A genome-wide association study for age-related hearing impairment in the Saami

This study aimed at contributing to the elucidation of the genetic basis of age-related hearing impairment (ARHI), a common multifactorial disease with an important genetic contribution as demonstrated by heritability studies. We conducted a genome-wide association study (GWAS) in the Finnish Saami, a small, ancient, genetically isolated population without evidence of demographic expansion. The choice of this study population was motivated by its anticipated higher extent of LD, potentially offering a substantial power advantage for association mapping. DNA samples and audiometric measurements were collected from 352 Finnish Saami individuals, aged between 50 and 75 years. To reduce the burden of multiple testing, we applied principal component (PC) analysis to the multivariate audiometric phenotype. The first three PCs captured 80% of the variation in hearing thresholds, while maintaining biologically important audiometric features. All subjects were genotyped with the Affymetrix 100 K chip. To account for multiple levels of relatedness among subjects, as well as for population stratification, association testing was performed using a mixed model. We summarised the top-ranking association signals for the three traits under study. The top-ranked SNP, rs457717 (P-value 3.55 × 10⁻⁷), was associated with PC3 and was localised in an intron of the IQ motif-containing GTPase-activating-like protein (IQGAP2). Intriguingly, the SNP rs161927 (P-value 0.000149), seventh-ranked for PC1, was positioned immediately downstream from the metabotropic glutamate receptor-7 gene (GRM7). As a previous GWAS of a European and Finnish sample set already suggested a role for GRM7 in ARHI, this study provides further evidence for the involvement of this gene.     

Presbycusis: a human temporal bone study of individuals with flat audiometric patterns of hearing loss using a new method to quantify stria vascularis volume

OBJECTIVE: The purpose of this study was to determine the prevalence of stria vascularis atrophy in individuals with presbycusis and flat audiometric patterns of hearing loss. Individuals with presbycusis have historically been categorized by the shape of their audiograms, and flat audiometric thresholds have been reported to be associated with atrophy of the stria vascularis. Stria vascularis volume was not measured in these studies. STUDY DESIGN: Retrospective case review. METHODS: Archival human temporal bones from individuals with presbycusis were selected on the basis of strict audiometric criteria for flat audiometric thresholds. Six temporal bones that met these criteria were identified and compared with 10 temporal bones in individuals with normal hearing. A unique quantitative method was developed to measure the stria vascularis volume in these temporal bones. The hair cell and spiral ganglion cell populations also were quantitatively evaluated. RESULTS: Only one of the six individuals with presbycusis and flat audiometric thresholds had significant atrophy of the stria vascularis. This individual with stria vascularis atrophy also had reduced inner hair cell, outer hair cell, and ganglion cell populations. Three of the individuals with presbycusis had spiral ganglion cell loss, three individuals had inner hair cell loss, and all six individuals had outer hair cell loss. CONCLUSIONS: The results of this investigation suggest that individuals with presbycusis and flat audiometric patterns of hearing loss infrequently have stria vascularis atrophy. Outer hair cell loss alone or in combination with inner hair cell or ganglion cell loss may be the cause of flat audiometric thresholds in individuals with presbycusis.     

The Aging of the Middle Ear in 129S6/SvEvTac and CBA/CaJ Mice: Measurements of Umbo Velocity,Hearing Function,and the Incidence of Pathology

Measurements of umbo velocity and auditory brainstem response (ABR) were made on two different strains of mice, 129S6/SvEvTac (129S6) and CBA/CaJ (CB), within three different age ranges. The velocity measurements were made with a laser Doppler vibrometer using a semiclosed sound delivery system; the frequency range of accurate velocity measurements is from 1 to 21 kHz. The visual detection threshold of the ABR was determined at selected frequencies between 2 and 32 kHz. The velocity results suggest a small but significant change in umbo velocity with age in both strains, between the youngest (1.5–3 months) and mid-aged (12–14 months) groups. There is also a clear difference in the umbo velocity in the youngest animals of the two strains, with the 129S6 having more sensitive middle-ear function than the CB. These results support the existence of a small age-related loss in middle-ear sensitivity in the mouse that was first described in the BALB/6J strain. The age-related changes in middle-ear function observed in both CB and 129S6 are much smaller than the age-related decreases in ABR. Our results also describe a statistically significant increase in the incidence of middle-ear pathology with age in the 129S6.     

