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Age-Related Hearing Loss: Mitochondrial Biochemical Pathways and Molecular Targets

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Free Radicals in ENT Pathology

Abstract

Aging is characterized by a general decline in physiological function that leads to organism dysfunction, and eventually to death (Proc Natl Acad Sci USA 91(23):10771-10778, 1994). Hearing loss is a common feature of aging and is the third most prevalent chronic health condition in older adults in the United States (Vital Health Stat 10(194):1-89, 1997). Age-related hearing loss (AHL) is a multifactorial sensory disorder caused by aging, heredity and environmental factors such as exposure to noise or ototoxic chemicals/drugs (Hear Res 303:30-38, 2013, 2005; J Pathol 211(2):188–197, 2007). How do these risk factors lead to the pathogenesis of AHL at the molecular level? There is a growing body of evidence suggesting that mitochondrial dysfunction plays a central role in the development of age-related disorders, including AHL (Cell 120(4):483–495, 2005; Annu Rev Genet 39:359–407, 2005; Clin Genet 71:379–391, 2007; Science 309:481–484, 2005; Mech Ageing Dev 131(7-8):480–486, 2010; Proc Natl Acad Sci USA 91(23):10771-10778, 1994; Science 308:1909–1911, 2005). In support of this theory, hearing loss is commonly one of the symptoms of human mitochondrial disorders (Clin Genet 71:379–391, 2007). Yet, specific biochemical pathways of mitochondrial dysfunction in AHL remain poorly characterized. This chapter summarizes what has been learned about the mitochondrial biochemical pathways which are potential targets of AHL, and examines the link between aging, mitochondrial dysfunction, and hearing loss in rodents and humans. We also discuss calorie restriction as a potential intervention to prevent AHL by increasing oxidative stress resistance or enhancing mitochondrial function.

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References

  • Aon MA, Stanley BA, Sivakumaran V, Kembro JM, O’Rourke B, Paolocci N, Cortassa S (2012) Glutathione/thioredoxin systems modulate mitochondrial H2O2 emission: an experimental-computational study. J Gen Physiol 139(6):479–491

    Google Scholar 

  • Balaban RS, Nemoto S, Finkel T (2005) Mitochondria, oxidants, and aging. Cell 120(4):483–495

    Article  CAS  PubMed  Google Scholar 

  • Banaclocha MM (2001) Therapeutic potential of N-acetylcysteine in age-related mitochondrial neurodegenerative diseases. Med Hypotheses 56:472–477

    Article  CAS  PubMed  Google Scholar 

  • Bared A, Ouyang X, Angeli S, Du LL, Hoang K, Yan D, Liu XZ (2010) Antioxidant enzymes, presbycusis, and ethnic variability. Otolaryngol Head Neck Surg 143(2):263–268

    Article  PubMed Central  PubMed  Google Scholar 

  • Boyd-Kimball D, Sultana R, Abdul HM, Butterfield DA (2005) Gamma-glutamylcysteine ethyl ester-induced up-regulation of glutathione protects neurons against Abeta-mediated oxidative stress and neurotoxicity: implications for Alzheimer’s disease. J Neurosci Res 79(5):700–706

    Article  CAS  PubMed  Google Scholar 

  • Chinnery PF, Elliott C, Green GR, Rees A, Coulthard A, Turnbull DM, Griffiths TD (2000) The spectrum of hearing loss due to mitochondrial DNA defects. Brain 123(Pt 1):82–92

    Article  PubMed  Google Scholar 

  • Collins JG (1997) Prevalence of selected chronic conditions: United States, 1990-1992. Vital Health Stat 10(194):1–89

    Google Scholar 

  • Evans P, Halliwell B (1999) Free radicals and hearing. Cause, consequence, and criteria. Ann N Y Acad Sci 884:19–40

    Google Scholar 

  • Finkel T, Holbrook NJ (2000) Oxidants, oxidative stress and the biology of ageing. Nature 408(6809):239–247

    Article  CAS  PubMed  Google Scholar 

  • Fischel-Ghodsian N (2003) Mitochondrial deafness. Ear Hear 24:303–313

    Article  PubMed  Google Scholar 

  • Fontana L, Partridge L, Longo VD (2010) Extending healthy life span-from yeast to humans. Science 328(5976):321–326

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Gurney ME, Pu H, Chiu AY, Dal Canto MC, Polchow CY, Alexander DD, Caliendo J, Hentati A, Kwon YW, Deng HX et al (1994) Motor neuron degeneration in mice that express a human Cu, Zn superoxide dismutase mutation. Science 264(5166):1772–1775

