Cellular Mechanisms of Age-Related Hearing Loss

An Oral Combination of Vitamins A, C, E, and Mg++ Improves Auditory Thresholds in Age-Related Hearing Loss

“…Despite of its high prevalence and the wealth of studies available, the complex etiopathogenesis of this chronic, continuous and irreversible condition, is still not well understood ( Huang and Tang, 2010 ; Fetoni et al, 2011 ; Yamasoba et al, 2013 ; Tavanai and Mohammadkhani, 2017 ). Based on evaluations of the temporal bones and audiometric tests of aged patients, six histopathological types of presbycusis have been described: (1) sensory, which occurs with loss of outer hair cells and supporting cells; (2) neural, which is associated with loss of spiral ganglion neurons; (3) strial or metabolic, related to degeneration or atrophy of the stria vascularis; (4) cochlear conductive or mechanical, which is associated with changes in the stiffness of the basilar membrane; (5) mixed presbycusis, characterized by the coexistence of more than one of those forms of presbycusis; and (6) indeterminate presbycusis, represented by the cases (one in four people) that do not fit into any of the types above mentioned and therefore, its pathophysiological mechanism is unknown ( Schuknecht et al, 1974 ; Schuknecht and Gacek, 1993 ; Bielefeld et al, 2010 ; Huang and Tang, 2010 ; Schmiedt, 2010 ; Lee, 2013 ; Yamasoba et al, 2013 ; Melgar-Rojas et al, 2015b ). This clear-cut classification has been challenged ( Ohlemiller and Frisina, 2008 ; Melgar-Rojas et al, 2015b ) as it is likely that in most instances clinical presbycusis comprises an accumulation of cochlear pathologies ( Engle et al, 2013 ).…”

“…However, it is still valid as a framework to add new knowledge on ARHL mechanisms. In fact, several interrelated factors have been postulated to explain the pathophysiology of this sensory dysfunction ( Bielefeld et al, 2010 ; Huang and Tang, 2010 ; Schmiedt, 2010 ; Fetoni et al, 2011 ; Yamasoba et al, 2013 ; Melgar-Rojas et al, 2015b ). Oxidative stress and degenerative structural and functional alterations in the stria vascularis, likely in combination in most instances, seem to have a relevant role in the genesis of ARHL.…”

“…As far as oxidative stress is concerned, ARHL reflects incapacity of the endogenous antioxidant systems to eliminate excess free radicals. This, in turn, would induce oxidative damage and loss of hair cells, supporting cells, ganglion cells, and fibrocytes in the stria vascularis ( Bielefeld et al, 2010 ; Huang and Tang, 2010 ; Fetoni et al, 2011 ; Yamasoba et al, 2013 ; Fujimoto and Yamasoba, 2014 ; Alvarado et al, 2015b ; Melgar-Rojas et al, 2015b ). Excess free radical formation seems to be part of a common pathogenic pathway ( Alvarado et al, 2015b ; Tavanai and Mohammadkhani, 2017 ) which is involved in other forms of hearing loss such as NIHL and DIHL ( Henderson et al, 2006 ; Le Prell et al, 2007a , b ; Bielefeld et al, 2010 ; Fetoni et al, 2011 ) as weel as in many neurodegenerative pathologies ( Ames et al, 1993 ; Lin and Beal, 2006 ; Gardiner et al, 2009 ) that present high incidence of hearing loss ( Lin Y.S.…”

“…To date there are no effective medications to cure or prevent ARHL. This is partly due to the fact that the etiopathogenesis of this sensory dysfunction is multifactorial and highly complex and still remains unclear ( Huang and Tang, 2010 ; Fetoni et al, 2011 ; Yamasoba et al, 2013 ; Melgar-Rojas et al, 2015b ), which limits therapeutic approaches.…”

“…Among mechanisms underlying ARHL ( Chisolm et al, 2003 ; Mills and Schmiedt, 2004 ; Fetoni et al, 2011 ), one major contributor is oxidative stress ( Fetoni et al, 2011 ; Fujimoto and Yamasoba, 2014 ; Alvarado et al, 2015b ), i.e., an imbalance between removal and production of highly oxidative free radicals, by-products of oxidative metabolism. Accumulation of damage to the nuclear and mitochondrial genome and altered protein regulation and homeostasis, both at the core of the systemic aging process ( López-Otín et al, 2013 ; Melgar-Rojas et al, 2015b ), may lead to mitochondrial failure and breakdown of antioxidant enzymatic system with associated free radical build-up in the aging auditory receptor ( Fetoni et al, 2011 ; Fujimoto and Yamasoba, 2014 ; Alvarado et al, 2015b ). During aging, oxidative stress may easily target auditory hair cells, cells in the stria vascularis or spiral ganglion neurons because they are heavily dependent on oxidative metabolism, due to the unusually high metabolic demands of mechanoelectrical transduction.…”