Clinical and Health Affairs
Age-Related Hearing Loss
By Tina Huang, M.D.
Abstract
Age-related hearing loss or presbycusis is hearing loss that progressively worsens with age. With the expected increase in the number of elderly in the United States, the problem is anticipated to be increasingly common, and the impact widely felt in coming years. This article discusses the causes and mechanisms of this type of hearing loss and current research that may lead to new treatments.
By 2050, more than 86 million adults in the United States (20.7% of the population) will be age 65 and older.1 Compare that with the fact that in 2000, 35 million individuals in this country were in that age range. One of the health concerns affecting this growing segment of the population will likely be hearing loss. Although prevalence estimates vary, hearing loss is common among older adults. One study has estimated the prevalence of hearing loss among people 75 years and older at 40%.2 Another epidemiologic study reported the prevalence of hearing loss in people older than 50 years as being almost 50% and in those older than 80 as being 90%.3
Hearing loss that is gradual and progressive and that accompanies age is known as age-related hearing loss (ARHL) or presbycusis. It is characterized by decreased hearing sensitivity, decreased ability to understand speech in a noisy environment, slowed central processing of acoustic stimuli, and impaired ability to detect the location of a sound. It is typically described as a downward sloping high-frequency loss, meaning that hearing is better in the low and middle frequencies than in the high frequencies, but it may be associated with various types of auditory system dysfunction that progress with age such as a progressive flat hearing loss. Additionally, a decline in speech understanding often accompanies the loss in hearing thresholds.
Although age-related hearing loss is not life-threatening, it affects quality of life and can have a negative effect on a person’s health. It diminishes an individual’s ability to communicate effectively, jeopardizes one’s autonomy, presents a safety concern, and has been correlated with an increased incidence of clinical depression and social isolation.4 For those reasons, research on hearing and hearing loss is ongoing and important.
The Mechanisms of Hearing and Hearing Loss
In order to begin to understand some of the possible mechanisms involved in the development of age-related hearing loss, a brief review of the anatomy of the auditory system may be helpful.
Sound waves travel through the air and enter the external auditory canal. They make contact with the tympanic membrane, which begins to vibrate. The vibrations are then amplified through the ossicles of the middle ear to the cochlea. The vibrations create a wave within the fluid in the cochlea. The mechanical energy of the wave is then transmitted to the hair cells, which turn the mechanical energy into electrical impulses that then travel through the cochlear nerve to the brain.
The peripheral auditory system consists of the external auditory canal, components of the middle ear, and the cochlea. The cochlea houses the organ of Corti, which contains 2 types of neurosensory cells, the inner and outer hair cells. There are 3 rows of outer hair cells and a single row of inner hair cells. The outer hair cells have been shown to be more susceptible to many types of damage including aging, but the inner hair cells appear to be relatively resistant. The hair cells are organized tonotopically along the cochlea, with the basal turn of the cochlea corresponding to high-frequency hearing, the middle turn corresponding to mid-frequency hearing, and the apical turn corresponding to low-frequency hearing.
The lateral wall of the cochlea contains 2 structures that are critical for maintaining the ionic balance: the spiral ligament and the stria vascularis. These structures contain active ion channels that control sodium and potassium levels within the cochlear fluid, thereby maintaining the electrical potential needed for hair cell function within the cochlea. The stria vascularis is extremely well-vascularized and metabolically very active. The spiral ganglion holds the neuronal cell bodies, which connect the hair cells to the cochlear nerve.
The central auditory pathway is involved in complex processing of sound into recognizable language and music. It begins at the cochlear nerve and moves through the cochlear nuclei, into the superior olivary complex, to the inferior colliculus, and through the medial geniculate body before finally ending in the auditory cortex.
Three major components of the cochlea have been associated with different types of ARHL. A down-sloping high-frequency hearing loss may be associated with a sensory hearing loss that is the result of outer hair cell dysfunction (Figure 1). A flat, progressive hearing loss may be associated with a metabolic hearing loss caused by lateral wall dysfunction, particularly that of the stria vascularis (Figure 2). Neural hearing loss, which is thought to affect speech understanding, may be associated with dysfunction in the spiral ganglion. Of course, a person may exhibit elements of several types of hearing loss.
Several histologic studies support loss of outer hair cells as well as loss of lateral wall components in ARHL. Studies of human temporal bone from patients with ARHL have shown a loss of capillaries within the spiral ligament and diminished flow even in capillaries that appear normal.5,6 Changes in blood viscosity, red blood cell structure, blood flow velocity, and capillary permeability have also been found in ARHL. Animal studies have shown outer hair cell loss, particularly in the basal turn of the cochlea, and atrophy of the lateral wall associated with ARHL.7 Degeneration of the stria vascularis, including derangement of the strial microvasculature, and loss of sodium/potassium channels causes a loss of cochlear electrical potential, which results in hearing loss similar to that found in the aged.7 Such changes also have been found in human temporal bones.8 A recent study has shown primarily outer hair cell loss with more variable inner hair cell loss and even fewer specimens with stria vascularis loss.9 The study also found spiral ganglion cell loss in all specimens. The degree of loss in cochlear cells was associated with increasing hearing loss.
Functional studies also confirm a cochlear lesion in ARHL. Comparison of the function of outer hair cells with that of spiral ganglion cells has shown that it is the outer hair cells that are responsible for hearing decline. Additionally, otoacoustic emissions, sound generated by the outer hair cells, have been shown to decrease with age, likely signifying outer hair cell damage.
The role of degeneration of the central auditory pathway in ARHL is controversial. Several studies analyzing causes for diminished speech understanding and discrimination showed that worsening speech understanding was likely the result of damage to the peripheral auditory system.6 Additionally, not all histologic studies have shown a correlation between the degree of central degeneration and the degree of hearing loss. On the other hand, loss of function of the cochlear nerve has been shown in aged animals with reduced synchronous neural activity.7 This asynchrony may contribute to the decline in temporal resolution in ARHL. Other animal studies have shown decreased function in the cochlear nucleus.10 Although there clearly is central auditory pathway dysfunction in the elderly, its role in hearing loss has yet to be clearly defined.7,11 In fact, evidence tends to point toward peripheral dysfunction leading to central dysfunction.10
Searching for Causes
Since it may have a variety of causes, research is being done on possible genetic causes of ARHL as well as on molecular causes. Understanding of the role of genetics in ARHL has moved forward with the development of several mouse models. The C57 strain develops significant hearing loss early in life and has been found to have a mutation in the Ahl gene, which codes for cadherin 23, a calcium-binding transmembrane protein that is found primarily in hair cell stereocilia.8,11 Other strains have been developed that also carry Ahl. A familial study has revealed a defective gene, POU 4F3, that may be responsible for ARHL.6 The Framingham cohort study has also shown a familial predilection towards ARHL.6
The Ahl gene also interacts with mitochondrial DNA (mtDNA).8 The role of mitochondria in ARHL has become a promising field of study. MtDNA are more susceptible to mutations than nuclear DNA because of their close proximity to free radicals and reactive oxygen species created by mitochondria during the process of oxidative phosphorylation. MtDNA also lack many of the repair mechanisms found in nuclear DNA.6 The frequency of a common deletion in human mtDNA has been found to increase with age, and a common deletion in rat mtDNA was associated with increased hearing loss.6,11 Additionally, as many as 67% of patients with mtDNA disorders also manifest hearing loss.12 Seidman restricted the calorie intake of a group of rats and treated another with several antioxidants. The calorie-restricted rats were found to have the least amount of ARHL, the fewest mtDNA mutations, and the least amount of outer hair cell loss.12,13 Those given antioxidants also showed better results when compared with controls. A transgenic mouse lacking a mtDNA repair gene was noted to have premature aging and a decreased life span.14 The mice were also noted to have an accelerated ARHL, increased loss of basal turn outer hair cells, and increased loss of basal turn spiral ganglion cells. Multiple researchers have tried to find an association between ARHL and other age-related disorders. Cardiovascular disease, blood hyperviscosity, atherosclerosis and hypercholesterolemia, calcium imbalance, and hyperlipidemia have all been studied for a possible connection with ARHL.6 However, no clear association has been found.
Age-related changes in the cochlea are proposed to be a function of both genetics and environmental stresses (primarily noise exposure), which lead to alterations in electrolyte homeostasis and cellular metabolism.15 Changes have been shown to occur in the neurons, hair cells (sensory cells), and supporting cells of the cochlea. Noise exposure by itself can cause hair cell damage, leading to hearing loss. The hearing loss caused by noise exposure can mimic ARHL, and ARHL on top of hearing loss caused by noise exposure certainly will be greater.
