Aging Clinical and Experimental Research

, Volume 23, Issue 1, pp 3–10 | Cite as

Environmental and genetic factors in age-related hearing impairment

  • Roberto Bovo
  • Andrea Ciorba
  • Alessandro Martini
Review Article


Age-related hearing impairment (ARHI), or presbycusis, is a complex disease with multifactorial etiology. It is the most prevalent sensory impairment in the elderly, and may have detrimental effects on their quality of life and psychological well-being. The aim of this paper is to give an overview of the current data on ARHI, focusing mainly on environmental agents and genetic predisposition in animal models and in humans. With improvement of our understanding of ARHI, treatment other than with amplification will be hopefully possible in the long term.

Key words

Aging hearing impairment presbycusis 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Gates GA, Mills JH. Presbycusis. Lancet 2005; 366: 1111–20.PubMedCrossRefGoogle Scholar
  2. 2.
    Dalton DS, Cruickshanks KJ, Klein BE, Klein R, Wiley TL, Nondahl DM. The impact of hearing loss on quality of life in older adults. Gerontologist 2003; 43: 661–8.PubMedCrossRefGoogle Scholar
  3. 3.
    Heine C, Browning CJ. Communication and psychosocial consequences of sensory loss in older adults: overview and rehabilitation directions. Disabil Rehabil 2002; 24: 763–73.PubMedCrossRefGoogle Scholar
  4. 4.
    Van Eyken E, Van Camp G, Van Laer L. The complexity of agerelated hearing impairment: contributing environmental and genetic factors. Audiol Neurootol 2007; 12: 345–58.PubMedCrossRefGoogle Scholar
  5. 5.
    Emmerich E, Richter F, Linss V, Linss W. Frequency-specific cochlear damage in guinea pig after exposure to different types of realistic industrial noise. Hear Res 2005; 201: 90–8.PubMedCrossRefGoogle Scholar
  6. 6.
    Mulroy MJ, Henry WR, McNeil PL. Noise-induced transient microlesions in the cell membranes of auditory hair cells. Hear Res 1998; 115: 93–100.PubMedCrossRefGoogle Scholar
  7. 7.
    Boettcher FA. Susceptibility to acoustic trauma in young and aged gerbils. J Acoust Soc Am 2002; 112: 2948–55.PubMedCrossRefGoogle Scholar
  8. 8.
    International Organization of Standardization: Acoustic — Threshold of Hearing by Air Conduction as a Function of Age and Sex for Otologically Normal Persons. Geneva, International Organization of Standardization, 2000, ISO 7029.Google Scholar
  9. 9.
    Pujol R, Puel JL. Excitotoxicity, synaptic repair, and functional recovery in the mammalian cochlea: a review of recent findings. Ann NY Acad Sci 1999; 884: 249–54.PubMedCrossRefGoogle Scholar
  10. 10.
    Henderson D, Bielefeld EC, Harris KC, Hu BH. The role of oxidative stress in noise-induced hearing loss. Ear Hear 2006; 27: 1–19.PubMedCrossRefGoogle Scholar
  11. 11.
    Yamane H, Nakai Y, Takayama M et al. The emergence of free radicals after acoustic trauma and strial blood flow. Acta Otolaryngol Suppl 1995; 519: 87–92.PubMedCrossRefGoogle Scholar
  12. 12.
    Ohlemiller K, Wright JS, Dugan LL. Early elevation of cochlear reactive oxygen species following noise exposure. Audiol Neurootol 1999; 4: 229–36.PubMedCrossRefGoogle Scholar
  13. 13.
    Ohinata Y, Miller JM, Altschuler RA, Schacht J. Intense noise induces formation of vasoactive lipid peroxidation products in the cochlea. Brain Res 2000; 878: 163–73.PubMedCrossRefGoogle Scholar
  14. 14.
    Hu BH, Guo W, Wang PY, Henderson D, Jiang SC. Intense noise-induced apoptosis in hair cells of guinea pig cochleae. Acta Otolaryngol 2000; 120: 19–24.PubMedCrossRefGoogle Scholar
  15. 15.
