Age-related hearing loss in C57BL/6J mice is mediated by Bak-dependent mitochondrial apoptosis

Abstract

Age-related hearing loss (AHL), known as presbycusis, is a universal feature of mammalian aging and is the most common sensory disorder in the elderly population. The molecular mechanisms underlying AHL are unknown, and currently there is no treatment for the disorder. Here we report that C57BL/6J mice with a deletion of the mitochondrial pro-apoptotic gene Bak exhibit reduced age-related apoptotic cell death of spiral ganglion neurons and hair cells in the cochlea, and prevention of AHL. Oxidative stress induces Bak expression in primary cochlear cells, and Bak deficiency prevents apoptotic cell death. Furthermore, a mitochondrially targeted catalase transgene suppresses Bak expression in the cochlea, reduces cochlear cell death, and prevents AHL. Oral supplementation with the mitochondrial antioxidants ␣-lipoic acid and coenzyme Q 10 also suppresses Bak expression in the cochlea, reduces cochlear cell death, and prevents AHL. Thus, induction of a Bak-dependent mitochondrial apoptosis program in response to oxidative stress is a key mechanism of AHL in C57BL/6J mice.aging ͉ antioxidant ͉ cochlea ͉ oxidative stress ͉ presbycusis A ge-related hearing loss (AHL), also known as presbycusis, is characterized by an age-dependent decline of auditory function associated with loss of sensory hair cells, spiral ganglion (SG) neurons, and stria vascularis cells in the cochlea of the inner ear (1, 2). Hair cells and SG neurons do not regenerate in mammals, and loss of these long-lived cochlear cells leads to permanent hearing impairment. AHL affects more than 40% of people greater than 65 years of age in the United States (1, 2) and is projected to afflict more than 28 million Americans by 2030 (1, 3

Ubiquinol-10 Supplementation Activates Mitochondria Functions to Decelerate Senescence in Senescence-Accelerated Mice

“…These findings may support the possibility that ubiquinol-10 has anti-aging effects, because ubiquinone-10 is readily reduced to ubiquinol-10 after dietary uptake (33,63) and a ratio of ubiquinol-10 to total CoQ10 of more than 85% is maintained in the plasma (40,70). Dietary supplementation with ubiquinol-10 produces beneficial effects for several agerelated diseases, such as cardiovascular disease, diabetes, agerelated hearing loss (AHL), and Parkinson's disease (50,61,62,68). Our recent study identified many ubiquinol-10-sensitive genes that are regulated by peroxisome proliferatoractivated receptor-alpha (PPARa) in the liver (54).…”

“…3 and 4). Previous studies showed that the mean ABR hearing threshold at low frequencies was significantly lower in ubiquinone-10-supplemented control mice (61,62). Similar to SAMP1 mice, ubiquinone-10 suppressed AHL in C57BL/6J mice by increasing antioxidant activities via SIRT3 activation.…”

Mitochondrial Sirtuins and Their Relationships with Metabolic Disease and Cancer

“…Studies have shown that CR delays the onset of AHL and reduces cochlear pathology (141,150) by reducing oxidative stress (150), which plays a major role in AHL (73,149). Notably, SIRT3 is required for the beneficial effect of CR in preserving auditory function.…”

Vestibuler rehabilitation in bilateral vestibulopaty

“…Şimdiki çalışmalar VOR in oluşturulması için uygun elektik stimulasuyon modelini bulmak ve VOR' deki adaptif mekanizmaları geliştirmek üzerine odaklanmıştır (56). Kulakta bulunan saç hücrelerinin yenilenmesini teşvik etmek için geliştirilen vestibuler protezler, genetik olarak gentamisin duyarlılığnın tespiti, kulaktaki saçlı hücre kaybı için alfa lipoik asit coenzyme Q10 gibi anti oksidan kullanımı gündemde olan tedavilerdir (57,58).…”