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In scientific first, Einstein researchers correct decline in organ function associated with old age
Date:8/10/2008

rveillance system, in particular, becomes less efficient as cells become older, resulting in a buildup of undigested proteins within the cells. She also detected the primary cause for this age-related decline: a fall-off in the number of lysosomal receptors capable of binding chaperones and their damaged proteins. Could replenishing lost receptors in older animals maintain the efficiency of this protein-removal system throughout an animal's lifespan and, perhaps, maintain the function of the animal's cells and organs as well?

To find out, Dr. Cuervo created a transgenic mouse model equipped with an extra gene one 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 and at a time of her choosing, merely by changing the animals' diet.

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 in their normal counterparts of the same age and, in fact, just as efficiently as in normal six-month old mice.

Does maintaining efficient protein clearance in liver cells of an older animal translate into better functioning for the liver as a whole? Since a key function of the liver is metabolizing chemicals, Dr. Cuervo answered this question by injecting a muscle relaxant into very old transgenic mice and very old normal mice. The very old transgenic mice metabolized the muscle relaxant much more quickly than very old normal mice and at a rate comparable to young normal mice.

"Our study showed that functions can be maintained in older animals so long as damaged prote
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Contact: Karen Gardner
kgardner@aecom.yu.edu
718-430-3101
Albert Einstein College of Medicine
Source:Eurekalert

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