听觉器官线粒体DNA缺失在老年聋发病中的意义

目的 探讨听觉器官中线粒体DNA缺失在老年聋发病中的意义。方法:饲养不同年龄组的大鼠,测试ABR阈值,PCR检测其耳蜗、蜗核、大脑、颞肌和外周血中是否存在mtDNA~(4834)缺失,对存在的缺失进行定量分析;PCR产物进行克隆、测序。结果:老年组大鼠的ABR平均阈值为92.22±10.60dBSPL(n=20),中年组为42.75±5.73dBSPL(n=24),青年组为30.50±1.54dBSPL(n:24),老年组大鼠的ABR阈值明显高于中年组和青年组,其差别具有非常显著性的意义(方差分析,P<0.01);(2)所有老年大鼠的听觉器官和颞肌中均存在mtD-NA~(4834)缺失,其缺失发生率高于中年组,青年组mtDNA~(4834)缺失发生率最低;(3)定量分析显示不同年龄大鼠听觉器官中mtDNA~(4834)缺失占总mtDNA的百分比不同,老年组mtDNA~(4834)缺失占总mtDNA的百分比高于中年组。结论:老年大鼠的ABR阈值明显升高,其包括耳蜗、蜗核在内的多种组织中普遍存在的mtDNA~(4834)缺失,提示mtDNA缺失在老化和老年聋的发生中具有重要意义。     

Evidence for independent peripheral and central age-related hearing impairment

Deleterious age-related changes in the central auditory nervous system have been referred to as central age-related hearing impairment (ARHI) or central presbycusis. Central ARHI is often assumed to be the consequence of peripheral ARHI. However, it is possible that certain aspects of central ARHI are independent from peripheral ARHI. A confirmation of this possibility could lead to significant improvements in current rehabilitation practices. The major difficulty in addressing this issue arises from confounding factors, such as other age-related changes in both the cochlea and central non-auditory brain structures. Because gap detection is a common measure of central auditory temporal processing, and gap detection thresholds are less influenced by changes in other brain functions such as learning and memory, we investigated the potential relationship between age-related peripheral hearing loss (i.e., audiograms) and age-related changes in gap detection. Consistent with previous studies, a significant difference was found for gap detection thresholds between young and older adults. However, among older adults, no significant associations were observed between gap detection ability and several other independent variables including the pure tone audiogram average, the Wechsler Adult Intelligence Scale-Vocabulary score, gender, and age. Statistical analyses showed little or no contributions from these independent variables to gap detection thresholds. Thus, our data indicate that age-related decline in central temporal processing is largely independent of peripheral ARHI.     

Identifying hearing impairment and the associated impact on the quality of life among the elderly residing in retirement homes in Pretoria,South Africa

BackgroundAge-Related Hearing Loss (ARHL) is the most widespread sensory disorder in the elderly. Poor audiological support within retirement homes is one of the fundamental issues impacting the Quality of Life (QoL).ObjectivesThe objectives of this study were to: (1) Identify the presence of hearing impairment through a hearing screening test battery in a sample of elderly participants residing in three retirement homes. (2) Determine the psychological, communication-related and social impact of the hearing impairment on the QoL in a sample of elderly participants residing in retirement homes.MethodA prospective cross-sectional research design with quantitative methods of data analysis was used to obtain data from 70 elderly participants (mean age = 79 years, 79% were female). Ten of them used hearing aids. Hearing screening was conducted using otoscopy, tympanometry and air conduction screening (500 Hz–4 kHz). The World Health Organization Quality of Life (WHOQoL) questionnaire was adapted and utilised for the present study.ResultsFindings revealed that 77% of the sample obtained a refer result from the hearing screening protocol indicating a high presence of hearing impairment. Twenty-nine per cent (n = 16) of the participants felt depressed, worried and anxious because of their hearing loss and 20% of participants felt unaccepted by their significant others as a result of their hearing impairment. Hearing difficulties were significantly associated with a reduced QoL (p = 0.045). Eight of the 10 participants who wore hearing aids reported an overall improvement in QoL since receiving and utilising their hearing aids and 20% (n = 2) of hearing aid users reported challenges with maintaining their hearing aids.ConclusionThe findings of this study emphasised the need for an increased role for audiological services provided by audiologists within retirement homes, thereby contributing to an improved QoL.     

