Drug makes Methuselah mice

2009-07-08 22:09

Paris - A compound found in the soil of Easter Island stunningly boosts the lifespan of mice, enabling some to live more than 100 years old in human terms, researchers reported on Wednesday.

The remarkable molecule, a bacterial by-product discovered in a sample taken from the remote Pacific archipelago in the 1970s, is called rapamycin, after the island's Polynesian name of Rapa Nui.

Rapamycin first came to light because of its qualities as a fungus fighter.

It was later used to prevent organ rejection in transplant patients and then became incorporated into "stents" - implants used to keep arteries open in patients with coronary disease. It is now in clinical trials for cancer treatment.

Massively boost human life expectancy

The latest step in this remarkable odyssey is the vision that rapamycin, or something like it, may one day massively boost human life expectancy.

"I've been in ageing research for 35 years and there have been many so-called anti-ageing interventions over those years that were never successful," said Arlan Richardson, director of the Barshop Institute, one of three centres that carried out the experiments.

"I never thought we could find an anti-ageing pill for people in my lifetime. However, rapamycin shows a great deal of promise to do just that."

Intrigued by findings that suggest rapamycin inhibits an enzyme linked to ageing in invertebrates, the researchers decided to add the drug to the diet of older mice.

The rodents were 20 months old at the time, which in human terms is equivalent to around 60 years of age.

Female mice with rapamycin added to their food lived 13% longer on average compared with non-rapamycin counterparts. Males which were fed the drug gained 9% in their lifetime.

Females lived longer than males

The change was even more striking among the 10% of mice that lived longest. Within this group, rapamycin females lived 38% longer and rapamycin males 28% longer than non-rapamycin counterparts.

Rapamycin may retard ageing processes or the onset of cancer but has no impact on the causes of death itself, the study adds.

The project, reported in the British science journal Nature, is part of a test programme under the US National Institute on Ageing (NIA), which is looking for drugs that will help people remain healthy and active throughout their lives.

Previous work on rapamycin longevity was carried out on yeast, worms and flies. This study is the first to show it also appears to work on mammals.

Scientists have already found that by keeping mice skinny by restricting their diet, they could make the rodents live longer. The theory behind rapamycin is that it works on the same molecular mechanisms as calorie restriction.

'Totally unexpected'

Initially, the US researchers hoped to start giving rapamycin to mice from four months of age.

But the project was hit by delays in formulating the drug so that it could enter the specially-bred animals' bloodstream more effectively.

As a result, the experiment was not started until the mice were 20 months old, but the team decided to press ahead anyway.

"Most reports indicate that calorie restriction doesn't work when implemented in old animals," said Richardson.

"The fact that rapamycin increases lifespan in relatively old mice was totally unexpected."

In a commentary also published by Nature, University of Washington biochemists Matt Kaeberlein and Brian Kennedy cautioned middle-aged people against rushing to take rapamycin, given that the drug is known to suppress the immune system, which fights invading microbes.

Despite the rush of optimism sparked by rapamycin, "extending human lifespan with a pill remains the purview of science-fiction writers for now," they said.

- SAPA