[tt] [Fwd: [GRG] Researchers uncover details about how dietary restriction slows down aging]

[Brian Atkins]

-------- Original Message --------
Subject: [GRG] Researchers uncover details about how dietary restriction	slows 
down aging
Date: Fri, 18 Apr 2008 10:24:20 -0400
From: Derya Unutmaz MD <derya at mac.com>
Reply-To: Gerontology Research Group <grg at lists.ucla.edu>
To: Gerontology Research Group <grg at lists.ucla.edu>
References: <20080417181147.DLIH7569.mta10.adelphia.net at StephenColes-PC.grg.org>

This is an interesting and significant study of interest:

University of Washington scientists have uncovered details about the
mechanisms through which dietary restriction slows the aging process.
Working in yeast cells, the researchers have linked ribosomes, the
protein-making factories in living cells, and Gcn4, a specialized
protein that aids in the expression of genetic information, to the
pathways related to dietary response and aging. The study, which was
led by UW faculty members Brian Kennedy and Matt Kaeberlein, appears
in the April 18 issue of the journal Cell.

Previous research has shown that the lifespan-extending properties of
dietary restriction are mediated in part by reduced signaling through
TOR, an enzyme involved in many vital operations in a cell. When an
organism has less TOR signaling in response to dietary restriction,
one side effect is that the organism also decreases the rate at which
it makes new proteins, a process called translation.

In this project, the UW researchers studied many different strains of
yeast cells that had lower protein production. They found that
mutations to the ribosome, the cell's protein factory, sometimes led
to increased life span. Ribosomes are made up of two parts -- the
large and small subunits -- and the researchers tried to isolate the
life-span-related mutation to one of those parts.

“What we noticed right away was that the long-lived strains always had
mutations in the large ribosomal subunit and never in the small
subunit,” said the study's lead author, Kristan Steffen, a graduate
student in the UW Department of Biochemistry.

The researchers also tested a drug called diazaborine, which
specifically interferes with synthesis of the ribosomes' large
subunits, but not small subunits, and found that treating cells with
the drug made them live about 50 percent longer than untreated cells.
Using a series of genetic tests, the scientists then showed that
depletion of the ribosomes' large subunits was likely to be increasing
life span by a mechanism related to dietary restriction -- the TOR
signaling pathway.

“We knew that dietary restriction decreased TOR signaling, and that
decreased TOR signaling reduced translation or protein production, but
this was the first direct evidence that all three were acting in the
same genetic pathway,” said Kennedy, an associate professor of
biochemistry.

"The big question then became what’s happening in these translation-
deficient cells to slow aging," added Kaeberlein, an assistant
professor of pathology. "That’s when Vivian MacKay, a co-author on the
study, had the idea to look at Gcn4."

Gcn4 is a specialized protein called a transcription factor, which
helps transfer genetic information during cell growth. The protein is
activated when a cell is starving for amino acids. What made Gcn4
interesting to the UW team was its unique mode of regulation.

"When ribosomes aren’t working at 100 percent capacity, most proteins
are made less efficiently, but Gcn4 is different," explained Dr.
MacKay, a research professor of biochemistry. "Sometimes, you actually
get more Gcn4 produced even when everything else is going down. That's
precisely what we found in the longer-lived yeast strains with
mutations in the large subunit of the ribosome."

To make the link between Gcn4 and longevity, the scientists then asked
whether preventing the increase of Gcn4 would block life span
extension. In every case, cells lacking Gcn4 did not respond as
strongly as Gcn4-positive cells.

"The increased production of Gcn4 in long-lived yeast strains,
combined with the requirement of Gcn4 for full life-span extension,
makes a compelling case for Gcn4 as an important downstream factor in
this longevity pathway," Kaeberlein said.

Although scientists don’t yet know whether Gcn4 plays a similar role
in organisms other than yeast, Kennedy points out that worms, flies,
mice and humans all have Gcn4-like proteins that appear to be
regulated in a similar way.

"The role of TOR and translation in aging is known to be conserved
across many different species, so it’s plausible that this function of
Gcn4 is conserved as well," Kennedy said. Future research will be
aimed at testing this hypothesis.

"Clearly TOR signaling is one component, and perhaps the major
component, of the beneficial health effects associated with dietary
restriction," said Kaeberlein. "The difficulty with TOR as a
therapeutic target, however, is the potential for negative side
effects. As we learn more of the mechanistic details behind how TOR
regulates aging, we will hopefully be able to identify even better
targets for treating age-associated diseases in people."




-- 
Brian Atkins
Singularity Institute for Artificial Intelligence
http://www.singinst.org/
-------------- next part --------------
An embedded and charset-unspecified text was scrubbed...
Name: file:///C:/DOCUME~1/BRIAN/LOCALS~1/TEMP/nsmail-1.txt
Url: http://postbiota.org/pipermail/tt/attachments/20080418/16290a10/attachment.txt