Scientists have known that eating less can help animals live longer. But giving up foodโor at least some of itโis easier said than done. So researchers have turned to the next best thing: finding drugs that could trick the body into thinking it’s on a diet, without the hunger pangs.
Two such drugs have emerged as frontrunners: rapamycin, an immunosuppressant with roots in a soil sample from Easter Island, and metformin, a widely used diabetes drug that comes from the French lilac plant.
In a recent large-scale study, researchersโincluding myselfโcompared the effects of these drugs with the tried-and-tested method of calorie restriction. We reviewed over 160 studies covering eight animal species, from fish to primates. The findings? Rapamycin came close to matching the lifespan-extending effects of eating less. Metformin didnโt.
The original anti-aging hack
The idea that less food equals more life isnโt new. In the 1930s, lab rats placed on calorie-restricted diets lived longer than their well-fed peers. That discovery kicked off nearly a century of research into how nutritionโand deprivationโaffects aging.
The theory is that when the body senses food scarcity, it shifts into a maintenance mode. Cells stop dividing and start repairing. Metabolism slows. Damage control kicks in. And the aging process, it seems, also slows down.
But permanent dietary restriction is tough to sustain and, when taken too far, can even backfire. Thatโs why scientists have been asking: can we get the same benefits without the hunger?
Enter rapamycin and metformin
Rapamycin was first discovered in the 1970s from microbes in Easter Island soil. Today, itโs used to prevent organ rejection in transplant patients. It works by blocking a protein called mTOR, a master regulator that tells cells when nutrients are available.
Metformin, meanwhile, has been used for decades to manage blood sugar in people with type 2 diabetes. It also plays a role in how the body senses energy and regulates metabolism, making it a candidate for aging research.
Because both drugs interact with nutrient-sensing pathways in the body, researchers hoped they could mimic the life-extending effects of a calorie-restricted diet.
We put that theory to the test by examining thousands of published studies and narrowing them down to 167 with reliable data on survival and study design. Our goal was to see which strategyโeating less, taking rapamycin, or taking metforminโbest extended lifespan.
The verdict
The results were clear: calorie restriction remains the most consistent method for extending life across species. Rapamycin was a strong second. Metformin didnโt show a clear benefit.
Whatโs more, the life-extending effects of eating less appeared consistent across both male and female animals, and across different forms of restrictionโfrom simply eating smaller portions to intermittent fasting.
So where does that leave rapamycin?
A promising but cautious path
Rapamycin is now one of the most promising candidates in the search for anti-aging therapies. If aging is the biggest risk factor for chronic diseases like cancer, diabetes, and dementia, then slowing it down could mean not just longer lifeโbut a healthier one.
But there are caveats.
Some studies in our review showed that both calorie restriction and rapamycin reduced lifespan, depending on how the experiments were done. Most of the evidence also comes from mice and ratsโnot humans. And rapamycinโs known side effects include immune suppression and potential impacts on fertility.
Thatโs why researchers are now experimenting with low, intermittent doses of the drug to see if itโs possible to keep the benefits while avoiding the risks.
Early human trials are encouraging. Participants on small doses of rapamycin are showing improvements in markers linked to โhealthspanโโthe number of years we live in good health. A major trial for metformin is still underway, with results expected in a few years.
So should you take rapamycin?
Not yet. Rapamycin is still far from being an over-the-counter fountain of youth. But its storyโfrom a remote Pacific island to the cutting edge of anti-aging scienceโoffers a powerful insight: sometimes, targeting a single cellular switch is enough to reshape how the body ages.
The challenge now is to develop safe, affordable therapies that help people live not just longer, but betterโwithout giving up the joy of a good meal, or the occasional slice of chocolate cake.
