The two faces of rapamycin – why a life-extending drug also increases risk of diabetes

A plaque on Easter Island commemorates the discovery of rapamycin

You don’t have to go far to find supposed ways of delaying the ageing process, from oddball diets to special supplements. But these fountains of youth are all hype and no substance. For now, there are only a few methods that have consistently extended the lives of mammals. Eating less – formally known as “caloric restriction” – is one of these. Rapamycin, a drug originally found in Easter Island bacteria, is another. It can lengthen the lives of old mice by 9 to 14 per cent, and it boosts longevity in flies and yeast too.

But rapamycin has its downsides. For a start, it strongly suppresses the immune system. That is why it is currently given to people who receive new organs, to stop them from rejecting their transplants. Rapamycin can also increase the risk of diabetes. In mice, rats and humans, the drug weakens the ability to stabilise levels of sugar in the blood. Individuals who take it for a long time become resistant to insulin, and intolerant to sugar.

You’d expect the opposite. Longer-lived animals ought to be better at dealing with sugar, and less likely to suffer from insulin resistance. Indeed, that’s what you see in individuals that cut down on calories. So why does rapamycin behave so paradoxically?