Scientists stop the ageing process

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Monday, 11 August 2008
ABC/AFP
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Clean bill of health: Scientists have shown that clearing damaged protein from the liver helps stop age decline in the organ (Source: iStockphoto)

Scientists have stopped the ageing process in an entire organ for the first time, a study released today says.

Published in today's online edition of Nature Medicine, researchers at the Albert Einstein College of Medicine at Yeshiva University in New York City also say the older organs function as well as they did when the host animal was younger.

The researchers, led by Associate Professor Ana Maria Cuervo, blocked the ageing process in mice livers by stopping the build-up of harmful proteins inside the organ's cells.

As people age their cells become less efficient at getting rid of damaged protein resulting in a build-up of toxic material that is especially pronounced in Alzheimer's, Parkinson's and other neurodegenerative disorders.

The researchers say the findings suggest that therapies for boosting protein clearance might help stave off some of the declines in function that accompanies old age.

In experiments, livers in genetically modified mice 22 to 26 months old, the equivalent of octogenarians in human years, cleaned blood as efficiently as those in animals a quarter their age.

By contrast, the livers of normal mice in a control group began to fail.

The benefits of restoring the cleaning mechanisms found inside all cells could extend far beyond a single organ, says Cuervo.

"Our findings are particularly relevant for neurodegenerative disorders such as Parkinson's and Alzheimer's," she says.

'Misbehaving proteins'
"Many of these diseases are due to 'misbehaving' or damaged proteins that accumulate in neurons. By preventing this decline in protein clearance, we may be able to keep these people free of symptoms for a longer time."

If the body's ability to dispose of cell debris within the cell were enhanced across a wider range of tissues, she says, it could extend life as well.

In healthy organisms, a surveillance system inside cells called chaperone-mediated autophagy (CMA) locates, digests and destroys damaged proteins.

Specialised molecules, the "chaperones", ferry the harmful material to membrane-bound sacs of enzymes within the cells known as lysosomes.

Once the cargo has been "docked", a receptor molecule transfers the protein into the sac, where it is rapidly digested.

With age, these receptors stop working as well, resulting in a dangerous build-up of faulty proteins that has been linked, in the liver, to insulin resistance as well as the inability to metabolise sugar, fats or alcohol.

The same breakdown of the cell's cleaning machinery can also impair the liver's ability to remove the toxic build-up of drugs at a stage in life when medication is often part of daily diet.

In genetically modified mice, Cuervo compensated for the loss of the receptors in the animals by adding extra copies.

"That was enough to maintain a clean liver and to prove that if you keep your cells clean they work better," she says.

Settles debate
The study goes a long way towards settling a sharp debate in the field of ageing research.

Leading Australian ageing researcher David le Couteur, Professor of Geriatric Medicine at the University of Sydney, says the paper is a major breakthrough.

"She has single-handedly shown that lysosome function is a crucial part of the ageing process," he says.

Cuervo has also shown, he says, the critical role the lysosomal receptor molecules play in keeping the liver clean of damaged proteins.

While her paper does not show increased survival rates among the mice, le Couteur, who has advised her recently on the research, says Cuervo does have data on improved survival rates which she intends to publish.

He also says she is now working with pharmaceutical companies to identify drugs that will turn the receptors on, or make them more active.

Cuervo believes maintaining efficient protein clearance may improve longevity and function in all the body's tissues.

It is also possible that the same kind of "cellular clearance" can be achieved through diet, she says.

Research over the past decade has shown that restricted calorie intake in animals, including mammals, significantly enhances longevity.

"My ideal intervention in the future would be a better diet rather than a pill," she says.

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