'Escaped' Proteins Add To Hearing Loss in Elderly

November 2009

Editor: Here's a report on research into age-related hearing loss from the folks at the University of Florida.

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Gainesville, Fla - A University of Florida team, researchers from the 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, according to a statement issued by the University of Florida Health Science Center

The findings help point the way toward a new target for antioxidant therapies and will soon be published online 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, PhD, chief of the biology of aging division at UF's College of Medicine and a member of the Institute on Aging, said in the statement.

The cell death triggered by the escaped proteins lead to physical effects we associate with aging, such as hearing loss.

More than 40% of people in the United States older than 65 suffer from age-related hearing loss, according to data from the National Health Survey. It is estimated that the condition will affect more than 28 million Americans by 2030.

"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 statement says. 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.