Gene Treatment in Mice Makes Old Liver Cells Young

Better 'waste disposal' could one day help treat human illnesses such as Alzheimer's, study says

By Ed Edelson
HealthDay Reporter

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MONDAY, Aug. 11 (HealthDay News) -- An experiment that improved the natural cellular garbage-disposal system in mice made old liver cells act young again. And the same rejuvenating effect might be possible one day in the brain and other body parts of humans, researchers report.

"We studied one of the systems that remove damaged proteins," said study leader Dr. Ana Maria Cuervo, an associate professor of developmental and molecular biology at Albert Einstein Medical College in New York City.

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This system handles about 30 percent of the cells' damaged proteins, escorting them to inner cell structures called lysosomes, where enzymes break the proteins down. Studies by Cuervo have shown that the disposal system becomes less efficient as cells grow older. They've also pinpointed the reason for the age-related decline -- a loss of receptors on the surface of the lysosomes that causes a buildup of damaged proteins in the cell.

For the study, Cuervo did some genetic engineering, creating mice with an extra gene for the lysosome receptors. The extra gene was added only to liver cells and was turned on only when the mice reached middle age. When the mice were examined at 22 to 26 months of their life -- equivalent to 80 years for a human -- "the liver cells were able to maintain the same level of activity as when they were young," Cuervo said. "They removed all damaged oxidized proteins."

To test whether improved protein clearance in liver cells helped overall liver function, Cuervo injected a muscle relaxant into very old mice who had the added gene. Those mice metabolized the relaxant as quickly as normal young mice.

The experiment was "a proof of principle," Cuervo said, and she is moving on to work with brain cells. She said she's working with an animal model of Parkinson's disease, "and we hopefully can prevent brain deterioration."

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