Age-related hearing loss: An updated and comprehensive review of the interventions

Document Type : Review Article


1 Department of Audiology, School of Rehabilitation, Tehran University of Medical Sciences, Tehran, Iran

2 Department of Audiology, School of Rehabilitation, Isfahan University of Medical Sciences, Isfahan, Iran

3 Otolaryngology Research Center, Amiralam Hospital, Tehran University of Medical Sciences, Tehran, Iran


Aging causes progressive degenerative changes in many organs, particularly the auditory system. Several attempts have been conducted to investigate preventive and therapeutic strategy/strategies for age-related auditory dysfunction, such as maintaining a healthy lifestyle through good nutrition, lower anxiety levels, and noise exposure, different pharmacological approaches, gene and cell therapy, and other strategies. However, it is not clear which approach is the best to slow down these dysfunctions because several different underlying mechanistic pathways are associated with presbycusis which eventually leads to different types of this disease. A combination of several methods is probably required, whereas the effectiveness for some people needs to be monitored. The effectiveness of treatments will not be the same for all; therefore, we may need to have a unique and personalized approach to the prevention and treatment of ARHL for each person. In addition, each method needs to specify what type of presbycusis can prevent or treat and provide complete information about the extent, duration of treatment, persistency of treatment, side effects, and whether the approach is for treatment or prevention or even both. This paper reviews the updated literature, which targets current interventions for age-related hearing loss. 


Main Subjects

1. Seidman MD, Ahmad N, Bai U. Molecular mechanisms of age-related hearing loss. Ageing Res Rev 2002; 1:331-343.
2. Gates GA, Mills JH. Presbycusis. Lancet 2005; 366:1111-1120.
3. Someya S, Prolla TA. Mitochondrial oxidative damage and apoptosis in age-related hearing loss. Mech Ageing Dev 2010; 131:480-486.
4. Fetoni AR, Picciotti PM, Paludetti G, Troiani D. Pathogenesis of presbycusis in animal models: a review. Exp Gerontol 2011; 46:413-425.
5. Heman-Ackah SE, Juhn SK, Huang TC, Wiedmann TS. A combination antioxidant therapy prevents age-related hearing loss in C57BL/6 mice. Otolaryngol Head Neck Surg 2010; 143:429-434.
6. Someya S, Tanokura M, Weindruch R, Prolla TA, Yamasoba T. Effects of caloric restriction on age-related hearing loss in rodents and rhesus monkeys. Curr Aging Sci 2010; 3:20-25.
7. Bielefeld EC, Tanaka C, Chen GD, Henderson D. Age-related hearing loss: is it a preventable condition? Hear Res 2010; 264:98-107.
8. Mehta KM, Simonsick EM, Penninx BW, Schulz R, Rubin SM, Satterfield S, et al. Prevalence and correlates of anxiety symptoms in well-functioning older adults: findings from the health aging and body composition study. J Am Geriatr Soc 2003; 51:499-504.
9. Jayakody DMP, Almeida OP, Speelman CP, Bennett RJ, Moyle TC, Yiannos JM, et al. Association between speech and high-frequency hearing loss and depression, anxiety and stress in older adults. Maturitas 2018; 110:86-91.
10. Jayakody DMP, Friedland PL, Eikelboom RH, Martins RN, Sohrabi HR. A novel study on association between untreated hearing loss and cognitive functions of older adults: baseline non-verbal cognitive assessment results. Clin Otolaryngol 2018; 43:182-191.
11. Contrera KJ, Betz J, Deal J, Choi JS, Ayonayon HN, Harris T, et al. Association of hearing impairment and anxiety in older adults. J Aging Health 2017; 29:172-184.
12. Rodrigo L, Campos-Asensio C, Rodríguez M, Crespo I, Olmedillas H. Role of nutrition in the development and prevention of age-related hearing loss: a scoping review. J Formos Med Assoc 2021; 120:107-120.
13. Sardone R, Lampignano L, Guerra V, Zupo R, Donghia R, Castellana F, et al. Relationship between inflammatory food consumption and age-related hearing loss in a prospective observational cohort: results from the salus in apulia study. Nutrients 2020; 12:426-440.
14. Gopinath B, Flood VM, McMahon CM, Burlutsky G, Brand-Miller J, Mitchell P. Dietary glycemic load is a predictor of age-related hearing loss in older adults. J Nutr 2010; 140:2207-2212.
15. Curhan SG, Eavey R, Shargorodsky J, Curhan GC. Analgesic use and the risk of hearing loss in men. Am J Med 2010; 123:231-237.
