Aging Process Halted in Mouse Liver

Aug. 11, 2008 -- Scientists have stopped the aging 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 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, said Cuervo.

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

Specialized 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 metabolize 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.