    Lamm K, Arnold W. The effect of blood flow promoting drugs on cochlear blood flow, perilymphatic pO(2) and auditory function in the normal and noise-damaged hypoxic and ischemic guinea pig inner ear. Hear Res 2000; 141: 199–19.PubMedCrossRefGoogle Scholar
  16. 16.
    Miller JM, Brown JN, Schacht J. Iso-prostaglandin F(2alpha), a product of noise exposure, reduces inner ear blood flow. Audiol Neuro-otol 2003; 8: 207–21.CrossRefGoogle Scholar
  17. 17.
    Rybak LP, Ramkumar V. Ototoxicity. Kidney Int 2007; 72: 931–5.PubMedCrossRefGoogle Scholar
  18. 18.
    Selimoglu E. Aminoglycoside-induced ototoxicity. Curr Pharm Des 2007; 13: 119–26.PubMedCrossRefGoogle Scholar
  19. 19.
    Chen Y, Huang WG, Zha DJ et al. Aspirin attenuates gentamycin ototoxicity: from the laboratory to the clinic. Hear Res 2007; 226: 178–82.PubMedCrossRefGoogle Scholar
  20. 20.
    Forge A, Schacht J. Aminoglycoside antibiotics. Audiol Neuro-otol 2000; 5: 3–22.CrossRefGoogle Scholar
  21. 21.
    Morata TC. Chemical exposure as a risk factor for hearing loss. J Occup Environ Med 2003; 45: 676–82.PubMedCrossRefGoogle Scholar
  22. 22.
    Chang SJ, Chen CJ, Lien CH, Sung FC. Hearing loss in workers exposed to toluene and noise. Environ Health Perspect 2006; 114: 1283–6.PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    Wannamethee SG, Shaper AG. Alcohol, coronary heart disease and stroke: an examination of the J-shaped curve. Neuroepidemiology 1998; 17: 288–95.PubMedCrossRefGoogle Scholar
  24. 24.
    Popelka MM, Cruickshanks KJ, Wiley TL et al. Moderate alcohol consumption and hearing loss: a protective effect. J Am Geriatr Soc 2000; 48: 1273–8.PubMedGoogle Scholar
  25. 25.
    Fransen E, Topsakal V, Hendrickx JJ et al. Occupational noise, smoking, and a high body mass index are risk factors for age-related hearing impairment and moderate alcohol consumption is protective: a European population-based multicenter study. J Assoc Res Otolaryngol 2008; 9: 264–76.PubMedCentralPubMedCrossRefGoogle Scholar
  26. 26.
    Pratt SR, Kuller L, Talbott EO, McHugh-Pemu K, Buhari AM, Xu X. Prevalence of hearing loss in black and white elders: results of the Cardiovascular Health Study. J Speech Lang Hear Res 2009; 52: 973–89.PubMedCentralPubMedCrossRefGoogle Scholar
  27. 27.
    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; 48: 879–86.CrossRefGoogle Scholar
  28. 28.
    Danielidis V, Tsimpiris N, Balatsouras DG et al. Short-term pathophysiologic changes and histopathologic findings of the auditory pathway after closed head injury, using a rabbit model. Audiol Neuro-otol 2007; 12: 145–54.CrossRefGoogle Scholar
  29. 29.
    Iwai H, Lee S, Inaba M et al. Prevention of accelerated presbycusis by bone marrow transplantation in senescence-accelerated mice. Bone Marrow Transplant 2001; 28: 323–8.PubMedCrossRefGoogle Scholar
  30. 30.
    Iwai H, Lee S, Inaba M et al. Correlation between accelerated presbycusis and decreased immune functions. Exp Gerontol 2003; 38: 319–25.PubMedCrossRefGoogle Scholar
  31. 31.
    Kurien M, Thomas K, Bhanu TS. Hearing threshold in patients with diabetes mellitus. J Laryngol Otol 1989; 103: 164–8.PubMedCrossRefGoogle Scholar
  32. 32.
    Kakarlapudi V, Sawyer R, Staecker H. The effect of diabetes on sensorineural hearing loss. Otol Neurotol 2003; 24: 382–6.PubMedCrossRefGoogle Scholar
  33. 33.
    Frisina ST, Mapes F, Kim S, Frisina DR, Frisina RD. Characterization of hearing loss in aged type II diabetics. Hear Res 2006; 211: 103–13.PubMedCentralPubMedCrossRefGoogle Scholar
  34. 34.
    Fukushima H, Cureoglu S, Schachern PA, Paparella MM, Harada T, Oktay MF. Effects of type 2 diabetes mellitus on cochlear structure in humans. Arch Otolaryngol Head Neck Surg 2006; 132: 934–8.PubMedCrossRefGoogle Scholar
  35. 35.
    Janssen GM, Maassen JA, van Den Ouweland JM. The diabetes- associated 3243 mutation in the mitochondrial tRNA(Leu(UUR)) gene causes severe mitochondrial dysfunction without a strong decrease in protein synthesis rate. J Biol Chem 1999; 274: 29744–8.PubMedCrossRefGoogle Scholar
  36. 36.
    Nomiya R, Nomiya S, Kariya S et al. Generalized arteriosclerosis and changes of the cochlea in young adults. Otol Neurotol 2008; 29: 1193–7.PubMedCrossRefGoogle Scholar
  37. 37.
    Paparella MM, Hanson DG, Rao KN, Ulvestad R. Genetic sensorineural deafness in adults. Ann Otol Rhinol Laryngol 1975; 84: 459–72.PubMedGoogle Scholar
  38. 38.
    Schuknecht HF. Techniques for study of cochlear function and pathology in experimental animals: development of the anatomical frequency scale of the cat. Arch Otolaryngol 1953; 58: 377–97.CrossRefGoogle Scholar
  39. 39.
    Schuknecht HF, Gacek MR. Cochlear pathology in presbycusis. Ann Otol Rhinol Laryngol 1993; 102: 1–16.PubMedGoogle Scholar
  40. 40.
    Ohlemiller KK.Age-related hearing loss: the status of Schuknecht’s typology. Curr Opin Otolaryngol Head Neck Surg 2004; 12: 439–43.PubMedCrossRefGoogle Scholar
  41. 41.
    Jennings CR, Jones NS. Presbyacusis. J Laryngol Otol 2001; 115: 171–8.PubMedGoogle Scholar
  42. 42.
    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: 1–12.PubMedCrossRefGoogle Scholar
  43. 43.
    Nelson EG, Hinojosa R. Presbycusis: A human temporal bone study of individuals with flat audiometric patterns of hearing loss using a new method to quantify stria vascularis volume. Laryngoscope 2003; 113: 1672–86.PubMedCrossRefGoogle Scholar
  44. 44.
    Karlsson KK, Harris JR, Svartengren M. Description and primary results from an audiometric study of male twins. Ear Hear 1997; 18: 114–20.PubMedCrossRefGoogle Scholar
  45. 45.
    Gates GA, Couropmitree NN, Myers RH. Genetic associations in age-related hearing thresholds. Arch Otolaryngol Head Neck Surg 1999; 125: 654–9.PubMedCrossRefGoogle Scholar
  46. 46.
    Christensen K, Frederiksen H, Hoffman HJ. Genetic and environmental influences on self-reported reduced hearing in the old and oldest old. J Am Geriatr Soc 2001; 49: 1512–7.PubMedCrossRefGoogle Scholar
  47. 47.
    Johnson KR, Erway LC, Cook SA, Willott JF, Zheng QY. A major gene affecting age-related hearing loss in C57BL/6J mice. Hear Res 1997; 114: 83–92.PubMedCrossRefGoogle Scholar
  48. 48.
    Johnson KR, Zheng QY. Ahl2, a second locus affecting age-related hearing loss in mice. Genomics 2002; 80: 461–4.PubMedCentralPubMedCrossRefGoogle Scholar
  49. 49.
    Nemoto M, Morita Y, Mishima Y et al. Ahl3, a third locus on mouse chromosome 17 affecting age-related hearing loss. Biochem Biophys Res Commun 2004; 324: 1283–8.PubMedCrossRefGoogle Scholar
  50. 50.
    Zheng QY, Ding D, Yu H, Salvi RJ, Johnson KR. A locus on distal chromosome 10 (ahl4) affecting age-related hearing loss in A/J mice. Neurobiol Aging 2009; 30: 1693–705.PubMedCentralPubMedCrossRefGoogle Scholar
  51. 51.
    Noben-Trauth K, Zheng QY, Johnson KR, Nishina PM. mdfw: a deafness susceptibility locus that interacts with deaf waddler (dfw). Genomics 1997; 44: 266–72.PubMedCrossRefGoogle Scholar
  52. 52.
    Di Palma F, Holme RH, Bryda EC et al. Mutations in Cdh23, encoding a new type of cadherin, cause stereocilia disorganization in waltzer, the mouse model for Usher syndrome type 1D. Nat Genet 2001; 27: 103–7.PubMedCrossRefGoogle Scholar
  53. 53.
    Johnson KR, Erway LC, Cook SA, Willott JF, Zheng QY. A major gene affecting age-related hearing loss in C57BL/6J mice. Hear Res 1997; 114: 83–92.PubMedCrossRefGoogle Scholar
  54. 54.
    Noben-Trauth K, Zheng QY, Johnson KR. Association of cadherin 23 with polygenic inheritance and genetic modification of sensorineural hearing loss. Nat Genet 2003; 35: 21–3.PubMedCentralPubMedCrossRefGoogle Scholar
  55. 55.
    Pickles JO, Brix J, Comis SD et al. The organization of tip links and stereocilia on hair cells of bird and lizard basilar papillae. Hear Res 1989; 41: 31–42.PubMedCrossRefGoogle Scholar
  56. 56.
    Davis RR, Kozel P, Erway LC. Genetic influences in individual susceptibility to noise: a review. Noise Health 2003; 5: 19–28.PubMedGoogle Scholar
  57. 57.
    Fridberger A, Flock A, Ulfendahl M, Flock B. Acoustic overstimulation increases outer hair cell Ca2+ concentrations and causes dynamic contractions of the hearing organ. Proc Natl Acad Sci USA 1998; 95: 7127–32.PubMedCrossRefGoogle Scholar
  58. 58.
    Kozel PJ, Friedman RA, Erway LC et al. Balance and hearing deficits in mice with a null mutation in the gene encoding plasma membrane Ca2+-ATPase isoform 2. J Biol Chem 1998; 273: 18693–6.PubMedCrossRefGoogle Scholar
  59. 59.
    Street VA, McKee-Johnson JW, Fonseca RC, Tempel BL, Noben-Trauth K. Mutations in a plasma membrane Ca2+- ATPase gene cause deafness in deafwaddler mice. Nat Genet 1998; 19: 390–4.PubMedCrossRefGoogle Scholar
  60. 60.
    DeStefano AL, Gates GA, Heard-Costa N, Myers RH, Baldwin CT. Genome-wide linkage analysis to presbycusis in the Framingham Heart Study. Arch Otolaryngol Head Neck Surg 2003; 129: 285–9.PubMedCrossRefGoogle Scholar
  61. 61.
    Garringer HJ, Pankratz ND, Nichols WC, Reed T. Hearing impairment susceptibility in elderly men and the DFNA18 locus. Arch Otolaryngol Head Neck Surg 2006; 132: 506–10.PubMedCrossRefGoogle Scholar
  62. 62.
    Van Eyken E, Van Laer L, Fransen E et al. KCNQ4: a gene for age-related hearing impairment? Hum Mutat 2006; 27: 1007–16.PubMedCrossRefGoogle Scholar
  63. 63.
    Kubisch C, Schroeder BC, Friedrich T et al. KCNQ4, a novel potassium channel expressed in sensory outer hair cells, is mutated in dominant deafness. Cell 1999; 96: 437–46.PubMedCrossRefGoogle Scholar
  64. 64.
    Takumi Y, Matsubara A, Tsuchida S, Ottersen OP, Shinkawa H, Usami S. Various glutathione S-transferase isoforms in the rat cochlea. Neuroreport 2001; 12: 1513–6.PubMedCrossRefGoogle Scholar
  65. 65.
    Lautermann J, Crann SA, McLaren J, Schacht J. Glutathione-dependent antioxidant systems in the mammalian inner ear: effects of aging, ototoxic drugs and noise. Hear Res 1997; 114: 75–82.PubMedCrossRefGoogle Scholar
  66. 66.
    Sha SH, Taylor R, Forge A, Schacht J. Differential vulnerability of basal and apical hair cells is based on intrinsic susceptibility to free radicals. Hear Res 2001; 155: 1–8.PubMedCrossRefGoogle Scholar
  67. 67.
    Unal M, Tamer L, Doĝruer ZN, Yildirim H, Vayisoĝlu Y, Camdeviren H. N-acetyltransferase 2 gene polymorphism and presbycusis. Laryngoscope 2005; 115: 2238–41.PubMedCrossRefGoogle Scholar
  68. 68.
    Van Eyken E, Van Camp G, Fransen E et al. The N-acetyltransferase 2 polymorphism NAT2_6A is a causative factor for age related hearing impairment. J Med Genet 2007; 44: 570–8.PubMedCrossRefGoogle Scholar
  69. 69.
    O’Grady G, Boyles AL, Speer M, DeRuyter F, Strittmatter W, Worley G. Apolipoprotein E alleles and sensorineural hearing loss. Int J Audiol 2007; 46: 183–6.PubMedCrossRefGoogle Scholar
  70. 70.
    Wallace DC. Mitochondrial DNA in aging and disease. Sci Am 1997; 277: 40–7.PubMedCrossRefGoogle Scholar
