Why Our ‘Most Promising’ Lifespan-Extending Drug Needs More Research

Rapamycin is considered by many to be one of our most promising lifespan-extending drug candidates. This compound has an interesting story. It was first identified as the natural product of a soil-dwelling bacterium on the island of Rapa Nui (Easter Island). For the bacterium, it serves as an anti-fungal agent, but it was soon found to be an immune system suppressant in humans, and has been used as such to prevent organ transplant rejection.

What does this have to do with ageing? Rapamycin also mimics the effects of calorie restriction (a sharp reduction in calorie intake without causing malnutrition), which has been shown to extend lifespan in animals and appears to have many health benefits in humans. Rapamycin achieves this primarily by inhibiting a ‘master regulator’ of cellular energy management called mTOR, which stands for mammalian Target Of Rapamycin. This has the effect of making the cell behave as though nutrients are scarce, acting to slow growth, conserve energy and repair damage.

Quite a few drugs have been shown to extend lifespan in animals, so what makes rapamycin one of the most promising? Firstly, rapamycin is one of few drugs that has been shown to consistently extend both average and maximum lifespan in large, well designed animal studies. In female mice (where the benefits of rapamycin are greater), rapamycin at sufficient doses extends both median lifespan (the age by which 50% of mice are dead) and P90 lifespan extension (the age by which 90% of mice are dead) by 20-25%.

Secondly, rapamycin has a well established safety profile in humans, having been used as an immune suppressant for many years. Furthermore, it doesn’t suppress the immune system at lower doses (in fact, it actually seems to enhance it). This means that while the evidence for human benefits are limited, some argue that the risks are sufficiently low that taking rapamycin for general health is a gamble that you are likely to win. Compare this to things like the peptides that are all the rage at the moment, or even some dietary supplements, for which neither the safety nor the efficacy has been well documented, and rapamycin starts to look quite appealing.

Rapamycin is a generic drug. This is a bit of a double-edged sword, because it means there is less monetary incentive for pharmaceutical companies to fund clinical trials to answer new questions. Academics have to secure their own funding, such as in the case of the PEARL trial that was crowdfunded by lifespan.io and found that low dose rapamycin was safe in healthy, elderly people with mixed benefits.

Now a new clinical trial of rapamycin, this time conducted by researchers at the University of Texas at San Antonio, is being planned. This trial will be conducted in phases and will attempt to answer important questions about dosing strategy. Animal studies suggest that higher doses of rapamycin produce greater lifespan extension, but in humans, immune suppression and elevated blood sugar start to emerge once doses become too high. However, because evidence for the effects of rapamycin in healthy humans is scarce, anyone taking rapamycin off-label for anti-ageing effects is engaging in guesswork when it comes to dosing. Last year, rapamycin made some headlines when longevity enthusiast and self-experimenter Bryan Johnson stopped taking the drug due to concerns over the side effects he was experiencing. Thus, while the safety profile of rapamyin for immune suppression is well established, taking any dose of rapamycin when healthy should still be treated as what it is: self-experimentation requiring expert medical supervision, with no guarantee that it will make you healthier or live longer.