GM mice live longer and give hope for anti-aging treatments

May 8 2005

U.S. scientists have produced genetically modified mice that live 20 per cent longer than normal and may have possibly discovered an approach to extending the human lifespan.

The mouse was genetically modified to produce more of an antioxidant protein that limits tissue damage which is caused by highly reactive chemicals called free radicals and the process could possibly be exploited to fight the ageing process in people.

According to the scientists the research suggests that drugs that protect the body against free-radical damage could control age-related conditions such as heart disease and help people to live substantially longer. The research also indicates that stimulating the body’s own production of antioxidants is likely to be more effective than using drugs, vitamins or other supplements with similar properties.

The benefits of a natural antioxidant enzyme,catalase, were seen only in mice that made extra quantities in specialised parts of their cells. This suggests that increased production needs to be precisely targeted for maximum effect.

Removing free radicals at the source appears to be the most promising way forward for anti-ageing medicine says Peter Rabinovitch, Professor of Pathology at the University of Washington School of Medicine in Seattle, who led the research.

Rabinovitch says the study supports the free-radical theory of ageing, and shows the significance of free radicals, and of reactive oxygen species in particular, in the ageing process.

He says the focus used to be on specific age-related diseases, because it was believed that the ageing process itself could not be affected, but scientists are now realising that by intervening in the underlying ageing process, they may be able to produce very significant increases in ‘healthspan’, or healthy lifespan.”

Two methods revealed in previous research that extend the lifespan of mice, are not practical for human use. Mice that are fed diets that border on starvation rations live substantially longer, and so do rodents that lack a genetic growth factor.

The first approach is not suitable for people because it would be impossible to follow for long periods, and the second has the side-effect of dwarfism.

Consequently research into ageing has focused more and more on the activity of free radicals and antioxidants, which are widely thought to play a critical part in the tissue damage that accumulates as organisms age.

In the new study the team sought to analyse the effects of catalase, an enzyme made by cells that helps to convert hydrogen peroxide into water and oxygen. Hydrogen peroxide is a waste product of metabolism that is often the precursor of free radicals, particularly reactive forms of oxygen, that can damage cells. This cellular damage itself leads to the production of more free radicals, creating a vicious circle of age-related decline.

The new study is published in the current edition of journal Science.