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Posted On: July 22, 2008

By the time we reach age 60, 30 percent of us will have some degree of age-related hearing loss, and by age 80, this percentage increases to 50 percent.

Age-related hearing loss, called presbycusis, is the gradual and progressive loss of hearing that begins for many in midlife and continues to increase throughout the aging process. It affects men more than women and represents a complex interplay of genetic susceptibility and environmental insults.

Hearing loss is the most common sensory deficit among older adults, and its effects can be socially and psychologically devastating, leading to loneliness, isolation, anxiety and depression. Fortunately, hearing aids and assistive listening devices can help those who are willing to give them a try; however, denial, fear of change, embarrassment, and stigmatization often stand in the way of a successful amplification outcome. 

Presbycusis was first described more than 100 years ago, and Schuknecht provided a useful guideline for researchers over 40 years ago with his delineation of four types of presbycusis, including sensory, neural, strial, and cochlear conductive, and admixtures of the four.¹ Rather than remaining a permanent and unalterable condition as first thought, presbycusis is currently viewed as a disorder that is potentially both preventable and medically treatable.    

Knowledge of the correlates of presbycusis, both environmental and genetic, is necessary to successful management. The environmental factors possibly related to presbycusis have been extensively studied over the years and range from excessive noise to ototoxic drugs, chemical exposure, diseases, tobacco, alcohol, head injury, bone mineral density, immune system deficiency, diet, hormones, and socioeconomic status.² In contrast, little is known about the specific genes involved in presbycusis, especially in humans.    

Genes are the basic units of heredity, with the 20,000 or so in the human genome strung along 23 pairs of chromosomes contained within each of the estimated 100 trillion cells that make up each individual human being. When the four chemical bases of genes, designated ACGT, are mixed up or deleted in the 3-billion-letter alphabet of life, the resultant genetic mutations lead to heritable diseases or syndromes. Hundreds of genes are involved in hereditary hearing loss, leading to syndromes such as Waardenberg, Usher and Pendred.     

More than 4,500 genes participate in the development and maintenance of the human inner ear, making it the most genetically complex organ in the human body.³ The process of discovering genes involved in presbycusis, a long and involved scientific endeavor, gains even more relevance with the findings of a 2007 Brandeis University study of fraternal male twin pairs, ranging in age from 52 to 60 years, as part of the Vietnam Era Twin Study of Aging (VETSA).⁴ About two-thirds of the hearing loss in the individual subjects' better ears could be accounted for by genetic factors. In the subjects' poorer ears, about one-half of the hearing loss was due to genes, the study concluded.

The research suggests middle-aged and older people with a genetic vulnerability to hearing loss should be particularly careful about environmental risk factors such as harmful noises and medications whose side effects could be detrimental to hearing. 

As early as 2003, researchers from Michigan State University reported a set of gene mutations causing progressive hearing loss.⁵ The gene involved, DFNA 20 on chromosome 17, is known to play an essential role in the structure of the cochlea. "Until now, no mutations had been discovered in this gene, so this finding is expected to provide new insights that will help researchers understand more about the biology of progressive loss," says Rachel Fisher, PhD, one of the project leaders. "One possibility is that the mutations interfere with processes that allow ears to repair damage done by noise or aging."

Again in 2003, researchers at the Boston University School of Public Health identified six chromosomal regions on four chromosomes that showed evidence of linkage to age-associated hearing impairment in humans.⁶ Some of the regions overlapped with genes already known to cause congenital deafness. In another more recent linkage study conducted in 2006, Indiana University School of Medicine researchers implicated a seventh region on chromosome 3, overlapping the DFNA18 locus.⁷ The DFNA18 gene has been reported to cause a form of progressive hereditary hearing loss. The results suggest that "this region may contain an important locus for hearing loss in the general population," says Terry Reed, professor of medical and molecular genetics at IU.

