• E-mail
• Print
• Comment
• Font Size
• Digg
• del.icio.us
• Discuss article

Molecular and Neural Perspectives on Age-Related Hearing Loss

Posted on: Tuesday, 27 July 2004, 06:00 CDT

Age-related hearing loss or presbycusis is the number one communication problem-and one of the top three chronic medical conditions-of our older population. This condition can be particularly problematic in work and interpersonal situations.

Gradual loss in communication abilities often leads to miscommunications and social/familial isolation. It is now recognized that age-related hearing loss results from changes in the inner ear, as well as in parts of the brain used for hearing. Cochlear dysfunctions responsible for progressive sensorineural hearing loss generally begin with loss of outer hair cells, degeneration of spiral ganglion cells (auditory nerve fibers of the 8th cranial nerve), and, as studied by Richard Schmiedt's group at the Medical University of South Carolina, disruptions in potassium metabolism in the stria vascularis that produces endolymph. These cochlear conditions lead to elevated thresholds in tones and speech, and contribute to problems in suprathreshold complex sound processing.

The main complaint of older listeners is trouble perceiving speech and music in background noise. They can hear speech, but cannot readily understand it. This is due to the cochlear problems referred to above. In addition, it can result from deficits in portions of the brain used for hearing-the central auditory system.

The brain processing abnormalities that occur with age have been discovered by us and several other auditory neuroscience groups, and include: loss of inhibitory neurotransmitters with age (GABA, glycine) as discovered by Donald Caspary's team at Southern Illinois University; changes in neural wiring pathways in the brainstem delineated by James Willott at Northern Illinois University and by our team in Rochester; alterations in optimal levels of neural calcium regulators as studied by Martha Zettel and William O'Neill of our Rochester group; declines in single-neuron processing of temporal and spatial sound features and cues (gaps, amplitude modulation) as shown by Joseph Walton at the University of Rochester Medical School; and alterations in neural potassium channels with age as demonstrated by James Ison and Paul Alien of our Rochester team.

Our recent molecular investigations using gene arrays and mouse animal models are pointing the way to further understanding of the molecular genetic bases of presbycusis. Over 100 genes that can cause early profound deafness have been identified thus far. Surprisingly, no genes that are causative for presbycusis have yet been identified in humans. We are engaged in mouse gene-array studies to identify possible candidate genes for presbycusis in concert with molecular genetics studies in human subjects in our laboratories headed by Robert Frisina, Sr., Dina Newman, Chin-To Fong, Gary Skuse and Susan Frisina, RN.

In experiments involving mice of different ages, we have found that genes related to the immune system, to glucose metabolism, to key protein structure, to inner ear growth factors and to cochlear neurotransmitters, significantly alter their expression with age and result in age-related peripheral sensorineural hearing losses that are similar to presbycusis in humans. We pursued this in collaboration with Andrei Yakovlev, Xiaoxia Zhu, Mary D'Souza, and Martha Erhardt. To investigate these gene expression changes in older men and women, we are using animal model gene-array studies as guides of what to look for.

Our coordinated energies are focused on three major areas related to the neural and molecular bases of presbycusis: improved audiological differential diagnosis pertaining to function and site of lesion; pharmacological and technological interventions; and molecular therapies. We routinely take into account other age- related medical conditions such as Type II diabetes, hypothyroidism, cardiovascular conditions, and hormone-replacement therapies. We have found that some of these co-morbidities can exacerbate or accelerate different aspects of the peripheral and/or central characteristics of presbycusis. We will continue working toward chemical (medication, diet) and molecular (surgical, genetic) strategies aimed at preventing, slowing, and curing age-related sensory problems as typified by presbycusis.

The main complaint of older listeners is trouble perceiving speech and music in background noise. Theg can hear speech, but cannot readilg understand it

Robert D. Frisina is professor of otolaryngology, neurobiology & anatomy, and biomedical engineering, and is associate chair of otolaryngology in the medical school of the University of Rochester. he also holds joint appointments at the National Technical Institute for the Deaf and biological sciences department at the Rochester Institute of Technology. Contact him at rdf@q.ent.rochester.edu.

Copyright American Speech-Language-Hearing Association Jul 20, 2004

More News in this Category