16. Kim S, Park JM, Han JS, Seo JH, Han K-D, Joo YH, et al. Age-related hearing loss in the korea national health and nutrition examination survey. PLoS One 2020; 15:1-9.
17. Kim TS, Chung JW. Associations of dietary riboflavin, niacin, and retinol with age-related hearing loss: an analysis of korean national health and nutrition examination survey data. Nutrients 2019; 11:896-909.
18. Lasisi AO, Fehintola FA. Correlation between plasma levels of radical scavengers and hearing threshold among elderly subjects with age-related hearing loss. Acta Otolaryngol 2011; 131:1160-1164.
19. Michikawa T, Nishiwaki Y, Kikuchi Y, Hosoda K, Mizutari K, Saito H, et al. Serum levels of retinol and other antioxidants for hearing impairment among Japanese older adults. J Gerontol A Biol Sci Med Sci 2009; 64:910-915.
20. Kang JW, Choi HS, Kim K, Choi JY. Dietary vitamin intake correlates with hearing thresholds in the older population: the korean national health and nutrition examination survey. Am J Clin Nutr 2014; 99:1407-1413.
21. Spankovich C, Hood LJ, Silver HJ, Lambert W, Flood VM, Mitchell P. Associations between diet and both high and low pure tone averages and transient evoked otoacoustic emissions in an older adult population-based study. J Am Acad Audiol 2011; 22:49-58.
22. Gopinath B, Flood VM, McMahon CM, Burlutsky G, Spankovich C, Hood LJ, et al. Dietary antioxidant intake is associated with the prevalence but not incidence of age-related hearing loss. J Nutr Health Aging 2011; 15:896-900.
23. Lasisi TJ, Lasisi AO. Evaluation of serum antioxidants in age-related hearing loss. Aging Clin Exp Res 2015; 27:265-269.
24. Houston DK, Johnson MA, Nozza RJ, Gunter EW, Shea KJ, Cutler GM, et al. Age-related hearing loss, vitamin B-12, and folate in elderly women. Am J Clin Nutr 1999; 69:564-571.
25. Lasisi AO, Fehintola FA, Yusuf OB. Age-related hearing loss, vitamin B12, and folate in the elderly. Otolaryngol Head Neck Surg 2010; 143:826-830.
26. Gopinath B, Flood VM, Rochtchina E, McMahon CM, Mitchell P. Serum homocysteine and folate concentrations are associated with prevalent age-related hearing loss. J Nutr 2010; 140:1469-1474.
27. Durga J, Anteunis LJ, Schouten EG, Bots ML, Kok FJ, Verhoef P. Association of folate with hearing is dependent on the 5,10-methylenetetrahdyrofolate reductase 677C-->T mutation. Neurobiol Aging 2006; 27:482-489.
28. Berner B. Age-related hearing impairment and B vitamin status. Acta Otolaryngol 2000; 120:633-637.
29. Park S, Johnson MA, Shea-Miller K, Chicchis ARD, Allen RH, Stabler SP. Age-related hearing loss, methylmalonic acid, and vitamin B12 status in older adults. J Nutr Elder 2007; 25:105-120.
30. Mills JH, Matthews LJ, Lee FS, Dubno JR, Schulte BA, Weber PC. Gender-specific effects of drugs on hearing levels of older persons. Ann N Y Acad Sci 1999; 884:381-388.
31. Gopinath B, Flood VM, Teber E, McMahon CM, Mitchell P. Dietary intake of cholesterol is positively associated and use of cholesterol-lowering medication is negatively associated with prevalent age-related hearing loss. J Nutr 2011; 141:1355-1361.
32. Gopinath B, Flood VM, Rochtchina E, McMahon CM, Mitchell P. Consumption of omega-3 fatty acids and fish and risk of age-related hearing loss. Am J Clin Nutr 2010; 92:416-421.
33. Guimaraes P, Frisina ST, Mapes F, Tadros SF, Frisina DR, Frisina RD. Progestin negatively affects hearing in aged women. Proc Nat Acad Sci 2006; 103:14246-14249.
34. Curhan SG, Eliassen AH, Eavey RD, Wang M, Lin BM, Curhan GC. Menopause and postmenopausal hormone therapy and risk of hearing loss. Menopause 2017; 24:1049-1056.
35. Hederstierna C, Hultcrantz M, Collins A, Rosenhall U. Hearing in women at menopause. Prevalence of hearing loss, audiometric configuration and relation to hormone replacement therapy. Acta Otolaryngol 2007; 127:149-155.
36. Kilicdag EB, Yavuz H, Bagis T, Tarim E, Erkan AN, Kazanci F. Effects of estrogen therapy on hearing in postmenopausal women. Am J Obstet Gynecol 2004; 190:77-82.
