...and you thought overpopulation was a problem now?
Makoto Kuro-o of the University
of Texas's Southwestern Medical Center at Dallas, who led the research, said,
"This could provide a key to understanding the molecular mechanisms of aging and
opens up new areas to the potential therapy for multiple age-related diseases in
humans."
...Kuro-o
and his colleagues plan to inject the substance into normal mice to see whether
it extends their life spans and to measure the substance in humans to determine
whether levels of the protein are correlated with longevity.
It's not like I'm not
interested in this stuff - I had articles posted on the old
site...
Anyway, this
is a pretty damn big discovery! -yet even more of that change the world kind
of stuff
-Ed:
Scientists have
identified a hormone that significantly extends the life span of mice, a
discovery that could mark a crucial step toward developing drugs that boost
longevity in people.
The
hormone is the first substance identified that is produced naturally in mammals,
including humans, and can extend life span -- a long-sought goal in the intense
effort to help people live
longer.
Much more work is
needed to study the substance, and investigate whether the hormone or a similar
compound would be effective and safe in people, experts cautioned. But the
discovery opens highly promising avenues for research and provides tantalizing
new clues toward deciphering the basic biology of
aging.
"This is a
significant discovery. It's an exciting paper," said Anna McCormick of the
National Institute on Aging, which helped fund the new research, published
online yesterday by the journal Science. "It's definitely the way you would go
about designing molecules that would promote healthy aging and longevity in
people."
Makoto Kuro-o of
the University of Texas's Southwestern Medical Center at Dallas, who led the
research, said, "This could provide a key to understanding the molecular
mechanisms of aging and opens up new areas to the potential therapy for multiple
age-related diseases in
humans."
The discovery was
triggered by a study Kuro-o and his colleagues published in 1997. That study
identified a gene in mice that, when damaged, caused the animals to experience
all the hallmarks of aging in humans -- hardening of the arteries, thinning
bones, withered skin, weak lungs -- and to die prematurely. They dubbed the gene
Klotho, for the Greek goddess who spins the thread of
life.
Suspecting the gene
may play a role in regulating life span, Kuro-o and his colleagues genetically
engineered mice with overactive Klotho genes. In the latest experiments, they
found that these animals lived an average of 20 to 30 percent longer than normal
-- 2.4 to 2.6 years vs. a normal life span of about two years -- without any
signs of ill effects, according to the new
report.
"The extension of
life span is widely accepted as a reliable marker for the suppression of aging,"
Kuro-o said. "This shows the Klotho gene regulates
aging."
The researchers then
identified a small protein component, called a peptide, that the gene produces
and found it circulating in the animals' blood at double the normal
level.
After isolating and
purifying the substance and reproducing it through genetic engineering
techniques, the researchers injected the substance into normal mice. Tests on
those animals, combined with experiments involving cells in the laboratory,
indicate that the substance modulates a crucial biological pathway involved in
an array of basic metabolic functions that has become the focus of aging
research in recent
years.
"It's a pathway that
has been conserved by evolution that has been found to play a key role in
regulating life span for flies, worms, mice and probably humans," Kuro-o
said.
Studies, for example,
suggest that damping down this pathway -- known as the insulin/insulin-like
growth factor-1 signaling pathway -- may be the mechanism that extends longevity
in animals that are fed an ultra-low-calorie
diet.
The Klotho hormone
appears to have a similar effect, Kuro-o
said.
"Our work shows that
the Klotho gene is an aging-suppressor gene," he
said.
Other researchers said
the findings were remarkable because no one had previously found a naturally
occurring hormone capable of extending the life span of a
mammal.
"You have lots of
ways to shorten the life of an animal, but it's hard to get an animal to live
longer," said George M. Martin of the University of Washington, who is
scientific director of the American Federation for Aging Research. "You can kick
a radio to make it not work so well, but it's hard to make it work better. It's
quite a wonderful
discovery."
Kuro-o and his
colleagues plan to inject the substance into normal mice to see whether it
extends their life spans and to measure the substance in humans to determine
whether levels of the protein are correlated with longevity. Previous research
has shown that humans have the protein in their blood, and that people with a
certain variation of the gene are prone to age-related diseases such as heart
attacks, strokes and
osteoporosis.
Scientists
will have to determine whether the protein can be produced in sufficient
quantities to use it as a drug. It may turn out that other substances that mimic
the protein's effects would also work or be safer, Kuro-o said. "That might be
more practical," he
said.
Kuro-o and others
cautioned, however, that agents that appear effective and safe in mice often
produce complications in humans. The hormone, for example, appears to decrease
the effectiveness of insulin, which could limit its
usefulness.
"It appears to
play a role in the same pathway in people, but that doesn't necessarily mean
it's going to be as straightforward to extend life span in people as it is in
mice," said Valter Longo of the University of Southern California. "But this
adds a new component to our picture and perhaps a component that could extend
life span with few ill
effects."
Beyond the
possible clinical applications, other researchers said the finding underscores
the growing understanding of the basic biology of
aging.
"Papers like this are
filling in the pieces of the puzzle that will explain the evolutionary biology
of aging," said L. Stephen Coles of the UCLA School of Medicine.
Posted: Fri - August 26, 2005 at 01:06 AM