Researchers have identified rapamycin as a promising anti-aging intervention that matches the lifespan-extending benefits of calorie restriction and intermittent fasting, according to the largest meta-analysis of its kind. The comprehensive study, conducted by scientists from the University of East Anglia and University of Glasgow, analyzed 167 studies across eight vertebrate species and found rapamycin consistently extended lifespans without requiring dietary modifications.
Meta-Analysis Reveals Consistent Anti-Aging Effects
The meta-analysis examined lifespan-extending therapies across primates, rodents, fish, and other vertebrates to compare rapamycin's effectiveness against traditional healthy aging methods. Dr. Zahida Sultanova from UEA's School of Biological Sciences explained the study's motivation: "Dietary restriction – for example through intermittent fasting or reduced calorie intake – has been the gold standard for living longer. But it's difficult for most of us to maintain long-term."
The research team found that dietary restriction extended lifespans across all eight vertebrate groups in the 167 studies. Crucially, rapamycin demonstrated equally consistent results, while metformin, another drug studied for anti-aging properties, showed less effectiveness. Rapamycin's healthy aging biomarkers remained consistent across both males and females.
Clinical Trial Confirms Safety in Healthy Adults
Supporting these findings, the PEARL trial represents the longest study to date exploring rapamycin's use for longevity in healthy aging adults. Led by researchers from AgelessRx, this randomized, double-blind, placebo-controlled study followed 114 participants aged 50 to 85 over 48 weeks.
Participants received either a placebo or 5 mg or 10 mg of compounded rapamycin once per week. The trial's primary endpoint measured changes in visceral fat, while secondary outcomes included lean muscle mass, blood markers, and quality-of-life assessments.
The study found that low-dose rapamycin was safe and well-tolerated, with serious side effects reported at similar rates across all groups. The most frequent minor issue among rapamycin users was mild gastrointestinal discomfort. Women taking 10 mg of rapamycin showed significant gains in lean muscle and reported reduced pain, while participants taking 5 mg weekly reported improvements in emotional well-being and general health.
Mechanism of Action and Clinical Potential
Rapamycin, also known as sirolimus, functions as an mTOR (mechanistic Target Of Rapamycin) inhibitor, regulating crucial biological functions like cell growth and repair. The drug signals mTOR to slow down and initiate cellular cleanup processes (autophagy), making cells better at responding to stress and preventing unchecked cell growth that can lead to damaged material buildup and trigger diseases like cancers and dementia.
Originally isolated from the Streptomyces hygroscopicus bacterium found in Easter Island soil samples in 1964, rapamycin gained FDA approval for preventing transplanted organ rejection and treating rare lung disease lymphangioleiomyomatosis and some rare cancers. While it doesn't reverse aging, it delays the biological aging process to promote healthy aging.
Implications for Longevity Research
Co-lead researcher Edward Ivimey-Cook from the University of Glasgow cautioned that "these findings don't suggest we should all start taking rapamycin, but they do strengthen the case for its further study in aging research and raise important questions about how we approach longevity therapeutics."
The researchers emphasized that current anti-aging interventions can prove challenging for many people, as long-term calorie-restricted diets and intermittent-fasting regimens are difficult to maintain. If medical treatment could achieve similar healthy-aging results regardless of diet, rapamycin's appeal becomes clear.
Dr. Sultanova noted that "our findings show that drug re-purposing is a promising approach to improving people's health and lifespan." The PEARL trial researchers concluded that "our findings provide evidence that these rapamycin regimens are well tolerated with minimal adverse effects when administered for at least one year within normative aging individuals."
While these findings are based on studies in non-human vertebrates and a single human trial, rapamycin is currently under investigation in additional human trials to further assess safety and efficacy for longevity applications.