37. Tadros SF, Frisina ST, Mapes F, Frisina DR, Frisina RD. Higher serum aldosterone correlates with lower hearing thresholds: a possible protective hormone against presbycusis. Hear Res 2005; 209:10-18.
38. Dullemeijer C, Verhoef P, Brouwer IA, Kok FJ, Brummer RJ, Durga J. Plasma very long-chain n-3 polyunsaturated fatty acids and age-related hearing loss in older adults. J Nutr Health Aging 2010; 14:347-351.
39. Ciorba A, Hatzopoulos S, Bianchini C, Aimoni C, Skarzynski H, Skarzynski PH. Genetics of presbycusis and presbystasis. Int J Immunopathol Pharmacol 2015; 28:29-35.
40. Bouzid A, Smeti I, Chakroun A, Loukil S, Gibriel AA, Grati M, et al. CDH23 methylation status and presbycusis risk in elderly women. Front Aging Neurosci 2018; 10:241-248.
41. Kidd Iii AR, Bao J. Recent advances in the study of age-related hearing loss: a mini-review. Gerontology 2012; 58:490-496.
42. Seidman MD. Effects of dietary restriction and antioxidants on presbyacusis. Laryngoscope 2000; 110:727-738.
43. Han C, Someya S. Maintaining good hearing: calorie restriction, Sirt3, and glutathione. Exp Gerontol 2013; 48:1091-1095.
44. Someya S, Yamasoba T, Weindruch R, Prolla TA, Tanokura M. Caloric restriction suppresses apoptotic cell death in the mammalian cochlea and leads to prevention of presbycusis. Neurobiol Aging 2007; 28:1613-1622.
45. Mannstrom P, Ulfhake B, Kirkegaard M, Ulfendahl M. Dietary restriction reduces age-related degeneration of stria vascularis in the inner ear of the rat. Exp Gerontol 2013; 48:1173-1179.
46. Henry KR. Effects of dietary restriction on presbyacusis in the mouse. Audiology 1986; 25:329-337.
47. Fowler CG, Torre P 3rd, Kemnitz JW. Effects of caloric restriction and aging on the auditory function of rhesus monkeys (Macaca mulatta): the university of wisconsin study. Hear Res 2002; 169:24-35.
48. Fowler CG, Chiasson KB, Leslie TH, Thomas D, Beasley TM, Kemnitz JW, et al. Auditory function in rhesus monkeys: effects of aging and caloric restriction in the Wisconsin monkeys five years later. Hear Res 2010; 261:75-81.
49. Torre P 3rd, Mattison JA, Fowler CG, Lane MA, Roth GS, Ingram DK. Assessment of auditory function in rhesus monkeys (Macaca mulatta): effects of age and calorie restriction. Neurobiol Aging 2004; 25:945-954.
50. Du Z, Yang Y, Hu Y, Sun Y, Zhang S, Peng W, et al. A long-term high-fat diet increases oxidative stress, mitochondrial damage and apoptosis in the inner ear of D-galactose-induced aging rats. Hear Res 2012; 287:15-24.
51. Sweet RJ, Price JM, Henry KR. Dietary restriction and presbyacusis: periods of restriction and auditory threshold losses in the CBA/J mouse. Audiology 1988; 27:305-312.
52. Willott JF, Erway LC, Archer JR, Harrison DE. Genetics of age-related hearing loss in mice. II. strain differences and effects of caloric restriction on cochlear pathology and evoked response thresholds. Hear Res 1995; 88:143-155.
53. Someya S, Yu W, Hallows WC, Xu J, Vann JM, Leeuwenburgh C, et al. Sirt3 mediates reduction of oxidative damage and prevention of age-related hearing loss under caloric restriction. Cell 2010; 143:802-812.
54. Takumida M, Anniko M. Radical scavengers: a remedy for presbyacusis. A pilot study. Acta Otolaryngol 2005; 125:1290-1295.
55. Salami A, Mora R, Dellepiane M, Manini G, Santomauro V, Barettini L, et al. Water-soluble coenzyme Q10 formulation (Q-TER((R))) in the treatment of presbycusis. Acta Otolaryngol 2010; 130:1154-1162.
56. Müderris T, Sevil E, Yar Sağlam AS, Babademez MA. Coenzyme q10 effectively prevents age-related hearing loss in c57bl/6 mice. Turk Geriatri Dergisi 2021; 24:235-243.
57. Peng W, Hu Y, Zhong Y, Chen B, Sun Y, Yang Y, et al. Protective roles of alpha-lipoic acid in rat model of mitochondrial DNA4834bp deletion in inner ear. J Huazhong Univ Sci Technolog Med Sci 2010; 30:514-518.
