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 , 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鈥檚 effects by activating SIRT1, a protein implicated in ageing. Experiments have led some to conclude that these drugs ramp up the protein鈥檚 activity, but the new studies suggest that those experiments suffered from errors.
鈥淚 think it鈥檚 a setback because there鈥檚 been a lot of optimism about these resveratrol-like compounds,鈥� says , 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.
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, a drug development firm based in Cambridge, Massachusetts, is hoping these and similar drugs will treat age-related disorders such as type聽2 diabetes and cancer, and has numerous . The company was bought by pharmaceutical giant GlaxoSmithKline (GSK) for $720聽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 in Thousand Oaks, California, and , 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 鈥� the opposite of what a Sirtris team . The Amgen team also conclude that resveratrol doesn鈥檛 activate SIRT1.
GSK questions the validity of the Pfizer team鈥檚 findings. The researchers 鈥渟et 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鈥�, a representative wrote in an email to New 杏吧原创.
Don鈥檛 give up yet
Even if resveratrol and the Sirtris compounds don鈥檛 combat ageing, this doesn鈥檛 make them worthless 鈥� 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鈥檛 seem to extend the lifespan of healthy rodents. 鈥淚t may be that resveratrol-like compounds are going to be therapeutically useful in people,鈥� Kaeberlein says.
If they aren鈥檛, 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: .
Last year, a group led by at the Jackson Laboratory in Bar Harbor, Maine, revealed that aged mice given rapamycin, a transplant drug lived 10聽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. 鈥淩ight now everybody and his uncle are trying to find something that acts like rapamycin.鈥�
Journal references: Pfizer test: ; Amgen:
