title: NAD(+) Metabolism in Age-Related Hearing Loss.
abstract: Age-related hearing loss (ARHL), a degenerative disorder characterized by age-dependent progressive increase in the threshold of auditory sensitivity, affects 40% of people over the age of 65, and it has emerged as an important social and public health problem. Various factors, including genetic and environmental components, are known to affect both the onset and severity of ARHL. In particular, age-dependent changes in cellular oxidative stress and inflammatory responses accompanied by altered cellular signaling and gene expression progressively affect the function of the auditory system and eventually lead to hearing impairment. Recent findings suggest that a disturbance of intracellular NAD(+) levels is clinically related to the progression of age-associated disorders. Therefore, maintenance of optimal intracellular NAD(+) levels may be a critical factor for cellular senescence, and thus, understanding its molecular signaling pathways would provide critical insights into the prevention and treatment of ARHL as well as other age-related diseases. In this review, we describe the role of NAD(+) metabolism in aging and age-related diseases, including ARHL, and discuss a potential strategy for prevention or treatment of ARHL with a particular interest in NAD(+)-dependent cellular pathways.
authors.affiliation: Center for Metabolic Function Regulation & Department of Microbiology, Wonkwang University School of Medicine, 460 Iksan-Daero, Iksan, Jeonbuk, 570-749, Korea.
authors.forename: Hyung-Jin
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Center for Metabolic Function Regulation & Department of Microbiology, Wonkwang University School of Medicine, 460 Iksan-Daero, Iksan, Jeonbuk, 570-749, Korea.
authors.forename: Gi-Su
authors.initials: GS
authors.lastname: Oh
authors.affiliation: Center for Metabolic Function Regulation & Department of Microbiology, Wonkwang University School of Medicine, 460 Iksan-Daero, Iksan, Jeonbuk, 570-749, Korea.
authors.forename: Seong-Kyu
authors.initials: SK
authors.lastname: Choe
authors.affiliation: Life Science Research Center, KT&G LIFE SCIENCES, Suwon, 443-813, Korea.
authors.forename: Tae Hwan
authors.initials: TH
authors.lastname: Kwak
authors.affiliation: Center for Metabolic Function Regulation & Department of Microbiology, Wonkwang University School of Medicine, 460 Iksan-Daero, Iksan, Jeonbuk, 570-749, Korea.
authors.forename: Raekil
authors.initials: R
authors.lastname: Park
authors.affiliation: Center for Metabolic Function Regulation & Department of Microbiology, Wonkwang University School of Medicine, 460 Iksan-Daero, Iksan, Jeonbuk, 570-749, Korea.
authors.forename: Hong-Seob
authors.initials: HS
authors.lastname: So
keywords: Age-related hearing loss; NAD+; degenerative disorder; metabolism
references.citation: J Assoc Res Otolaryngol. 2007 Sep;8(3):338-55
references.pmid: 17516123
references.citation: Cell Metab. 2008 Aug;8(2):157-68
references.pmid: 18599363
references.citation: Cell. 2008 May 16;133(4):612-26
references.pmid: 18485870
references.citation: Cell. 2007 May 4;129(3):473-84
references.pmid: 17482543
references.citation: J Gerontol. 1956 Jul;11(3):298-300
references.pmid: 13332224
references.citation: PLoS One. 2012;7(10):e47122
references.pmid: 23071729
references.citation: Circ Res. 2009 Apr 10;104(7):842-50
references.pmid: 19229058
references.citation: J Biol Chem. 2005 Jun 3;280(22):21313-20
references.pmid: 15795229
references.citation: Sci Rep. 2011;1:70
references.pmid: 22355589
references.citation: Clin Geriatr Med. 2009 Nov;25(4):715-32, ix
references.pmid: 19944269
references.citation: Audiol Neurootol. 2004 Jan-Feb;9(1):23-33
references.pmid: 14676471
references.citation: Proc Natl Acad Sci U S A. 2008 Feb 19;105(7):2325-30
references.pmid: 18287083
references.citation: J Biol Chem. 2001 Jun 22;276(25):22559-64
references.pmid: 11309386
references.citation: Antioxid Redox Signal. 2007 Jul;9(7):931-42
references.pmid: 17508915
references.citation: N Engl J Med. 1997 Oct 2;337(14):986-94
references.pmid: 9309105
references.citation: Nat Rev Cancer. 2009 Oct;9(10):749-58
references.pmid: 19776744
references.citation: Curr Pharm Des. 2010;16(22):2493-503
references.pmid: 20500145
references.citation: EMBO J. 2004 Jun 16;23(12):2369-80
references.pmid: 15152190
references.citation: Crit Rev Biochem Mol Biol. 2013 Jul-Aug;48(4):397-408
references.pmid: 23742622
references.citation: PLoS One. 2010 May 05;5(5):e10486
references.pmid: 20463968
references.citation: Kidney Int. 2014 Mar;85(3):547-60
references.pmid: 24025646
references.citation: Ageing Res Rev. 2011 Jul;10(3):319-29
references.pmid: 21145432
references.citation: J Neurosci. 2006 Sep 20;26(38):9794-804
references.pmid: 16988050
references.citation: Exp Gerontol. 2011 Jun;46(6):413-25
references.pmid: 21211561
references.citation: Nature. 2002 Jul 18;418(6895):344-8
references.pmid: 12124627
references.citation: Bone Marrow Transplant. 2001 Aug;28(4):323-8
references.pmid: 11571502
references.citation: Acad Emerg Med. 2004 Feb;11(2):125-30
references.pmid: 14759952
references.citation: Am J Physiol Regul Integr Comp Physiol. 2007 Jan;292(1):R18-36
references.pmid: 16917020
references.citation: Cell. 2001 Oct 19;107(2):149-59
references.pmid: 11672523
references.citation: Mol Biol Cell. 2005 Oct;16(10):4623-35
references.pmid: 16079181
references.citation: Nature. 2000 Feb 17;403(6771):795-800
references.pmid: 10693811
references.citation: J Neurosci Res. 2006 Mar;83(4):575-83
references.pmid: 16429448
references.citation: Genes Dev. 2004 Jan 1;18(1):12-6
references.pmid: 14724176
references.citation: J Pathol. 2007 Jan;211(2):188-97
references.pmid: 17200945
references.citation: J Neurosci Res. 2005 Jan 1-15;79(1-2):216-23
references.pmid: 15562437
references.citation: Audiology. 1988;27(6):305-12
references.pmid: 3240128
references.citation: Exp Gerontol. 1980;15(6):575-91
references.pmid: 7009178
references.citation: Cold Spring Harb Symp Quant Biol. 2000;65:297-302
references.pmid: 12760043
references.citation: Cell. 2010 Nov 24;143(5):802-12
references.pmid: 21094524
references.citation: Mol Cell. 2003 Feb;11(2):437-44
references.pmid: 12620231
references.citation: Chem Biol Interact. 2000 Dec 1;129(1-2):77-97
references.pmid: 11154736
references.citation: Diabet Med. 2009 May;26(5):483-8
references.pmid: 19646187
references.citation: Nature. 2006 Nov 16;444(7117):337-42
references.pmid: 17086191
references.citation: Exp Gerontol. 2000 May;35(3):299-305
references.pmid: 10832051
references.citation: Aging Trends. 2001 Mar;(2):1-8
references.pmid: 11894223
references.citation: Trends Endocrinol Metab. 2009 Sep;20(7):325-31
references.pmid: 19713122
references.citation: Trends Biochem Sci. 2004 Mar;29(3):111-8
references.pmid: 15003268
references.citation: Cell Metab. 2010 Dec 1;12(6):662-7
references.pmid: 21109198
references.citation: J Biol Chem. 2005 Apr 8;280(14):13560-7
references.pmid: 15653680
references.citation: Neurobiol Aging. 2007 Oct;28(10):1613-22
references.pmid: 16890326
references.citation: PLoS One. 2011 Apr 26;6(4):e19194
references.pmid: 21541336
references.citation: Biochem J. 2009 Jan 1;417(1):1-13
references.pmid: 19061483
references.citation: FASEB J. 2007 Sep;21(11):2642-54
references.pmid: 17431096
references.citation: Biochem Biophys Res Commun. 2013 Jun 14;435(4):727-32
references.pmid: 23692925
references.citation: Proc Natl Acad Sci U S A. 2000 Dec 19;97(26):14178-82
references.pmid: 11106374
references.citation: Proc Natl Acad Sci U S A. 2002 Oct 15;99(21):13653-8
references.pmid: 12374852
references.citation: J Assoc Res Otolaryngol. 2001 Jun;2(2):118-29
references.pmid: 11550522
references.citation: Cell Metab. 2012 Jun 6;15(6):838-47
references.pmid: 22682224
references.citation: Audiol Neurootol. 2007;12(6):345-58
references.pmid: 17664866
references.citation: Exp Gerontol. 2012 Feb;47(2):198-201
references.pmid: 22143179
references.citation: Protein Cell. 2011 Jun;2(6):456-62
references.pmid: 21748595
references.citation: Diabetes. 2009 Apr;58(4):965-74
references.pmid: 19136651
references.citation: Ann Med. 2007;39(5):335-45
references.pmid: 17701476
references.citation: Arch Otolaryngol Head Neck Surg. 1993 Feb;119(2):156-61
references.pmid: 8427676
references.citation: Neurochem Int. 2013 Apr;62(5):757-63
references.pmid: 23357482
references.citation: Eur J Biochem. 1979 Nov 1;101(1):135-42
references.pmid: 228934
references.citation: Genes Dev. 2008 Apr 1;22(7):931-44
references.pmid: 18381895
references.citation: Aging Dis. 2012 Feb;3(1):130-40
references.pmid: 22500274
references.citation: Science. 2005 Jul 15;309(5733):481-4
references.pmid: 16020738
references.citation: Nature. 2007 May 31;447(7144):545-9
references.pmid: 17538612
references.citation: Biochim Biophys Acta. 1978 Nov 1;543(4):576-82
references.pmid: 214144
references.citation: Antioxid Redox Signal. 2008 Feb;10(2):179-206
references.pmid: 18020963
references.citation: Genes Dev. 2008 Jul 1;22(13):1753-7
references.pmid: 18550784
references.citation: Neuroreport. 2002 Feb 11;13(2):213-6
references.pmid: 11893912
references.citation: J Acoust Soc Am. 1997 Jun;101(6):3546-53
references.pmid: 9193043
references.citation: Neurosci Lett. 1999 Jan 4;259(1):21-4
references.pmid: 10027546
references.citation: Cardiovasc Res. 2011 Aug 1;91(3):519-27
references.pmid: 21502369
references.citation: Science. 1996 Jul 5;273(5271):59-63
references.pmid: 8658196
references.citation: J Cell Biol. 2002 Aug 19;158(4):647-57
references.pmid: 12186850
references.citation: Gerontology. 1999 Nov-Dec;45(6):323-8
references.pmid: 10559650
references.citation: Proc Natl Acad Sci U S A. 1994 Nov 8;91(23):10771-8
references.pmid: 7971961
references.citation: Mol Cell Biol. 2009 Aug;29(15):4116-29
references.pmid: 19470756
references.citation: Mol Cell. 2010 Jul 9;39(1):8-24
references.pmid: 20603072
references.citation: Cell. 2006 Sep 8;126(5):941-54
references.pmid: 16959573
references.citation: Biochem Biophys Res Commun. 2003 Sep 5;308(4):809-13
references.pmid: 12927790
references.citation: Science. 2005 Oct 14;310(5746):314-7
references.pmid: 16224023
references.citation: Biochim Biophys Acta. 2009 May;1787(5):414-20
references.pmid: 19007744
references.citation: Cell. 2009 May 15;137(4):609-22
references.pmid: 19450511
references.citation: Audiology. 1986;25(6):329-37
references.pmid: 3593092
references.citation: J Pharmacol Exp Ther. 2008 Mar;324(3):883-93
references.pmid: 18165311
references.citation: Cell Metab. 2011 Apr 6;13(4):461-468
references.pmid: 21459330
references.citation: PLoS One. 2012;7(7):e42357
references.pmid: 22848760
references.citation: Mol Cell Biol. 2009 Mar;29(5):1363-74
references.pmid: 19103747