58. Someya S, Xu J, Kondo K, Ding D, Salvi RJ, Yamasoba T, et al. Age-related hearing loss in C57BL/6J mice is mediated by Bak-dependent mitochondrial apoptosis. Proc Natl Acad Sci U S A 2009; 106:19432-19437.
59. Le T, Keithley EM. Effects of antioxidants on the aging inner ear. Hear Res 2007; 226:194-202.
60. Durga J, Verhoef P, Anteunis LJ, Schouten E, Kok FJ. Effects of folic acid supplementation on hearing in older adults: a randomized, controlled trial. Ann Intern Med 2007; 146:1-9.
61. Alvarado JC, Fuentes-Santamaria V, Melgar-Rojas P, Valero ML, Gabaldon-Ull MC, Miller JM, et al. Synergistic effects of free radical scavengers and cochlear vasodilators: a new otoprotective strategy for age-related hearing loss. Front Aging Neurosci 2015; 7:86-93.
62. Ding D, Jiang H, Chen GD, Longo-Guess C, Muthaiah VP, Tian C, et al. N-acetyl-cysteine prevents age-related hearing loss and the progressive loss of inner hair cells in gamma-glutamyl transferase 1 deficient mice. Aging (Albany NY) 2016; 8:730-750.
63. Davis RR, Kuo MW, Stanton SG, Canlon B, Krieg E, Alagramam KN. N-acetyl L-cysteine does not protect against premature age-related hearing loss in C57BL/6J mice: a pilot study. Hear Res 2007; 226:203-208.
64. Seidman MD, Khan MJ, Tang WX, Quirk WS. Influence of lecithin on mitochondrial DNA and age-related hearing loss. Otolaryngol Head Neck Surg 2002; 127:138-144.
65. Sanz-Fernandez R, Sanchez-Rodriguez C, Granizo JJ, Durio-Calero E, Martin-Sanz E. Accuracy of auditory steady state and auditory brainstem responses to detect the preventive effect of polyphenols on age-related hearing loss in Sprague-Dawley rats. Eur Arch Otorhinolaryngol 2016; 273:341-347.
66. Derin A, Agirdir B, Derin N, Dinc O, Guney K, Ozcaglar H, et al. The effects of L-carnitine on presbyacusis in the rat model. Clin Otolaryngol Allied Sci 2004; 29:238-241.
67. Romeo G, Giorgetti M. Therapeutic effects of vitamin A associated with vitamin E in perceptual hearing loss. Acta Vitaminol Enzymol 1985; 7:139-143.
68. Bielefeld EC, Coling D, Chen GD, Henderson D. Multiple dosing strategies with acetyl L-carnitine (ALCAR) fail to alter age-related hearing loss in the Fischer 344/NHsd rat. J Negat Results Biomed 2008; 7:4-9.
69. Kashio A, Amano A, Kondo Y, Sakamoto T, Iwamura H, Suzuki M, et al. Effect of vitamin C depletion on age-related hearing loss in SMP30/GNL knockout mice. Biochem Biophys Res Commun 2009; 390:394-398.
70. Sha SH, Kanicki A, Halsey K, Wearne KA, Schacht J. Antioxidant-enriched diet does not delay the progression of age-related hearing loss. Neurobiol Aging 2012; 33:1010-1013.
71. Polanski JF, Cruz OL. Evaluation of antioxidant treatment in presbyacusis: prospective, placebo-controlled, double-blind, randomised trial. J Laryngol Otol 2013; 127:134-141.
72. Ahn JH, Kang HH, Kim TY, Shin JE, Chung JW. Lipoic acid rescues DBA mice from early-onset age-related hearing impairment. Neuroreport 2008; 19:1265-1269.
73. Sanchez-Rodriguez C, Cuadrado E, Riestra-Ayora J, Sanz-Fernandez R. Polyphenols protect against age-associated apoptosis in female rat cochleae. Biogerontology 2018; 19:159-169.
74. Marie A, Meunier J, Brun E, Malmstrom S, Baudoux V, Flaszka E, et al. N-acetylcysteine treatment reduces age-related hearing loss and memory impairment in the senescence-accelerated prone 8 (SAMP8) mouse model. Aging Dis 2018; 9:664-673.
75. Serra LSM, Araújo JG, Vieira ALS, Silva EMD, Andrade RR, Kückelhaus SAS, et al. Role of melatonin in prevention of age-related hearing loss. PLoS One 2020; 15:1-9.
76. Szepesy J, Humli V, Farkas J, Miklya I, Tímár J, Tábi T, et al. Chronic oral selegiline treatment mitigates age-related hearing loss in BALB/c mice. Int J Mol Sci 2021; 22:2853-2870.