    Article  CAS  PubMed  Google Scholar 

  • Haass C, Selkoe DJ (2007) Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer’s amyloid beta-peptide. Nat Rev Mol Cell Biol 8(2):101–112

    Article  CAS  PubMed  Google Scholar 

  • Halliwell B, Gutteridge J (2007) Free radicals in biology and medicine. Oxford University Press, Oxford

    Google Scholar 

  • Haramizu S, Nagasawa A, Ota N, Hase T, Tokimitsu I, Murase T (2009) Different contribution of muscle and liver lipid metabolism to endurance capacity and obesity susceptibility of mice. J Appl Physiol 106:871–879

    Article  CAS  PubMed  Google Scholar 

  • Harman D (1956) Aging: a theory based on free radical and radiation chemistry. J Gerontol 11(3):298–300

    Article  CAS  PubMed  Google Scholar 

  • Jacono AA, Hu B, Kopke RD, Henderson D, Van De Water TR, Steinman HM (1998) Changes in cochlear antioxidant enzyme activity after sound conditioning and noise exposure in the chinchilla. Hear Res 117(1–2):31–38

    Article  CAS  PubMed  Google Scholar 

  • Jiang H, Talaska AE, Schacht J, Sha SH (2007) Oxidative imbalance in the aging inner ear. Neurobiol Aging 28(10):1605–1612

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Johnson KR, Gagnon LH, Longo-Guess C, Kane KL (2012) Association of a citrate synthase missense mutation with age-related hearing loss in A/J mice. Neurobiol Aging 33(8):1720–1729

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kitahara T, Li HS, Balaban CD (2004) Localization of the mitochondrial uncoupling protein family in the rat inner ear. Hear Res 196(1–2):39–48

    Article  CAS  PubMed  Google Scholar 

  • Kłapcińska B, Derejczyk J, Wieczorowska-Tobis K et al (2000) Antioxidant defense in centenarians (a preliminary study). Acta Biochim Pol 47(2):281–292

    PubMed  Google Scholar 

  • Kokotas H, Petersen MB, Willems PJ (2007) Mitochondrial deafness. Clin Genet 71:379–391

    Article  CAS  PubMed  Google Scholar 

  • Konings A, Van Laer L, Pawelczyk M, Carlsson PI, Bondeson ML, Rajkowska E, Dudarewicz A, Vandevelde A, Fransen E, Huyghe J, Borg E, Sliwinska-Kowalska M, Van Camp G (2007) Association between variations in CAT and noise-induced hearing loss in two independent noise-exposed populations. Hum Mol Genet 16(15):1872–1883

    Article  CAS  PubMed  Google Scholar 

  • Kujoth GC, Hiona A, Pugh TD, Someya S, Panzer K, Wohlgemuth SE, Hofer T, Seo AY, Sullivan R, Jobling WA et al (2005) Mitochondrial DNA mutations, oxidative stress, and apoptosis in mammalian aging. Science 309:481–484

    Article  CAS  PubMed  Google Scholar 

  • Kujoth GC, Bradshaw PC, Haroon S, Prolla TA (2007) The role of mitochondrial DNA mutations in mammalian aging. PLoS Genet 3:e24

    Article  PubMed Central  PubMed  Google Scholar 

  • Lightfoot JT, Turner MJ, Debate KA, Kleeberger SR (2001) Interstrain variation in murine aerobic capacity. Med Sci Sports Exerc 33:2053–2057

    Article  CAS  PubMed  Google Scholar 

  • Lindsten T, Ross AJ, King A, Zong WX, Rathmell JC, Shiels HA, Ulrich E, Waymire KG, Mahar P, Frauwirth K et al (2000) The combined functions of proapoptotic Bcl-2 family members bak and bax are essential for normal development of multiple tissues. Mol Cell 6:1389–1399

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Liu XZ, Yan D (2007) Ageing and hearing loss. J Pathol 211(2):188–197

    Article  CAS  PubMed  Google Scholar 

  • Liu YM, Li XD, Guo X, Liu B, Lin AH, Rao SQ (2010) Association between polymorphisms in SOD1 and noise-induced hearing loss in Chinese workers. Acta Otolaryngol 130(4):477–486

    Article  CAS  PubMed  Google Scholar 

  • Mancuso M, Filosto M, Bellan M, Liguori R, Montagna P, Baruzzi A, DiMauro S, Carelli V (2004) POLG mutations causing ophthalmoplegia, sensorimotor polyneuropathy, ataxia, and deafness. Neurology 62:316–318

    Article  CAS  PubMed  Google Scholar 

  • Mari M, Morales A, Colell A et al (2009) Mitochondrial glutathione, a key survival antioxidant. Antioxid Redox Signal 11(11):2685–2700

