Escaped Proteins Add to Age-Related Hearing Loss for
Senior Citizens
UF researchers find protein that is central to
oxidative damage to cells and leads to age-related hearing loss
Nov. 10, 2009 - Age-related hearing loss is the
most common sensory disorder among the elderly. More than 40 percent of
U.S. senior citizens (older than 65) suffer from age-related hearing
loss, according to data from the National Health Survey. It is estimated
this will affect more than 28 million by 2030. But scientists are still
trying to figure out what cellular processes govern or contribute to the
loss.
Now a University of Florida team and researchers
from University of Wisconsin and three other institutions have
identified a protein that is central to processes that cause oxidative
damage to cells and lead to age-related hearing loss.
The findings help point the way toward a new target
for antioxidant therapies and will be published online this week in the
Proceedings of the National Academy of Sciences.
One theory of aging holds that free radicals damage
components of mitochondria, the energy center of cells. Such damage
accumulates over time, leading to a destabilization of the mitochondria,
which leads to release of certain proteins.
"Within the mitochondria these proteins cause life,
but when they're out they're deadly," professor Christiaan Leeuwenburgh,
Ph.D., chief of the biology of aging division at UF's College of
Medicine and a member of the Institute on Aging.
The cell death triggered by the escaped proteins
lead to physical effects we associate with aging, such as hearing loss.
"Because of the high prevalence of this disorder,
AHL is a major social and health problem," said Shinichi Someya, first
author of the paper and a postdoctoral fellow in the group of Tomas
Prolla of University of Wisconsin.
Age-related hearing loss involves the death of
certain sensory hair, nerve and membrane cells in the inner ear. Since
the hair and nerve cells do not regenerate in humans, their death leads
to permanent hearing loss.
One protein called Bak is known to play a role in
the weakening of the mitochondrial membrane. The more of the protein
present, the leakier the mitochondrial membrane becomes, allowing
harmful proteins to travel out into the rest of the cell.
Bak is typically induced by oxidative stress and
its levels increase as people age. The researchers wanted to see whether
its absence would prevent the age-related hearing loss that is
associated with the death of certain sensory hair, nerve and membrane
cells in the inner ear.
Hearing tests showed that Bak-deficient middle-aged
mice were found to have hearing levels comparable to that of young mice.
In addition, fewer of the critical hearing cells died, compared with
so-called wild type mice that did not have the protein deficiency.
To examine how resistant the inner ear cells of the
Bak-deficient mice were, the researchers exposed cells to a chemical
that causes oxidative stress. Such stress generally induces Bak
expression in inner ear cells.
There was only minor loss of cochlear cells at all
doses of the stressor chemical, in contrast with the level observed in
wild-type animals. The researchers concluded that Bak promotes cochlear
cell death in response to oxidative stress.
"This paper clearly shows us that oxidative stress
causes hearing loss," said Jinze Xu, a postdoctoral fellow in
Leeuwenburgh's group, and second author of the paper.
So if oxidative stress triggers damage and death of
hearing-related cells, enhancing the antioxidant defenses of the
mitochondria should reduce such damage.
The researchers found that both in animals that had
excess amounts of an enzyme that scavenges reactive oxygen species, as
well as in those who were fed certain antioxidants orally, onset of
age-related hearing loss was delayed.
"It looks like a viable biological target that may
be applicable to drug use," Leeuwenburgh said. "The issue is always
timing — when to start antioxidant interventions at what combination and
what dose."
Caloric restriction, another way to reduce
oxidative damage, has previously been shown to extend life and prevent
age-related hearing loss in the type of mice used in the study. With the
new findings, the investigators propose that one of the ways that
restriction of calories acts is by reducing the level of cell death that
is induced by the protein Bak.
"This extends research into life extension by
caloric restriction into a whole new area that hasn't been looked at
before," said Huber Warner, Ph.D., associate dean for research a
University of Minnesota College of Biological Sciences and former
director of the biology of aging program at the National Institute on
Aging, who was not involved in the study.
"The work shows that rather than caloric
restriction just having an overall effect on metabolism of nutrients,
bak modulation can have segmental effects on particular physical systems
that have age-related problems in humans."
Keep up with the latest news for senior citizens, baby
boomers
Nov. 10, 2009 - Age-related hearing loss is the
most common sensory disorder among the elderly. More than 40 percent of
U.S. senior citizens (older than 65) suffer from age-related hearing
loss, according to data from the National Health Survey. It is estimated
this will affect more than 28 million by 2030. But scientists are still
trying to figure out what cellular processes govern or contribute to the
loss.