77. Sánchez-Rodríguez C, Martín-Sanz E, Cuadrado E, Granizo JJ, Sanz-Fernández R. Protective effect of polyphenols on presbycusis via oxidative/nitrosative stress suppression in rats. Exp Gerontol 2016; 83:31-36.
78. Salam SA, Mostafa F, Alnamshan MM, Elshewemi SS, Sorour JM. Thymoquinone ameliorates age-related hearing loss in C57BL/6J mice by modulating Sirt1 activity and Bak1 expression. Biomed Pharmacother 2021; 143:112149-112158.
79. Monge Naldi A, Belfrage C, Jain N, Wei ET, Canto Martorell B, Gassmann M, et al. Neuronal erythropoietin overexpression protects mice against age-related hearing loss (presbycusis). Neurobiol Aging 2015; 36:3278-3287.
80. Hoshino T, Tabuchi K, Nishimura B, Tanaka S, Nakayama M, Ishii T, et al. Protective role of Nrf2 in age-related hearing loss and gentamicin ototoxicity. Biochem Biophys Res Commun 2011; 415:94-98.
81. Hu H, Ma Y, Ye B, Wang Q, Yang T, Lv J, et al. The role of Efr3a in age-related hearing loss. Neuroscience 2017; 341:1-8.
82. Wang J, Menchenton T, Yin S, Yu Z, Bance M, Morris DP, et al. Over-expression of X-linked inhibitor of apoptosis protein slows presbycusis in C57BL/6J mice. Neurobiol Aging 2010; 31:1238-1249.
83. Han F, Yu H, Tian C, Chen HE, Benedict-Alderfer C, Zheng Y, et al. A new mouse mutant of the Cdh23 gene with early-onset hearing loss facilitates evaluation of otoprotection drugs. Pharmacogenomics J 2012; 12:30-44.
84. Han F, Yu H, Zheng T, Ma X, Zhao X, Li P, et al. Otoprotective effects of erythropoietin on Cdh23erl/erl mice. Neuroscience 2013; 237:1-6.
85. Han X, Ge R, Xie G, Li P, Zhao X, Gao L, et al. Caspase-mediated apoptosis in the cochleae contributes to the early onset of hearing loss in A/J mice. ASN Neuro 2015; 7:1-13.
86. Yang L, Zhang H, Han X, Zhao X, Hu F, Li P, et al. Attenuation of hearing loss in DBA/2J mice by anti-apoptotic treatment. Hear Res 2015; 327:109-116.
87. Hu J, Xu M, Yuan J, Li B, Entenman S, Yu H, et al. Tauroursodeoxycholic acid prevents hearing loss and hair cell death in Cdh23(erl/erl) mice. Neuroscience 2016; 316:311-320.
88. Mikuriya T, Sugahara K, Sugimoto K, Fujimoto M, Takemoto T, Hashimoto M, et al. Attenuation of progressive hearing loss in a model of age-related hearing loss by a heat shock protein inducer, geranylgeranylacetone. Brain Res 2008; 1212:9-17.
89. Lee YY, Gil ES, Jeong IH, Kim H, Jang JH, Choung Y-H. Heat shock factor 1 prevents age-related hearing loss by decreasing endoplasmic reticulum stress. Cells 2021; 10:2454-2471.
90. Rousset F, Nacher-Soler G, Coelho M, Ilmjarv S, Kokje VBC, Marteyn A, et al. Redox activation of excitatory pathways in auditory neurons as mechanism of age-related hearing loss. Redox Biol 2020; 30:101434-101448.
91. Bermúdez-Muñoz JM, Celaya AM, Hijazo-Pechero S, Wang J, Serrano M, Varela-Nieto I. G6PD overexpression protects from oxidative stress and age-related hearing loss. Aging Cell  2020; 19:1-18.
92. Oishi T, Matsumaru D, Ota N, Kitamura H, Zhang T, Honkura Y, et al. Activation of the NRF2 pathway in Keap1-knockdown mice attenuates progression of age-related hearing loss. NPJ Aging Mech Dis 2020; 6:14-29.
93. Xiong H, Chen S, Lai L, Yang H, Xu Y, Pang J, et al. Modulation of miR-34a/SIRT1 signaling protects cochlear hair cells against oxidative stress and delays age-related hearing loss through coordinated regulation of mitophagy and mitochondrial biogenesis. Neurobiol Aging 2019; 79:30-42.
94. Muderris T, Yar Sağlam AS, Unsal D, Mülazimoğlu S, Sevil E, Kayhan H. Efficiency of resveratrol in the prevention and treatment of age‑related hearing loss. Exp Ther Med 2022; 23:40-47.