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Mattiasson G, Shamloo M, Gido G, Mathi K, Tomasevic G, Yi S, Warden CH, Castilho RF, Melcher T, Gonzalez-Zulueta M, Nikolich K, Wieloch T (2003) Uncoupling protein-2 prevents neuronal death and diminishes brain dysfunction after stroke and brain trauma. Nat Med 9(8):1062–1068

    Article  CAS  PubMed  Google Scholar 

  • Mattson MP (2000) Apoptosis in neurodegenerative disorders. Nat Rev Mol Cell Biol 1(2):120–129

    Article  CAS  PubMed  Google Scholar 

  • McFadden SL, Ding D, Reaume AG et al (1999) Age-related cochlear hair cell loss is enhanced in mice lacking copper/zinc superoxide dismutase. Neurobiol Aging 20(1):1–8

    Article  CAS  PubMed  Google Scholar 

  • Montoya J, Lopez-Perez MJ, Ruiz-Pesini E (2006) Mitochondrial DNA transcription and diseases: past, present and future. Biochim Biophys Acta 1757(9-10):1179–1189

    Google Scholar 

  • Nguyen KV, Ostergaard E, Ravn SH, Balslev T, Danielsen ER, Vardag A, McKiernan PJ, Gray G, Naviaux RK (2005) POLG mutations in Alpers syndrome. Neurology 65(9):1493–1495

    Google Scholar 

  • Niu X, Trifunovic A, Larsson NG, Canlon B (2007) Somatic mtDNA mutations cause progressive hearing loss in the mouse. Exp Cell Res 313(18):3924–3934

    Article  CAS  PubMed  Google Scholar 

  • Ohlemiller KK, Wright JS, Dugan LL (1999) Early elevation of cochlear reactive oxygen species following noise exposure. Audiol Neurootol 4(5):229–236

    Article  CAS  PubMed  Google Scholar 

  • Ohlemiller KK, McFadden SL, Ding DL et al (2000) Targeted mutation of the gene for cellular glutathione peroxidase (Gpx1) increases noise-induced hearing loss in mice. J Assoc Res Otolaryngol 1(3):243–254

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Palaniappan AR, Dai A (2007) Mitochondrial ageing and the beneficial role of alpha-lipoic acid. Neurochem Res 32:1552–1558

    Article  CAS  PubMed  Google Scholar 

  • Perry TL, Yong VW (1986) Idiopathic Parkinson’s disease, progressive supranuclear palsy and glutathione metabolism in the substantia nigra of patients. Neurosci Lett 67(3):269–274

    Article  CAS  PubMed  Google Scholar 

  • Raimundo N, Baysal BE, Shadel GS (2011) Revisiting the TCA cycle: signaling to tumor formation. Trends Mol Med 17(11):641–649

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Rebrin I, Sohal RS (2008) Pro-oxidant shift in glutathione redox state during aging. Adv Drug Deliv Rev 60:1545–1552

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Ribas V, Garcia-Ruiz C, Fernandez-Checa JC (2014) Glutathione and mitochondria. Front Pharmacol 5:151

    Google Scholar 

  • Schriner SE, Linford NJ, Martin GM et al (2005) Extension of murine life span by overexpression of catalase targeted to mitochondria. Science 308:1909–1911

    Article  CAS  PubMed  Google Scholar 

  • Shigenaga MK, Hagen TM, Ames BN (1994) Oxidative damage and mitochondrial decay in aging. Proc Natl Acad Sci USA 91(23):10771–10778

    Google Scholar 

  • Someya S, Prolla TA (2010) Mitochondrial oxidative damage and apoptosis in age-related hearing loss. Mech Ageing Dev 131(7–8):480–486

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Someya S, Yamasoba T, Kujoth GC, Pugh TD, Weindruch R, Tanokura M, Prolla TA (2008) The role of mtDNA mutations in the pathogenesis of age-related hearing loss in mice carrying a mutator DNA polymerase gamma. Neurobiol Aging 29:1080–1092

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Someya S, Xu J, Kondo K, Ding D, Salvi RJ, Yamasoba T, Rabinovitch PS, Weindruch R, Leeuwenburgh C, Tanokura M, Prolla TA (2009) Age-related hearing loss in C57BL/6J mice is mediated by Bak-dependent mitochondrial apoptosis. Proc Natl Acad Sci USA 106(46):19432–19437

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Someya S, Yu W, Hallows WC, Xu J, Vann JM, Leeuwenburgh C, Tanokura M, Denu JM, Prolla TA (2010) Sirt3 mediates reduction of oxidative damage and prevention of age-related hearing loss under caloric restriction. Cell 143(5):802–812

