X-Message-Number: 18141
From: "trippgary" <>
Subject: Aging switch discovered
Date: Wed, 12 Dec 2001 01:02:29 -0500

Two University of Colorado at Boulder researchers working with GenoPlex Inc.
in Denver have identified a biological switch that controls lifespan in tiny
worms, a finding that could have applications for mammals, including people.
The switch, known as DAF-16, is a protein that can either lengthen or
shorten the lifespan in the eyelash-sized roundworm, C. elegans, said
CU-Boulder psychology Professor Thomas Johnson. Johnson, who is a fellow in
the university's Institute for Behavioral Genetics, or IBG, said DAF-16 is a
critical part of a complex signaling pathway that involves insulin and
glucose.

IBG Research Associate and principal author Samuel Henderson and Johnson are
publishing a paper Dec. 11 on the topic in the prestigious journal Current
Biology. Henderson and Johnson both are associated with GenoPlex.

The key to DAF-16 is whether it penetrates the nucleus of cells, said
Henderson. "When it does penetrate the nucleus, it appears to turn on a
switch to lengthen roundworm lives."

The switch, which is controlled by food availability, temperature and
stress, likely has a homologue, or similar protein, in mammals, including
humans, said Johnson. Insulin released with glucose in humans goes up and
stores more fat when they consume sugar, inhibiting DAF-16 to enter the
nucleus of the cells. It is likely that the same process occurs in other
animals, he said.

Henderson has identified a molecule that embodies a trade off, said Johnson.
"If DAF-16 is 'on,' it triggers less reproduction, more efficient cell
repair and longer lives. On the other hand, if DAF-16 is 'off,' the result
is more reproduction, worse cell repair and a shortened lifespan," he said.

Johnson authored a milestone paper in 1990 in Science magazine showing that
mutating a single gene in roundworms could double their lifespan -- the
first researcher discovered the lifespan of an animal could be increased by
genetic mutation. Since then, researchers around the world have been
tinkering with proteins and genes of C. elegans in attempts to understand
how lifespan can be increased.

The increased longevity, said Johnson, is due to the ability of C. elegans
to resist environmental 'insults.' The mutated C. roundworm species from
Johnson's early work have been linked to oxygen metabolism. Just as metal
rusts when it is exposed to certain oxygen compounds, so do living cells, he
said.

"The longer lived species of C. elegans have a higher resistance to free
radicals and environmental stress," said Johnson.

When DAF-16 is located in the cytoplasm of cells outside of the nucleus, it
is in the "off" mode, said Henderson. It is only when the cell is seeking
more food that DAF-16 enters the cell nucleus, triggering a cascade of
biochemical events that lead to a longer lifespan.

There is a good possibility scientists could develop a pharmaceutical
intervention that would trigger translocation of DAF-16 into the cell
nucleus of a variety of animals, including humans, said Henderson. This
would cause organisms to lower their reproduction level and fight off the
negative impacts of free radicals.

University Of Colorado Researchers Identify Switch That Controls Aging In
Worms

Two University of Colorado at Boulder researchers working with GenoPlex Inc.
in Denver have identified a biological switch that controls lifespan in tiny
worms, a finding that could have applications for mammals, including people.
The switch, known as DAF-16, is a protein that can either lengthen or
shorten the lifespan in the eyelash-sized roundworm, C. elegans, said
CU-Boulder psychology Professor Thomas Johnson. Johnson, who is a fellow in
the university's Institute for Behavioral Genetics, or IBG, said DAF-16 is a
critical part of a complex signaling pathway that involves insulin and
glucose.

IBG Research Associate and principal author Samuel Henderson and Johnson are
publishing a paper Dec. 11 on the topic in the prestigious journal Current
Biology. Henderson and Johnson both are associated with GenoPlex.

The key to DAF-16 is whether it penetrates the nucleus of cells, said
Henderson. "When it does penetrate the nucleus, it appears to turn on a
switch to lengthen roundworm lives."

The switch, which is controlled by food availability, temperature and
stress, likely has a homologue, or similar protein, in mammals, including
humans, said Johnson. Insulin released with glucose in humans goes up and
stores more fat when they consume sugar, inhibiting DAF-16 to enter the
nucleus of the cells. It is likely that the same process occurs in other
animals, he said.

Henderson has identified a molecule that embodies a trade off, said Johnson.
"If DAF-16 is 'on,' it triggers less reproduction, more efficient cell
repair and longer lives. On the other hand, if DAF-16 is 'off,' the result
is more reproduction, worse cell repair and a shortened lifespan," he said.

Johnson authored a milestone paper in 1990 in Science magazine showing that
mutating a single gene in roundworms could double their lifespan -- the
first researcher discovered the lifespan of an animal could be increased by
genetic mutation. Since then, researchers around the world have been
tinkering with proteins and genes of C. elegans in attempts to understand
how lifespan can be increased.

The increased longevity, said Johnson, is due to the ability of C. elegans
to resist environmental 'insults.' The mutated C. roundworm species from
Johnson's early work have been linked to oxygen metabolism. Just as metal
rusts when it is exposed to certain oxygen compounds, so do living cells, he
said.

"The longer lived species of C. elegans have a higher resistance to free
radicals and environmental stress," said Johnson.

When DAF-16 is located in the cytoplasm of cells outside of the nucleus, it
is in the "off" mode, said Henderson. It is only when the cell is seeking
more food that DAF-16 enters the cell nucleus, triggering a cascade of
biochemical events that lead to a longer lifespan.

There is a good possibility scientists could develop a pharmaceutical
intervention that would trigger translocation of DAF-16 into the cell
nucleus of a variety of animals, including humans, said Henderson. This
would cause organisms to lower their reproduction level and fight off the
negative impacts of free radicals.

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