Efforts to slow the march of old age with a pill have been dealt a blow. Drugs that might treat disease by tampering with the biology of ageing are being tested, but new research questions whether they work as thought.

The compounds include resveratrol, a much-touted component of red wine that is thought to prevent the cellular damage that underlies ageing. Also under test are several chemicals intended to mimic resveratrol’s effects by activating SIRT1, a protein implicated in ageing. Experiments have led some to conclude that these drugs ramp up the protein’s activity, but the new studies suggest that those experiments suffered from errors.

“I think it’s a setback because there’s been a lot of optimism about these resveratrol-like compounds,” says Matt Kaeberlein, a biochemist at the University of Washington in Seattle who was not involved in either study and has no link with any company developing anti-ageing drugs.

Sirtris, a drug development firm based in Cambridge, Massachusetts, is hoping these and similar drugs will treat age-related disorders such as type 2 diabetes and cancer, and has numerous clinical trials already under way. The company was bought by pharmaceutical giant GlaxoSmithKline (GSK) for $720 million in 2008.


Bone of contention

The bone of contention in the new studies is a laboratory test meant to measure how far a drug boosts activity of SIRT1. Separate teams led by researchers at the drugs companies Amgen in Thousand Oaks, California, and Pfizer in Groton, Connecticut, contend that tests linking resveratrol to certain aspects of longevity turned up false positives.

As part of its own quest for anti-ageing drugs, the Pfizer team tested resveratrol and three Sirtris compounds using several more sensitive methods, and none of the compounds worked as expected. Furthermore, the drugs seemed to have unintended side effects that could undermine their usefulness to humans.

One of the most promising of the resveratrol-like drugs did not improve the health of mice fed a high-fat diet – the opposite of what a Sirtris team reported in 2007. The Amgen team also conclude that resveratrol doesn’t activate SIRT1.

GSK questions the validity of the Pfizer team’s findings. The researchers “set out to prove a negative and fall short of achieving that objective while adding little scientific insight to a complicated and emerging area of biology”, a representative wrote in an email to New Scientist.

Don’t give up yet

Even if resveratrol and the Sirtris compounds don’t combat ageing, this doesn’t make them worthless – far from it, Kaeberlein and others say.

It is already known that high doses of resveratrol can limit the toll of a high-fat diet on mice, although the compound doesn’t seem to extend the lifespan of healthy rodents. “It may be that resveratrol-like compounds are going to be therapeutically useful in people,” Kaeberlein says.

If they aren’t, Kaeberlein worries that enthusiasm and investment in longevity-boosting drugs could dry up. That would be a shame, he says, given the promise of another age-hacking drug: rapamycin.

Last year, a group led by David Harrison at the Jackson Laboratory in Bar Harbor, Maine, revealed that aged mice given rapamycin, a transplant drug lived 10 per cent longer than other mice.

Rapamycin, Harrison says, blocks a pathway called TOR that responds to nutrients in the environment which may be fundamental to ageing, and a furious search is under way to find chemicals that work in a similar way without dampening the immune system. “Right now everybody and his uncle are trying to find something that acts like rapamycin.”

Journal references: Pfizer test: The Journal of Biological Chemistry, DOI: 10.1074/jbc.m109.088682; Amgen: Chemical Biology & Drug Design, DOI: 10.1111/j.1747-0285.2009.00901.x