16). Nature. Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. https://pubmed.ncbi.nlm.nih.gov/19587680/

Mannick JB, et al. (2014, December 14). Sci Transl Med. mTOR inhibition improves immune function in the elderly. https://pubmed.ncbi.nlm.nih.gov/25540326/