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Sugiura S, Uchida Y, Nakashima T, Ando F, Shimokata H (2010) The association between gene polymorphisms in uncoupling proteins and hearing impairment in Japanese elderly. Acta Otolaryngol 130(4):487–492

    Article  CAS  PubMed  Google Scholar 

  • Sun J, Folk D, Bradley TJ, Tower J (2002) Induced overexpression of mitochondrial Mn-superoxide dismutase extends the life span of adult Drosophila melanogaster. Genetics 161:661–672

    CAS  PubMed Central  PubMed  Google Scholar 

  • Trifunovic A, Wredenberg A, Falkenberg M, Spelbrink JN, Rovio AT, Bruder CE, Bohlooly-Y M, Gidlöf S, Oldfors A, Wibom R, Törnell J, Jacobs HT, Larsson NG (2004) Premature ageing in mice expressing defective mitochondrial DNA polymerase. Nature 429(6990):417–423

    Article  CAS  PubMed  Google Scholar 

  • Van Eyken E, Van Camp G, Fransen E, Topsakal V, Hendrickx JJ, Demeester K, Van de Heyning P, Maki-Torkko E, Hannula S, Sorri M, Jensen M, Parving A, Bille M, Baur M, Pfister M, Bonaconsa A, Mazzoli M, Orzan E, Espeso A, Stephens D, Verbruggen K, Huyghe J, Dhooge I, Huygen P, Kremer H, Cremers CW, Kunst S, Manninen M, Pyykko I, Lacava A, Steffens M, Wienker TF, Van Laer L (2007) Contribution of the N-acetyltransferase 2 polymorphism NAT2*6A to age-related hearing impairment. J Med Genet 44(9):570–578

    Article  PubMed Central  PubMed  Google Scholar 

  • Wallace DC (2005) A mitochondrial paradigm of metabolic and degenerative diseases, aging, and cancer: a dawn for evolutionary medicine. Annu Rev Genet 39:359–407

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • West AP, Shadel GS, Ghosh S (2011) Mitochondria in innate immune responses. Nat Rev Immunol 11:389–402

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Wong PC, Pardo CA, Borchelt DR, Lee MK, Copeland NG, Jenkins NA, Sisodia SS, Cleveland DW, Price DL (1995) An adverse property of a familial ALS-linked SOD1 mutation causes motor neuron disease characterized by vacuolar degeneration of mitochondria. Neuron 14(6):1105–1116

    Article  CAS  PubMed  Google Scholar 

  • Yamasoba T, Lin FR, Someya S, Kashio A, Sakamoto T, Kondo K (2013) Current concepts in age-related hearing loss: epidemiology and mechanistic pathways. Hear Res 303:30–38

    Google Scholar 

  • Yildirim I, Kilinc M, Okur E, Inanc Tolun F, Kilic MA, Kurutas EB, Ekerbicer HC (2007) The effects of noise on hearing and oxidative stress in textile workers. Ind Health 45(6):743–749

    Article  PubMed  Google Scholar 

  • Yoshida T, Oka S, Masutani H, Nakamura H, Yodoi J (2003) The role of thioredoxin in the aging process: involvement of oxidative stress. Antioxid Redox Signal 5(5):563–770

    Article  CAS  PubMed  Google Scholar 

  • Youle RJ, Strasser A (2008) The BCL-2 protein family: opposing activities that mediate cell death. Nat Rev Mol Cell Biol 9:47–59

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Aging and Geriatric Research, University of Florida, Gainesville, FL, 32610, USA

    Mi-Jung Kim, Karessa White, Logan Walker, Chul Han & Shinichi Someya

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  1. Mi-Jung Kim
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  2. Karessa White
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  3. Logan Walker
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  4. Chul Han
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  5. Shinichi Someya
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Correspondence to Shinichi Someya .

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Editors and Affiliations

  1. Cochlear Signaling & Tissue Engin., University of Michigan Kresge Hearing Research Institute, Ann Arbor, Michigan, USA

    Josef Miller

  2. Dept of Speech , Lang & Hearing Sci, Univ of Florida Health Sciences Center, Gainesville, Florida, USA

    Colleen G. Le Prell

  3. Div . of Otolaryngology Head & Neck Surgery, SIU School of Medicine, Springfield, Illinois, USA

    Leonard Rybak

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Kim, MJ., White, K., Walker, L., Han, C., Someya, S. (2015). Age-Related Hearing Loss: Mitochondrial Biochemical Pathways and Molecular Targets. In: Miller, J., Le Prell, C., Rybak, L. (eds) Free Radicals in ENT Pathology. Oxidative Stress in Applied Basic Research and Clinical Practice. Humana Press, Cham. https://doi.org/10.1007/978-3-319-13473-4_13

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