Two off-patent molecules have attracted attention as potential chemical alternatives to calorie restriction for extending lifespan: rapamycin, an immunosuppressant used to prevent rejection of transplanted kidneys, and metformin, an anti-diabetes drug. Both inhibit the mTOR pathway (mTOR stands for "mechanistic target of rapamycin"), whose overactivation in old age is associated with hallmarks of ageing such as inflammation. Fasting suppresses mTOR activity too, promoting autophagy—a process in which cells clear out accumulated crud—which is reckoned to be lifespan-enhancing.
Experiments on species from nematode worms to rhesus monkeys show that near-starvation prolongs lifespan. A meta-analysis published in Aging Cell in June 2025 by Edward Ivimey-Cook of Glasgow University and colleagues gathered all available vertebrate-trial evidence: 167 studies on eight species, ranging from fish to monkeys. It found that calorie restriction works, as does rapamycin (to roughly the same extent), but that metformin does not extend lifespan in animals.
Being off-patent means both drugs are cheap, but also that commercial sponsors for human trials are hard to find. The Targeting Ageing with Metformin (TAME) trial, sponsored by the American Federation for Aging Research and approved by the Food and Drug Administration in 2015, has struggled to find funding. The PEARL (Participatory Evaluation of Ageing with Rapamycin for Longevity) trial began in July 2020 but found no strong evidence that rapamycin worked in humans.
Rapamycin's known side-effects include abnormal lipid and glucose levels, elevated heart rate and increased risk of skin infection.
So live that you wouldn't be ashamed to sell the family parrot to the town gossip.