Role of mitochondrial dysfunction and mitochondrial DNA mutations in age-related hearing loss

Yamasoba, Tatsuya; Someya, Shinichi; Yamada, Chikashi; Weindruch, Richard; Prolla, Tomas A.; Tanokura, Masaru

doi:10.1016/j.heares.2006.06.004

Cited by 118 publications

(91 citation statements)

References 48 publications

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“…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.…”

mentioning

confidence: 99%

“…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). Because of its high prevalence, AHL is a major social and health problem.…”

mentioning

confidence: 99%

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

Someya

Kondo

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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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

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mentioning

confidence: 99%

mentioning

confidence: 99%

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

Someya

Kondo

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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287

304

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“…The ABR analysis was used to monitor the progression of AHL. Both control and CR mice from the Study 1 group displayed large and similar ABR threshold elevations at all frequencies measured (4,8,16,32, and 64 kHz); these results indicate that CR until midlife (from 2 to 10 months of age) can not prevent AHL in this strain. This may be due to the fact that CR was stopped too early in the life of the CBA mice to be beneficial.…”

Section: Studies In Micementioning

confidence: 74%

“…Willott and co-workers employed the same diet regimens to study DBA, WB, and BALB strains [20]. Again, CR failed to delay the onset of AHL in these 3 strains when tested at 23 months of age; no ABR thresholds were obtained even with 100 dB SPL at 4, 8, 16, 24, and 32 kHz frequencies in both the control and CR mice of the DBA strain group, while both the control and CR mice of the WB and BALB strain groups displayed large ABR threshold elevations at all frequencies measured (4,8,16,32, and 64 kHz). This may be due to the fact that the time points of the hearing tests in these strains were too late for CR to be beneficial since all strains develop severe to complete hearing loss by 3-23 months of age.…”

Section: Studies In Micementioning

confidence: 82%

“…In Japan, people over 65 years of age numbered 25.6 million in 2007 (20.0% of the population) (Statistic Bureau, Ministry of Internal Affairs and Communications of Japan: http://www.stat.go.jp/english/data/jinsui/2.htm) and this elderly population is expected to grow to be 35.9 million (39.0% of the population) in 2050 (National Institute of Population and Social Security Research: http://www.ipss.go.jp/indexe.html). AHL affects nearly half the population between 48 and 92 years of age in Wisconsin [2], and 23% of people between 65 and 75 years of age and 40% of people over 75 years of age in the US [3,4]. Because of the high prevalence of AHL and because the overall number of people with it is rapidly growing as lifespan increases in industrialized nations, AHL is a major social and health problem.…”

Section: Introductionmentioning

confidence: 99%

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Effects of Caloric Restriction on Age-Related Hearing Loss in Rodents and Rhesus Monkeys

Someya¹,

Tanokura²,

Weindruch³

et al. 2010

CAS

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Age-related hearing loss (AHL), also known as presbycusis, is a universal feature of mammalian aging and is the most frequently occurring sensory disorder in the elderly population. AHL is characterized by a decline of auditory function and loss of hair cells and spiral ganglion neurons in the cochlea of the inner ear. It has been postulated that AHL occurs gradually as a result of the cumulative effect with aging of exposure to noise, diet, oxidative damage, and mitochondrial DNA mutations. However, the molecular mechanisms of AHL remain unclear and no preventative or therapeutic interventions have been developed. A growing body of evidence suggests increased oxidative damage with aging to macromolecules such as DNA, proteins, and lipids may play a causal role in aging and age-related diseases. Caloric restriction (CR) extends the lifespan of most mammalian species, delays the onset of multiple age-related diseases, and attenuates both the degree of oxidative damage and the associated decline in physiological function. Here, we review studies on CR's ability to prevent cochlear pathology and AHL in laboratory animals and discuss potential molecular mechanisms of CR's actions.

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Germanium, Tin, and Copper

King,

Avery

2023

Patty's Toxicology

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A German chemist Clemens A. Winkler first isolated Germanium in 1886 from the mineral argyrodite. Germanium (Ge) is a semiconducting metal from Group IVA of the periodic table, and it forms a series of hydrides. Interest in the organogermanium compounds has centered on their antimicrobial activity and the fact that their mammalian toxicity is lower than the corresponding derivatives of tin or lead. Today, germanium is used in the computer industry (as resistors on computer chips), in fiber optics, solar applications, and metallurgy, and has also been used in supplements and for chemotherapy agents. The inorganic compound, Ge tetrachloride, has been shown to cause skin and eye irritation, and inhalation of high exposure concentrations can cause necrosis of the tracheal mucosa, bronchitis, and interstitial pneumonitis. In recent years, germanium nanoparticles (NPs) have received increased attention as a favorable alternative to II–VI and IV–VI semiconductor materials. It was found that GE nano length imogolites persisted in the lungs of tested animals and promoted genotoxicity, sustained inflammation, and fibrosis. The Bronze Age began approximately 3500 BCE with the discovery that alloying tin (Sn) with easily smelted soft copper made it harder and stronger. Tin and copper are important for the manufacture of numerous commercially valuable products including electrical conductors, piping, and antimicrobial agents. Tin is a solid, unreactive metal in Group IVA of the periodic table and has the largest number of stable isotopes of any element. Tin also has many unstable isotopes with half‐lives ranging from 2.2 min to 105 years. The physical and chemical properties of tin and some of its compounds are provided. Organotins, such as tributyltin (TBT) and trimethyltin (TMT) compounds, have drawn much attention because of their toxicity and wide range of adverse effects in experimental animals and in humans. Laboratory research has demonstrated that tributyltin is an endocrine disruptor in mammals, affects the immune system, is reported to be teratogenic, and is a reproductive and developmental toxicant. Occupational exposure to trimethyltin has been shown to increase the risk of kidney stones among TMT‐exposed workers. Copper (Cu) is in Group IB of the periodic table. The electrical conductivity and malleability of copper are important commercial properties of the metal. Exposure to copper can occur from environmental sources such as food, water from copper pipes, and soil ingestion near copper smelting operations. The adverse health effects associated with copper production may be due to the sulfur oxides generated during smelting or because of the impurities, such as arsenic and antimony. Results from numerous experimental studies support the position that reactive oxygen species (ROS)‐generated oxidative damage plays an important role in Cu toxicity. Copper processing workers were found to have had significantly lower pulmonary function parameter test results, significantly increased serum levels of malondialdehyde, and their total antioxidative capacity and glutathione concentrations were significantly lower than controls. Also, based on the comet assay, it was found that significant DNA damage occurred in leukocytes among the copper processing workers. Copper nanoparticles are being used in a wide range of applications. Experimental studies in animals have reported that inhalation of Cu NPs was shown to cause the increased deposition of copper in the lung and liver and an undesired modulation of immune system response. Inhalation of Cu NPs in rats resulted in dose‐dependent lung inflammation and cytotoxicity, and histopathology examinations of the lungs revealed alveolitis, bronchitis, and vacuolation of the respiratory epithelium and emphysema. In a study of the hemolytic effects of copper oxide (CuO) nanoparticles and bulk CuO in human red blood cells, it was demonstrated that CuO NPs caused toxic hemolytic effects in a concentration‐dependent manner and that the CuO NPs effectively destroy human red blood cells in comparison to bulk CuO.

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Role of mitochondrial dysfunction and mitochondrial DNA mutations in age-related hearing loss

Cited by 118 publications

References 48 publications

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

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

Effects of Caloric Restriction on Age-Related Hearing Loss in Rodents and Rhesus Monkeys

Germanium, Tin, and Copper

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