[tt] [Fwd: [GRG] Researchers correct decline in organ function associated with old age]

[Brian Atkins]

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Subject: [GRG] Researchers correct decline in organ function associated with	old age
Date: Sun, 10 Aug 2008 14:14:36 -0700
From: Brian Chiko <brian at juvensa.com>
Reply-To: Gerontology Research Group <grg at lists.ucla.edu>
To: 'Gerontology Research Group' <grg at lists.ucla.edu>
References: 
<20080809000611.BTHQ13299.cdptpa-omta04.mail.rr.com at StephenColes-PC.grg.org>

  Albert Einstein <http://www.aecom.yu.edu>  College of Medicine

In scientific first, Einstein researchers correct decline in organ function
associated with old age

(BRONX, NY) - As people age, their cells become less efficient at getting
rid of damaged protein - resulting in a buildup of toxic material that is
especially pronounced in Alzheimer's, Parkinson's disease, and other
neurodegenerative disorders.

Now, for the first time, scientists at the Albert Einstein College of
Medicine of Yeshiva University have prevented this age-related decline in an
entire organ - the liver - and shown that, as a result, the livers of older
animals functioned as well as they did when the animals were much younger.
Published in the online edition of Nature Medicine, these findings suggest
that therapies for boosting protein clearance might help stave off some of
the declines in function that accompany old age. The study's senior author
was Dr. Ana Maria Cuervo, associate professor in the departments of
developmental & molecular biology, medicine and anatomy & structural biology
at Einstein.

The cells of all organisms have several surveillance systems designed to
find, digest and recycle damaged proteins. Many studies have documented that
these processes become less efficient with age, allowing protein to
gradually accumulate inside cells. But aging researchers continue debating
whether this protein buildup actually contributes to the functional losses
of aging or instead is merely associated with those losses. The Einstein
study was aimed at resolving the controversy.

One of these surveillance systems - responsible for handling 30 percent or
more of damaged cellular protein - uses molecules known as chaperones to
seek out damaged proteins. After finding such a protein, the chaperone
ferries it towards one of the cell's many lysosomes - membrane-bound sacs
filled with enzymes. When the chaperone and its cargo "dock" on a receptor
molecule on the lysosome's surface, the damaged protein is drawn into the
lysosome and rapidly digested by its enzymes.

In previous work, Dr. Cuervo found that the chaperone surveillance 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 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, thereby perhaps helping us to enjoy healthier lives well into old
age."

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. "Most people
with these conditions are born with a mutation that gives rise to defective
proteins, but they don't experience symptoms until later in life," says Dr.
Cuervo. "We think that's because their protein-clearance systems can handle
abnormal proteins when the person is younger but get overwhelmed as their
efficiency falls with age. By preventing this decline in protein clearance,
we may be able to keep these people free of symptoms for a longer time."

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. "There's reason to hope that
drugs exerting a similar effect throughout the body may help us enjoy
healthier lives well into old age," says Dr. Cuervo. Meanwhile, she notes,
evidence is mounting that two dietary interventions -low-fat and
calorie-restricted diets - help cells to maintain efficient protein
clearance.

###

Cong Zhang, a graduate student working in Dr. Cuervo's laboratory, was the
lead author of the Nature Medicine study. The research was supported by
grants from the National Institute on Aging, an Ellison Medical Foundation
Award and a Glenn Foundation Award.





-- 
Brian Atkins
Singularity Institute for Artificial Intelligence
http://www.singinst.org/
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