Researchers Report 10-Fold Life Extension In Complex
Animal
By News Account (as reported on ScientificBlogging.com)
posted: February 2008
Researchers at the University of Arkansas
for Medical Sciences (UAMS) have reported a 10-fold life extension
in the complex animal C. elegans, tiny worms that live in
the soil.
Reported in the February 2008 issue of
the journal Aging Cell, the discovery was made by a team of
researchers headed by Robert Shmookler Reis, professor in
the UAMS Departments of Geriatrics, Biochemistry/Molecular
Biology and Pharmacology/Toxicology and research scientist
at the Central Arkansas Veterans Healthcare System.
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C. elegans are barely visible to the eye
but are helping scientists unravel the causes of aging and
understand what determines life span, Reis said. During the
past 15 years, more than 80 mutations have been found that
extend life in C. elegans, including components of a worm
signaling pathway (a set of genes that responds to signals
from the environment or within the worm) that is equally related
to insulin signaling and insulin-like growth factor (IGF-1)
signaling in mammals.
Insulin alerts cells that there are nutrients
in the blood ready to be used, whereas IGF-1 stimulates growth.
Interfering with insulin signaling results in insulin resistance,
a condition that can develop into diabetes. Interfering with
IGF-1 signaling produces effects in mammals more akin to those
seen in long-lived worms. Mice mildly deficient in IGF-1 receptor
are long-lived and appear healthy, Reis said, adding that
the longest-lived humans tend to have diminished IGF-1 signaling
as well.
“These observations hint that processes
discovered in the worm also are relevant to aging in humans,”
Reis said, “but we shouldn’t expect exact parallels.”
Reis’ team discovered that a mutant
in the insulin/ IGF-1 pathway of C. elegans slows development
but ultimately produces adults he described as “super
survivors,” able to resist levels of toxic chemicals
that would kill an ordinary worm. Although the adult lifespan
of C. elegans is normally only two to three weeks, half of
the mutant worms were still alive after six months, with some
surviving to nine months.
“We knew we had found something
amazing,” said Srinivas Ayyadevara, Ph.D., research
assistant professor in the UAMS Donald W. Reynolds Institute
on Aging. “These worms continue to look and act like
normal worms of one-tenth their age.”
Reis cautioned that the discovery does
not mean that an 800-year human life span is just around the
corner. “Worms have a short lifespan to begin with,
so it seems to be relatively easy to prod them to live longer.
Other mutations, which extend the life of C. elegans up to
2.5-fold, give a much smaller benefit in mice,” he said.
“The important thing is that we
now have a pretty good idea of what we should try in order
to increase mouse lifespan by 50 to 100 percent. We are on
a path now that might lead to similar gains from a single
genetic change or drug given to mice, and eventually to a
treatment that could benefit humans.”
To view the article, visit http://www.uams.edu/update/news/aging_cell.pdf.
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