Localization of sirtuins (SIRT1-7) in the aged mouse inner ear

Conclusion: The expression of sirtuin in vestibular end organs and cochlea responds differently to age-related changes. Down-regulation of SIRT1, 3, and 5 in the cochlea may weaken the protective activity regarding degeneration of the organ of Corti as well as of spiral ganglion cells, resulting in the development of age-related hearing loss. An increase in SIRT 1, 4, or 5 in vestibular tissue could indicate an increased need of detoxification of reactive oxygen species and an increased anti-ageing potential. Objective: To analyse the expression of sirtuins (SIRT1-7) in the normal young and old mouse inner ears. Methods: Young (8 weeks) and old (22 months) CBA/J mice were used in this study. Localization of SIRT1-7 in the inner ear, i.e. cochlea, vestibular end organs, and vestibular ganglion, was investigated using real-time PCR and immunohistochemistry. Results: In the vestibular end organs, the expression of SIRT1, 2, 4, 5 (both mRNA and protein), SIRT6, and 7 (only mRNA) was found to be increased, while a slightly decreased immunoreactivity was observed in SIRT3. In the cochlea, the expression of SIRT1, 3, and 5 (both mRNA and protein) was decreased in the old mice, whereas no noticeable difference was observed regarding SIRT2, 4, 6, or 7.     

Different Cellular and Genetic Basis of Noise-Related Endocochlear Potential Reduction in CBA/J and BALB/cJ Mice

The acute and permanent effects of noise exposure on the endocochlear potential (EP) and cochlear lateral wall were evaluated in BALB/cJ (BALB) inbred mice, and compared with CBA/J (CBA) and C57BL/6 (B6) mice. Two-hour exposure to broadband noise (4–45 kHz) at 110 dB SPL leads to a ~50 mV reduction in the EP in BALB and CBA, but not B6. EP reduction in BALB and CBA is reliably associated with characteristic acute cellular pathology in stria vascularis and spiral ligament. By 8 weeks after exposure, the EP in CBA mice has returned to normal. In BALBs, however, the EP remains depressed by an average ~10 mV, so that permanent EP reduction contributes to permanent threshold shifts in these mice. We recently showed that the CBA noise phenotype in part reflects the influence of a large effect quantitative trait locus on Chr. 18, termed Nirep (Ohlemiller et al., Hear Res 260:47–53, 2010b). While CBA “EP susceptibility” alleles are dominant to those in B6, examination of (B6 × BALB) F1 hybrid mice and (F1 × BALB) N2 backcross mice revealed that noise-related EP reduction and associated cell pathology in BALBs are inherited in an autosomal recessive manner, and are dependent on multiple genes. Moreover, while N2 mice formed from B6 and CBA retain strong correspondence between acute EP reduction, ligament pathology, and strial pathology, N2s formed from B6 and BALB include subsets that dissociate pathology of ligament and stria. We conclude that the genes and cascades that govern the very similar EP susceptibility phenotypes in BALB and CBA mice need not be the same. BALBs appear to carry alleles that promote more pronounced long term effects of noise on the lateral wall. Separate loci in BALBs may preferentially impact stria versus ligament.     

老年性耳聋患者内皮祖细胞功能变化

目的探讨老年性耳聋患者外周血内皮祖细胞(EPCs)功能的变化。方法分离老年性耳聋患者(观察组)和健康老年人(对照组)外周血中单个核细胞,诱导其分化为EPCs,检测2组培养第7天的EPCs集落数目和细胞计数、黏附、增殖和迁移能力并进行比较。结果观察组EPCs集落数目(1.40±0.37)个少于对照组(2.88±0.48)个,差别有统计学意义(t=7.734,P<0.01)。观察组EPCs细胞计数(54.32±9.24)个少于对照组(67.64±8.39)个,差别有统计学意义(t=3.376,P<0.01)。与对照组相比,观察组黏附细胞数明显减少(P<0.05);EPCs增殖能力和迁移能力下降,差别均有统计学意义(P<0.01)。结论 EPCs功能下降可能为老年性耳聋的发病机制之一。