Age-related hearing loss may be lessened or prevented in the future by regulating an enzyme that neutralizes free-oxygen radicals, destructive molecules that can destroy sensory hair cells of the inner ear, suggests preliminary research conducted at UB.

Using mice lacking one or both components of the genes responsible for production of the antioxidant enzyme superoxide dismutase, or SOD, the UB researchers showed that age-related hearing loss was greater and progressed faster in mice deficient in the enzyme than in mice with a normal genetic makeup and SOD production that served as a control group.

"Before this present study, we thought that hearing loss was a normal process of aging," said Richard Salvi, co-director of the Center for Hearing and Deafness and leader of the research group.

"Then we found people with no loss, and we figured it was related to a low-noise environment. Now we believe that at least some age-related hearing loss is due to a genetic deficiency in antioxidant enzymes, such as SOD. If we are able to regulate the enzyme and modulate the number of free radicals present, there is hope for a therapy for age-related hearing loss."

The researchers used mice in which one or both components of the gene responsible for production of SOD had been eliminated, along with mice with a normal amount of SOD.

In one study, the researchers measured auditory sensory-cell loss in mice that were young (2 months), middle-aged (7 months) and aged (17 months). None were subjected to any interventions, such as noise exposure, that could cause cell damage, yet researchers found dramatic differences among the groups.

"The control-group mice had some sensory-cell loss just from being old, but far less than the mice lacking SOD," said Robert Burkhard, a principal researcher on the study. "This suggests that SOD may play a role in cell loss, a condition that leads to hearing loss. People who have deficiencies in SOD or other antioxidant enzymes may be at greater risk for losing their hearing."

In a companion study, researchers led by Sandra McFadden measured actual hearing loss, as well as sensory-cell loss, in mice that were 13 months old, an age roughly equivalent to 50-60 human years. As in the previous study, none of the mice had been exposed to interventions that could affect hearing.

Mice lacking one component of the SOD gene had greater hearing loss than the control-group mice, particularly at the higher frequencies, results showed. The mice lacking both genes were very likely to be deaf at 13 months.

"We know that the free radicals produced throughout the body as by-products of normal cell metabolism can cause extensive damage to living tissues, including the sensory hair cells in the inner ear, if they are not neutralized by antioxidant enzymes," McFadden said. "We think that SOD deficiencies may increase cochlear vulnerability to environmental insults, such as noise or drugs, as well as to injury from normal free-radical activity during aging.

"An increase in antioxidant enzymes that neutralize free radicals, such as SOD, may protect the cochlea from these insults and prevent or lessen hearing loss."

For more information on the two studies, see http://www.buffalo.edu/news/Latest/DeafMiceSalvi.html

McFadden is the author of another study presented at the meeting, that showed that the brain center responsible for hearing retains the ability to reorganize itself and respond normally during periods of reduced activity resulting from damage to the auditory nerve endings in the inner ear.

The researchers in this study also found that the damaged nerve endings that transmit impulses from hair cells to the brain can recover from injury, but at a significantly slower rate than the brain. These findings have important implications for restoring lost hearing in humans.

"It is not news that the brain can reorganize itself after damage to the peripheral sensory organ," said McFadden. "What is new here," she said, "is our finding that the brain can reorganize itself again after the peripheral sensory organ recovers from damage and sensory input is restored. This may be important with regard to restoring hearing in humans, through the use of hearing aids or cochlear implants, for example, because it demonstrates that the brain remains plastic after a period of sensory deprivation."

The finding of central-auditory-system plasticity also may explain why many hearing-aid users go through an adjustment period before they perceive an improvement, McFadden said.

Researchers induced reversible damage to the auditory-nerve endings in the cochlea, the primary sensory organ of the inner ear, in eight chinchillas, and monitored auditory-signal transmission between the damaged nerve and the location in the brain that receives its signals.

Measurements of activity at the brain site and at the auditory-nerve fibers were taken at days 1, 5, 10 and 30 following the induced injury.

"Remarkably, we found that the brain recovers sooner than the ear itself," McFadden said. "Specifically, responses recorded from the inferior colliculus recovered to normal in five days, long before the responses recorded from the auditory nerve, which took up to 30 days.

"These results tell us that auditory-nerve fibers carrying impulses from the ear to the brain can regrow, which is essential to the recovery of hearing, and that the central auditory system in the brain reorganizes itself to maintain its function while the nerve fibers are damaged. It then reorganizes itself again as nerve function is restored."

For more information on the study, see http://www.buffalo.edu/news/Latest/McFaddenHearing.html