Conclusion
Studies to prevent or ameliorate hearing loss are happening around the world. At the University of Minnesota, researchers are testing a combination of orally administered antioxidants in C57 mice in an attempt to reduce the degree of ARHL. Their ultimate goal is to create an antioxidant supplement for human use. Preliminary studies using stem cells to ameliorate the degree of ARHL have also been done. Stem cells derived from adult bone marrow, once localized to the cochlea, will be stimulated with local growth factors in order to encourage differentiation into either hair cells or lateral wall cells. The stem cells being used are derived from adult bone-marrow cells.
Because ARHL is such a large public health problem, and will become even more pervasive as the population ages, research in this field is vital. It is likely that multiple factors contribute to the hearing loss associated with aging, and research being done in other fields on aging may also shed light on the mechanisms of ARHL. The goal of researchers is to minimize age-
related hearing loss. It may be impossible to completely prevent any degree of hearing loss. But because hearing aids are the only option for hearing rehabilitation at this time, any improvement in hearing would improve a person’s quality of life. MM
Tina Huang is an assistant professor in the department of otolaryngology at the University of Minnesota.
References
1. U.S. Census. Table 2a. Projected population of the United States, by age and sex: 2000 to 2050. Available at: http://www.census.gov/ipc/www/usinterimproj/natprojtab02a.pdf. Accessed August 25, 2007.
2. Seidman MD, Kahn MJ, Bai U, Shirwany N, Quirk WS. Biologic activity of mitochondrial metabolites on aging and age-related hearing loss. Am. J Otol. 2000;21(2):161-7.
3. Cruickshanks KJ, Wiley TL, Tweed TS, et al. Prevalence of hearing loss in older adults in Beaver Dam, Wisconsin. The Epidemiology of Hearing Loss Study. Am J Epidemiol. 1998;148(9):879-86.
4. Cacciatore F, Napoli C, Abete P, Marciano E, Triassi M, Rengo F. Quality of life determinants and hearing function in an elderly population: Osservatorio Geriatrico Compano study group. Gerontol. 1999;45(6):323-8.
5. Seidman MD, Quirk WS, Shirwany NA. Mechanisms of alterations in the microcirculation of the cochlea. Ann NY Acad Sci. 1999;884:226-32.
6. Jennings CR, Jones NS. Presbyacusis. J Laryngol Otol. 2001;115(3):171-8.
7. Gates GA, Mills JH. Presbycusis. Lancet. 2005;366(9491):1111-20.
8. Gratton MA, Vazquez AE. Age-related hearing loss: current research. Curr Opin Otolaryngol Head Neck Surg. 2003;11(5):367-71.
9. Nelson EG, Hinojosa R. Presbycusis: a human temporal bone study of individuals with downward sloping audiometric patterns of hearing loss and review of the literature. Laryngoscope. 2006;116(S112):1-12.
10. Frisina RD, Walton JP. Age-related structural and functional changes in the cochlear nucleus. Hear Res. 2006;Jun-Jul:216-23.
11. Ohlemiller KK. Age-related hearing loss: the status of Schuknecht’s typology. Curr Opin Otolaryngol Head Neck Surg. 2004;12(5):439-43.
12. Seidman MD. Effects of dietary restriction and antioxidants on presbycusis. Laryngoscope. 2000;110(5 Pt 1):727-38.
13. Seidman MD, Ahmad N, Joshi D, Seidman J, Thawani S, Quirk WS. Age-related hearing loss and its association with reactive oxygen species and mitochondrial DNA damage. Acta Otolaryngol. 2004;May(552):16-24.
14. Yamasoba T, Someya S, Yamada C, Weindruch R, Prolla TA, Tanokura M. Role of mitochondrial dysfunction and mitochondrial DNA mutations in age-related hearing loss. Hear Res. 2007;226(1-2):185-93.
15. Petropoulou C, Chondrogiani N, Simoes D, et al. Aging and longevity. A paradigm of complementation between homeostatic mechanisms of genetic control. Ann. NY Acad. Sci. 2000;908:133-42.