95. Li H, Lu M, Zhang H, Wang S, Wang F, Ma X, et al. Downregulation of REST in the cochlea contributes to age-related hearing loss via the p53 apoptosis pathway. Cell Death Dis 2022; 13:343-357.
96. Cassinotti LR, Ji L, Borges BC, Cass ND, Desai AS, Kohrman DC, et al. Cochlear neurotrophin-3 overexpression at mid-life prevents age-related cochlear synaptopathy and slows age-related hearing loss. bioRxiv 2022: 21:1-11.
97. Li Q, Zang Y, Sun Z, Zhang W, Liu H. Long noncoding RNA Gm44593 attenuates oxidative stress from age-related hearing loss by regulating miR-29b/WNK1. Bioengineered 2022; 13:573-582.
98. Ren H, Chen J, Wang Y, Zhang S, Zhang B. Intracerebral neural stem cell transplantation improved the auditory of mice with presbycusis. Int J Clin Exp Pathol 2013; 6:230-241.
99. Johnson KR, Tian C, Gagnon LH, Jiang H, Ding D, Salvi R. Effects of Cdh23 single nucleotide substitutions on age-related hearing loss in C57BL/6 and 129S1/Sv mice and comparisons with congenic strains. Sci Rep 2017; 7:44450-44463.
100. Yu YF, Wu WY, Xiao GS, Shi J, Ling HY. Effect of T-type calcium channel blockers on spiral ganglion neurons of aged C57BL/6J mice. Int J Clin Exp Med 2015; 8:15466-15473.
101. Yu YF, Wu WY, Xiao GS, Ling HY, Pan C. Protection of the cochlear hair cells in adult C57BL/6J mice by T-type calcium channel blockers. Exp Ther Med 2016; 11:1039-1144.
102. Lei D, Gao X, Perez P, Ohlemiller KK, Chen CC, Campbell KP, et al. Anti-epileptic drugs delay age-related loss of spiral ganglion neurons via T-type calcium channel. Hear Res 2011; 278:106-112.
103. Syka J, Ouda L, Nachtigal P, Solichova D, Semecky V. Atorvastatin slows down the deterioration of inner ear function with age in mice. Neurosci Lett 2007; 411:112-116.
104. Vlajkovic SM, Guo CX, Telang R, Wong AC, Paramananthasivam V, Boison D, et al. Adenosine kinase inhibition in the cochlea delays the onset of age-related hearing loss. Exp Gerontol 2011; 46:905-914.
105. Shin M, Pandya M, Espinosa K, Telang R, Boix J, Thorne PR, et al. Istradefylline mitigates age-related hearing loss in C57BL/6J mice. Int J Mol Sci 2021; 22:8000-8014.
106. Chen GD, Kermany MH, D’Elia A, Ralli M, Tanaka C, Bielefeld EC, et al. Too much of a good thing: long-term treatment with salicylate strengthens outer hair cell function but impairs auditory neural activity. Hear Res 2010; 265:63-69.
107. Altschuler RA, Kanicki A, Martin C, Kohrman DC, Miller RA. Rapamycin but not acarbose decreases age-related loss of outer hair cells in the mouse Cochlea. Hear Res 2018; 370:11-15.
108. Altschuler RA, Kabara L, Martin C, Kanicki A, Stewart CE, Kohrman DC, et al. Rapamycin added to diet in late mid-life delays age-related hearing loss in UMHET4 mice. Front Cell Neurosci 2021; 15:1-7.
109. Fu X, Sun X, Zhang L, Jin Y, Chai R, Yang L, et al. Tuberous sclerosis complex–mediated mTORC1 overactivation promotes age-related hearing loss. J Clin Invest 2018; 128:4938-4955.
110. Liu H, Li F, Li X, Wu Q, Dai C. Rapamycin ameliorates age-related hearing loss in C57BL/6J mice by enhancing autophagy in the SGNs. Neurosci Lett 2022; 772:136493.
111. Frisina RD, Ding B, Zhu X, Walton JP. Age-related hearing loss: prevention of threshold declines, cell loss and apoptosis in spiral ganglion neurons. Aging (Albany NY) 2016; 8:2081-2099.
112. Halonen J, Hinton AS, Frisina RD, Ding B, Zhu X, Walton JP. Long-term treatment with aldosterone slows the progression of age-related hearing loss. Hear Res 2016; 336:63-71.
113. Williamson TT, Ding B, Zhu X, Frisina RD. Hormone replacement therapy attenuates hearing loss: mechanisms involving estrogen and the IGF-1 pathway. Aging Cell 2019; 18:1-15.
