Researchers created a mouse model with boosted levels of a receptor that is integral to getting rid of damaged protein, according to a paper in Nature Medicine.

Scientists at the Albert Einstein College of Medicine of Yeshiva University report that they were able to prevent age-related decline in the liver of mice. They showed that the livers of older animals functioned as well as they did when the animals were much younger.

With age, the process of finding, digesting, and recycling damaged proteins become less efficient. About 30% of damaged cellular proteins are handled by a surveillance system that uses molecules known as chaperones to seek out damaged proteins. After finding such a protein, the chaperone attaches to one of the cell’s lysosome membrane-bound sacs through a receptor molecule where it gets digested.

Ana Maria Cuervo, associate professor in the departments of developmental and  molecular biology, medicine and anatomy and structural biology at Einstein, and leader of the current study, had already discovered that the chaperone surveillance system becomes less efficient primarily due to a fall-off in the number of lysosomal receptors capable of binding chaperones and their damaged proteins.

To further investigate this, Dr. Cuervo created a transgenic mouse model with an extra gene that codes for the receptor that normally declines in number with increasing age. Another genetic manipulation allowed Dr. Cuervo to turn on this extra gene only in the liver.

To keep the level of the receptor constant throughout life, Dr. Cuervo waited until mice were six months old (the age that the chaperone system’s efficiency begins to decline) before turning on the added receptor gene. When the mice were examined at 22 to 26 months of age (equivalent to approximately 80 years old in humans), the liver cells of transgenic mice digested and recycled protein far more efficiently than their normal counterparts of the same age. In fact, just as efficiently as in normal six-month old mice.

“Our study showed that functions can be maintained in older animals so long as damaged proteins continue to be efficiently removed, strongly supporting the idea that protein buildup in cells plays an important role in aging itself,” says Dr. Cuervo. “Even more important, these results show that it’s possible to correct this protein logjam that occurs in our cells as we get older.”

Dr. Cuervo next plans to study animal models of Alzheimer’s, Parkinson’s, and other neurodegenerative brain diseases to see whether maintaining efficient protein clearance in the brain might help in treating them. Dr. Cuervo will also investigate whether maintaining efficient protein clearance in all the body’s tissues will influence longevity and prevent the functional losses associated with growing old.

The results are published in the advanced online edition of Nature Medicine.

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