In 2006, Belgian researchers identified KCNQ4 on chromosome 1 as a candidate susceptibility gene for age-related hearing impairment,⁸ and researchers at the University of Virginia (UVA) Health System reported in 2007 of a technique for transferring a correct form of the KCNQ4 gene into human hair cells harvested from the inner ears of patients with hearing loss.⁹ "This is a critically important step forward," says Jeffrey Hold, associate professor of neuroscience and otolaryngology at UVA. "We hope this breakthrough will propel the field of hearing and deafness research toward our collective goal of curing genetic and acquired deafness."

Another promising line of research is the impairment of cochlear function through mitochondrial DNA deletions. Mitochondrial DNA, a collection of 38 genes, supplies energy to organs such as the cochlea. In a study of donated temporal bones with verified presbycusis, Chinese researchers found a deletion called mtDNA4977 in half the ears, causing a potential reduction in oxygen supply to the cochlea and associated neural structures.¹⁰ Such genetic deletions often result from the release of cell-damaging free oxygen radicals as part of the aging process, and antioxidant compounds presently in development for treating noise-induced hearing loss may also help prevent hearing damage due to growing older.

A few other genes such as NAT2 and DFNA24 are presently implicated in human presbycusis, and many more are undoubtably waiting to be discovered.  

The study of genetic factors in presbycusis took another step forward with the 2006 announcement that researchers at the Translational Genomics Research Institute (TGen), the House Ear Institute (HEI) and other organizations have initiated a study to identify genes and genetics interactions involved in age-related hearing loss.¹¹ "This project will put age-related hearing loss at the forefront of genetic research," according to Guy Van Camp of the University of Antwerp.

References

1.  Schuknecht, H. (l964). Further observations on the pathology of presbycusis. Archives of Otolaryngology, 80: 369-82.

2.  Van Eyken, E, Van Camp, G, Van Laer, L. (2007). The complexity of age-related hearing impairment: contributing environmental and genetic factors. Audiology & Neurotology, 12(6): 345-58. Epub 2007 July 27.

3.  Pobojewski, S. (2006). What did you say? Medicine at Michigan. Accessed online at www.medicineatmichigan.org/magazine/2006/spring/hearing/default.asp.

4.  Brandeis University (2007, November 16). Genes influence age-related hearing loss. ScienceDaily. Accessed online at www.sciencedaily.com/releases/2007/11/071114183244.htm.

5.  Michigan State University (2003, October 30). Team discovers gene mutations that cause hearing loss. ScienceDaily. Accessed online at www.sciencedaily.com/releases/2003/10/031030064544.htm.

6.  DeStefano, Al, Gates, GA, Heard-Costa, N, et al. (2003). Genomewide linkage analysis to presbycusis in the Framingham Heart Study. Archives of Otolaryngology-Head & Neck Surgery, 129(3): 285-9.

7.  Indiana University (2006, May 17). Researchers closer to finding a genetic cause of hearing loss in aging. ScienceDaily. Accessed online at www.sciencedaily.com/releases/2006/05/060517082542.htm

8.  Van Eyken, E, Van Laer, L, Fransen, E, et al. (2006). KCNQ4: a gene for age-related hearing impairment? Human Mutation, 27(10): 1007-16.

9. University of Virginia Health System (2007, June 14). Genes in human inner ear cells restored. ScienceDaily. Accessed online at www.sciencedaily.com/releases/2007/06/070614082041.htm

10.  Dai, P, Yang, W, Jiang, S, et al. (2004). Correlation of cochlear blood supply with mitochondrial DNA common deletion in presbyacusis. Acta Otolaryngologica, 124(2): 130-6.

11.  New study aims to uncover genetic factors for hearing loss. (2006). House Ear Institute. Accessed online at www.hei.org/news/releases/060829gen.htm.

Jess Dancer is professor emeritus of audiology at the University of Arkansas at Little Rock. Contact him at jedancer@ualr.edu.