  71. 71.
    Fischel-Ghodsian N, Bykhovskaya Y, Taylor K et al. Temporal bone analysis of patients with presbycusis reveals high frequency of mitochondrial mutations. Hear Res 1997; 110: 147–54.PubMedCrossRefGoogle Scholar
  72. 72.
    Bai U, Seidman MD, Hinojosa R, Quirk WS. Mitochondrial DNA deletions associated with aging and possibly presbycusis: a human archival temporal bone study. Am J Otol 1997; 18: 449–53.PubMedGoogle Scholar
  73. 73.
    Markaryan A, Nelson EG, Hinojosa R. Quantification of the mitochondrial DNA common deletion in presbycusis. Laryngoscope 2009; 119: 1184–9.PubMedCrossRefGoogle Scholar
  74. 74.
    Seidman MD, Bai U, Khan MJ et al. Association of mitochondrial DNA deletions and cochlear pathology: a molecular biologic tool. Laryngoscope 1996; 106: 777–83.PubMedCrossRefGoogle Scholar
  75. 75.
    Markaryan A, Nelson EG, Hinojosa R. Major arc mitochondrial DNA deletions in cytochrome c oxidase deficient human cochlear spiral ganglion cells. Acta Otolaryngol 2010; 130: 780–7.PubMedCrossRefGoogle Scholar
  76. 76.
    Ohlemiller KK, Rice ME, Lett JM, Gagnon PM. Absence of strial melanin coincides with age-associated marginal cell loss and endocochlear potential decline. Hear Res 2009; 249: 1–14.PubMedCrossRefGoogle Scholar
  77. 77.
    Bärrenas M. Pigmentation and noise-induced hearing loss: is the relationship between pigmentation and noise-induced hearing loss due to an ototoxic pheolamin interaction or to otoprotective eumelan effects. In Prasher D, Luxon L, Eds. Advances in Noise Research. Biological effect of noise. London: Whurr Ed, 1998: 59–70.Google Scholar
  78. 78.
    Voisey J, van Daal A. Agouti: from mouse to man, from skin to fat. Pigment Cell Res 2002; 15: 10–8.PubMedCrossRefGoogle Scholar
  79. 79.
    Friedman RA, Van Laer L, Huentelman MJ et al. GRM7 variants confer susceptibility to age-related hearing impairment. Hum Mol Genet 2009; 18: 785–96.PubMedCrossRefGoogle Scholar
  80. 80.
    Van Laer L, Van Eyken E, Fransen E et al. The grainyhead like 2 gene (GRHL2), alias TFCP2L3, is associated with age-related hearing impairment. Hum Mol Genet 2008; 17: 159–69.PubMedCrossRefGoogle Scholar
  81. 81.
    Peters LM, Anderson DW, Griffith AJ et al. Mutation of a transcription factor, TFCP2L3, causes progressive autosomal dominant hearing loss, DFNA28. Hum Mol Genet 2002; 11: 2877–85.PubMedCrossRefGoogle Scholar
  82. 82.
    Kujawa SG, Liberman MC. Acceleration of age-related hearing loss by early noise exposure: evidence of a misspent youth. J Neurosci 2006; 26: 2115–23.PubMedCentralPubMedCrossRefGoogle Scholar
  83. 83.
    Folmer RL, Griest SE, Martin WH. Hearing conservation education programs for children: a review. School Health 2002; 72: 51–7.CrossRefGoogle Scholar
  84. 84.
    Li H, Liu H, Heller S. Pluripotent stem cells from the adult mouse inner ear. Nat Med 2003; 9: 1293–9.PubMedCrossRefGoogle Scholar
  85. 85.
    Bielefeld EC, Tanaka C, Chen GD, Henderson D. Age-related hearing loss: Is it a preventable condition? Hear Res 2010; 264: 98–107PubMedCentralPubMedCrossRefGoogle Scholar
  86. 86.
    Revoltella RP, Papini S, Rosellini A. Cochlear repair by transplantation of human cord blood CD133+ cells to nod-scid mice made deaf with kanamycin and noise. Cell Transplant 2008; 17: 665–78.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Internal Publishing Switzerland 2011

Authors and Affiliations

  • Roberto Bovo
    • 1
  • Andrea Ciorba
    • 1
  • Alessandro Martini
    • 1
  1. 1.Department of AudiologyUniversity of FerraraFerraraItaly

Personalised recommendations