Gene Treatment in Mice Makes Old Liver Cells Young

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By Ed Edelson
HealthDay Reporter

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.

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."

Most people who develop Parkinson's disease or Alzheimer's disease are born with a mutation that gives rise to defective proteins late in life, Cuervo said. Improving the cellular protein disposal systems in brain cells might delay the onset of the conditions, she said.

Genentic engineering might not be needed to achieve the anti-aging goal in humans, Cuervo said. "As we understand why this system decreases with aging, we are trying to identify compounds that do the same thing," she said. "Also, we are looking at dietary manipulation. Some modifications in the diet might do the same thing."

The findings were published Aug. 10 in the online issue of the journal Nature Medicine.

Dr. Ronald Klatz, president of the American Academy of Anti-Aging Medicine, called the new study "another piece of evidence supporting the contention that aging is a reversible condition. We can not only slow aging, but also reverse many forms of aging."

Klatz acknowledged a feeling of disappointment that genetic engineering was required to achieve the anti-aging effect in the test animals. But, he added, "From the pure science point of view, it is impressive."

More information

Learn about lysosome function from the U.S. National Library of Medicine.

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