114. Price K, Zhu X, Guimaraes PF, Vasilyeva ON, Frisina RD. Hormone replacement therapy diminishes hearing in peri-menopausal mice. Hear Res 2009; 252:29-36.
115. Chen L, Yang YQ, Feng ZY, Li XR, Han ZW, Ma KT, et al. Effects of estrogen on apoptosis of spiral ganglion cells in cochlea of aged C57BL/6J mice]. Zhongguo Ying Yong Sheng Li Xue Za Zhi 2020; 36:529-533.
116. Tanaka C, Bielefeld EC, Chen GD, Li M, Henderson D. Ameliorative effects of an augmented acoustic environment on age-related hearing loss in middle-aged Fischer 344/NHsd rats. Laryngoscope 2009; 119:1374-1379.
117. Willott JF, Turner JG. Prolonged exposure to an augmented acoustic environment ameliorates age-related auditory changes in C57BL/6J and DBA/2J mice. Hear Res 1999; 135:78-88.
118. Willott JF, Turner JG, Sundin VS. Effects of exposure to an augmented acoustic environment on auditory function in mice: roles of hearing loss and age during treatment. Hear Res 2000; 142:79-88.
119. Brecht EJ, Barsz K, Gross B, Walton JP. Increasing GABA reverses age-related alterations in excitatory receptive fields and intensity coding of auditory midbrain neurons in aged mice. Neurobiol Aging 2017; 56:87-99.
120. Friedman; Rick (Pacific Palisades C, Vollrath; Benedikt (San Diego, CA), inventor; House Ear Institute (Los Angeles, CA), assignee. Treatment and/or Prevention of Presbycusis by Modulation of Metabotropic Glutamate Receptor 7. United States of America patent 9,173,864. 2015 November 3, 2015.
121. Boettcher FA, Mills JH, Norton BL, Schmiedt RA. Age-related changes in auditory evoked potentials of gerbils. II. response latencies. Hear Res 1993; 71:146-156.
122. Han C, Ding D, Lopez MC, Manohar S, Zhang Y, Kim MJ, et al. Effects of long-term exercise on age-related hearing loss in mice. J Neurosci 2016; 36:11308-11319.
123. Boero LE, Castagna VC, Terreros G, Moglie MJ, Silva S, Maass JC, et al. Preventing presbycusis in mice with enhanced medial olivocochlear feedback. Proc Natl Acad Sci U S A 2020; 117:11811-11819.
124. Ter Haar G, Mulder JJ, Venker-van Haagen AJ, van Sluijs FJ, Snik AF, Smoorenburg GF. Treatment of age-related hearing loss in dogs with the vibrant soundbridge middle ear implant: short-term results in 3 dogs. J Vet Intern Med 2010; 24:557-564.
125. Miwa T. Protective effects of N1-methylnicotinamide against high-fat diet- and age-induced hearing loss via moderate overexpression of sirtuin 1 protein. Front Cell Neurosci 2021; 15:1-12.
126. Fujita T, Yamashita D, Uehara N, Inokuchi G, Hasegawa S, Otsuki N, et al. A high-fat diet delays age-related hearing loss progression in C57BL/6J mice. PLoS One 2015; 10:1-11.
127. Tavanai E, Mohammadkhani G. Role of antioxidants in prevention of age-related hearing loss: a review of literature. Eur Arch Otorhinolaryngol 2017; 274:1821-1834.
128. Mohammadkhani G, Tavanai E. The effect of the duration of treatment with antioxidants on age-related hearing loss. Hear Balance Commun 2021; 19:190-196.
129. Tavanai E, Mohammadkhani G, Farahani S, Jalaie S. Protective effects of silymarin against age-related hearing loss in an aging rat model. Indian J Otolaryngol Head Neck Surg 2019; 71:1248-1257.
130. Kawashima T, Harai K, Fujita N, Takahashi R. Ninjinyoeito has a protective effect on the auditory nerve and suppresses the progression of age-related hearing loss in mice. Front Nutr 2020; 7:1-7.
131. Nevado J, Sanz R, Sanchez-Rodriguez C, Garcia-Berrocal JR, Martin-Sanz E, Gonzalez-Garcia JA, et al. Ginkgo biloba extract (EGb761) protects against aging-related caspase-mediated apoptosis in rat cochlea. Acta Otolaryngol 2010; 130:1101-1112.
132. Tian C, Kim YJ, Lim HJ, Kim YS, Park HY, Choung YH. Red ginseng delays age-related hearing and vestibular dysfunction in C57BL/6 mice. Exp Gerontol 2014; 57:224-232.
