Starting Rapamycin Antiaging Human Trials

Rapamycin has been proven to extend the lifespan of mice, warms and yeast. is starting a large clinical trial named Participatory Evaluation (of) Aging (with) Rapamycin (for) Longevity Study, or PEARL, to see if the antiaging effects of Rapamycin apply to humans. This will be the first study to see if Rapamycin works as well in humans as it does in mice.

The PEARL trial will follow up to 200 participants over 12 months testing four different Rapamycin dosing regimens. It will be double-blind, randomized, placebo-controlled and registered with The principal investigator is Dr. James P Watson at UCLA, who was also a PI for the famous TRIIM trial.

Tests and measurements will be taken, both after 6 and 12 months. These will include autonomic health tests, blood tests, body composition tests, fecal microbiome testing, immune and inflammation health tests, methylation age clock testing and skeletal muscle tests.

A study from 2019 shows that while Rapamycin is somewhat similar to calorie restriction it has different effects in other ways.

The current data show that dietary restriction and rapamycin have different effects on many pathways and molecular processes. In addition, these interventions affect the lifespan of many genetically manipulated mouse models differently. In other words, while dietary restriction and rapamycin may have similar effects on some pathways and processes; overall, they affect many pathways/processes quite differently. Therefore, rapamycin is likely not a true dietary restriction mimetic. Rather dietary restriction and rapamycin appear to be increasing lifespan and retarding aging largely through different mechanisms/pathways, suggesting that a combination of dietary restriction and rapamycin will have a greater effect on lifespan than either manipulation alone.

Mikhail V. Blagosklonny wrote Rapamycin for longevity: opinion article in Aging Journal.

He said the following about rapamycin:
If used properly, rapamycin is not much more dangerous than ordinary aspirin. Aspirin, one of the most widely used nonprescription medications, may cause numerous side effects, including life threatening gastric bleeding. The manufacturer lists as possible side effects: ringing in ears, confusion, hallucinations, seizure, severe nausea, vomiting, bloody stools, coughing up blood, fever and swelling. Still, millions of people take aspirin daily to prevent cardiovascular disease and cancer. It was calculated that the benefits of aspirin are greater than their risks. I believe the benefits of the anti-aging effects of rapamycin/everolimus may even be greater.

Rapamycin known in the clinic as Rapamune or Sirolimus, was unlucky from the start, however. Twenty years ago, it was labeled an immunosuppressant and used to treat renal transplant patients. If rapamycin had been labeled an immunomodulator and anti-inflammatory drug instead, it would sound much more appealing now. At anti-aging doses, rapamycin “eliminates hyperimmunity rather than suppresses immunity” or, more figuratively, it “rejuvenates immunity”. This enables rapamycin and everolimus, a rapamycin analog, to act as immunostimulators, improving immunity in cancer patients and the elderly. For example, rapamycin reduces the risk of CMV infection in organ transplant patients, improves antipathogen and anticancer immunity in mice, prolongs lifespan in infection-prone mice and protects aged mice against pneumonia. Rapamycin also inhibits viral replication. As a noteworthy example, rapamycin inhibits replication of the 1918 flu virus (the deadliest flu virus in history) by 100-fold, and also protects against lethal infection with influenza virus when administered during vaccination. Still, as Dr. Allan Green advises, patients taking rapamycin should be carefully monitored for skin and subcutaneous bacterial infections, which should be treated with antibiotics.

Rapamycin and everolimus are FDA-approved drugs, safe for human use. Since 1999, rapamycin has been used by millions of patients with no unexpected problems. One may suggest that rapamycin/everolimus are safe enough for very sick patients, not for healthy people.

Rapamycin reduces the risk of cancer and can extend the lives of short-lived animals by 7-14%.

There is a separate antiaging trial from the TAME trial for the antiaging effects of Metformin.

SOURCES –, Aging journal, Afar
Written By Brian Wang,