NEWS: Gene defect slows aging in mice

Patrick Wilken (patrickw@cs.monash.edu.au)
Fri, 19 Nov 1999 10:02:50 +1100

GENE DEFECT FIGHTS AGEING
Thursday, November 18, 1999 Published at 10:39 GMT http://news.bbc.co.uk/hi/english/sci/tech/newsid_525000/525209.stm

Italian researchers have shown how a defective gene in mammals, including humans, can lead to a longer lifespan.

They bred mice that could not make a particular protein in their bodies and found the animals lived a third longer than normal rodents.

Professor Leonard Guarente, at the Massachusetts Institute of Technology, US told the BBC: "It's really the first time that anybody has intervened to extend the lifespan of a mammal without extracting some cost."

Lack of food, for example, can extend lifespan, but only by making the animals much smaller.

Commenting on the work published in the journal Nature, he added that the work held "if not the fountain of youth, more than a trickle of hope."

Many scientists around the world would like to know more about what controls longevity, not least because it might open up new ways to tackle cancer in which cells refuse to die.

But it is already clear many different processes are involved and the prospect of humans being able to live substantially longer lives remains some way off. Professor Guarante believes 10 years of research is needed before any drugs might result from this type of research.

The experimental mice used by a team led by Pier Giuseppe Pelicci of the European Institute of Oncology in Milan lacked a vital gene.

This protein, known as p66shc, is involved in the management of what is known as oxidative stress.

This is the damage cells suffer when exposed to certain oxidising agents, such as hydrogen peroxide and ultraviolet light. Oxidative damage is thought to be inextricably linked to the ageing process in all forms of animal life.

But quite why mice that cannot make p66shc should live a third longer than normal mice is not clear.

The Italian team suggest a cell repair mechanism triggered by oxidative stress is normally kept switched off by the protein.

The presence of an oxidative agent is thought to alter p66shc chemically in such a way that the brake comes off, and the repair system moves into action.

In mice with the defective gene, it is possible the brake is permanently disengaged, so the repair pathway is always open.

In other words, p66shc-deficient mice live longer because their repair mechanism works overtime.

It is also possible the action of an oxidative agent on p66shc triggers a suicide response in badly damaged cells. Apoptosis, or cell suicide, is one method animals use to protect themselves against cancer.

Past research indicates mutations in mice that lead to increased lifespan are connected with smaller size or reduced fertility. But in this study, no such defects have yet been identified.

But the team warn that their results should be treated with some caution as they pertain to only one strain of mouse, and the effects may not be reproducible in others.

Further work on p66shc is planned.

Back to top | BBC News Home | BBC Homepage | ©