133. Dong Y, Guo CR, Ding Y, Zhang Y, Song HY, Peng YT, et al. Effects of erlong zuoci decoction on the age-related hearing loss in C57BL/6J mice. J Ethnopharmacol 2016; 181:59-65.
134. Hwang JH, Chan YC, Hsu CJ, Liu TC, Chen JC. Effects of tea drinking on auditory functions in aged subjects. J Nutr Health Aging 2012; 16:252-256.
135. Gopinath B, McMahon CM, Lewis JR, Bondonno NP, Bondonno CP, Burlutsky G, et al. Associations between intake of dietary flavonoids and 10-year incidence of age-related hearing loss. Nutrients 2020; 12:3297-3305.
136. Del Mar Rivas-Chacón L, Yanes-Díaz J, de Lucas B, Riestra-Ayora JI, Madrid-García R, Sanz-Fernández R, et al. Preventive effect of cocoa flavonoids via suppression of oxidative stress-induced apoptosis in auditory senescent cells. Antioxidants (Basel) 2022; 11:1450-1471.
137. Tanigawa T, Shibata R, Kondo K, Katahira N, Kambara T, Inoue Y, et al. Soybean β-conglycinin prevents age-related hearing impairment. PLoS One 2015; 10:1-10.
138. Yang Y-F, Yan X-R, Wu R-X, Li N, Chu M, Dong Y, et al. Network pharmacology and experimental evidence reveal the protective mechanism of Yi-Qi Cong-Ming decoction on age-related hearing loss. Pharm Biol 2022; 60:1478-1490.
139. Lee S, Song J-J, Beyer LA, Swiderski DL, Prieskorn DM, Acar M, et al. Combinatorial Atoh1 and Gfi1 induction enhances hair cell regeneration in the adult cochlea. Sci Rep 2020; 10:21397-14012.
140. Cheng Y-F. Atoh1 regulation in the cochlea: more than just transcription. J Zhejiang Univ Sci B 2019; 20:146-155.
141. Walters BJ, Coak E, Dearman J, Bailey G, Yamashita T, Kuo B, et al. In vivo interplay between p27(Kip1), GATA3, ATOH1, and POU4F3 converts non-sensory cells to hair cells in adult mice. Cell Rep 2017; 19:307-320.
142. Chorath K, Willis M, Morton-Gonzaba N, Moreira A. Mesenchymal stem cells for sensorineural hearing loss: a systematic review of preclinical studies. Mol Biol Rep 2020; 47:4723-4736.
143. Peixoto Pinheiro B, Müller M, Bös M, Guezguez J, Burnet M, Tornincasa M, et al. A potassium channel agonist protects hearing function and promotes outer hair cell survival in a mouse model for age-related hearing loss. Cell Death Dis 2022; 13:595-609.
144. Martinez-Vega R, Partearroyo T, Vallecillo N, Varela-Moreiras G, Pajares MA, Varela-Nieto I. Long-term omega-3 fatty acid supplementation prevents expression changes in cochlear homocysteine metabolism and ameliorates progressive hearing loss in C57BL/6J mice. J Nutr Biochem 2015; 26:1424-1433.
145. Honkura Y, Suzuki J, Sakayori N, Inada H, Kawase T, Katori Y, et al. Effects of enriched endogenous omega-3 fatty acids on age-related hearing loss in mice. BMC Res Notes 2019; 12:768-775.
146. Church MW, Jen KL, Anumba JI, Jackson DA, Adams BR, Hotra JW. Excess omega-3 fatty acid consumption by mothers during pregnancy and lactation caused shorter life span and abnormal ABRs in old adult offspring. Neurotoxicol Teratol 2010; 32:171-181.
147. Tang T-H, Hwang J-H, Yang T-H, Hsu C-J, Wu C-C, Liu T-C. Can nutritional intervention for obesity and comorbidities slow down age-related hearing impairment? Nutrients 2019; 11:1668-1679.
148. Watson N, Ding B, Zhu X, Frisina RD. Chronic inflammation - inflammaging - in the ageing cochlea: a novel target for future presbycusis therapy. Ageing Res Rev 2017; 40:142-148.
149. Iwai H, Inaba M, Van Bui D, Suzuki K, Sakagami T, Yun Y, et al. Treg and IL-1 receptor type 2-expressing CD4+ T cell-deleted CD4+ T cell fraction prevents the progression of age-related hearing loss in a mouse model. J Neuroimmunol 2021; 357:1-8.
150. Lin FR, Chien WW, Li L, Clarrett DM, Niparko JK, Francis HW. Cochlear implantation in older adults. Medicine (Baltimore) 2012; 91:229-241.