Presbycusis Hearing Loss Research Articles

Prognostic Gene Expression Signature for Age-Related Hearing Loss.

BackgroundOur study aimed to determine the pathological mechanism of presbycusis at the molecular level, and determine potential biomarkers for the same.MethodsDifferentially expressed genes (DEGs) for presbycusis were obtained by analyzing the microarray data sets (GSE6045 and GSE49543) downloaded from the Gene Expression Omnibus (GEO). Gene ontology (GO), Kyoto Encyclopedia of Genes and Genome (KEGG) pathway, and protein-protein interaction (PPI) network analyses, and Gene Set Enrichment Analysis (GSEA) were performed to analyze the biological functions, molecular pathways, autophagy-related molecular markers, and the immune microenvironment of the DEGs in presbycusis. Then the prognostic roles of the hub genes were analyzed and verified in vivo.ResultsIn the old mild hearing loss group (27.7 ± 3.4 months old), 27 down-regulated and 99 up-regulated genes were significantly differentially expressed compared with those in the young control group (3.5 ± 0.4 months old). In the old severe hearing loss group (30.6 ± 1.9 months old), 131 down-regulated and 89 up-regulated genes were significantly differentially expressed compared with those in the young control group. The results of the GO, GSEA, KEGG pathway, and immune infiltration analyses showed that the enrichment terms were mainly focused on immune response in mild presbycusis, and immune response and cell death in severe presbycusis. In the PPI network, autophagy-related genes ATG5, ATG7 showed the highest node scores in mild presbycusis; whereas MTOR, BECN1 showed the highest scores in severe presbycusis. In the GSE49543 data set, four genes (Ywhag, Mapre2, Fgf1, Acss2) were used to construct the prognostic model, and those four genes were significantly up-regulated in the rat model of presbycusis.ConclusionOur study is the first to report the difference in autophagy factors and immune microenvironment among different degrees of hearing loss in presbycusis. Furthermore, we provide the prognostic gene expression signature for age-related hearing loss, intending to develop preventative therapies.

Cingulate Cortex Atrophy Is Associated With Hearing Loss in Presbycusis With Cochlear Amplifier Dysfunction.

Age-related hearing loss is associated with cognitive decline and has been proposed as a risk factor for dementia. However, the mechanisms that relate hearing loss to cognitive decline remain elusive. Here, we propose that the impairment of the cochlear amplifier mechanism is associated with structural brain changes and cognitive impairment. Ninety-six subjects aged over 65 years old (63 female and 33 male) were evaluated using brain magnetic resonance imaging, neuropsychological and audiological assessments, including distortion product otoacoustic emissions as a measure of the cochlear amplifier function. All the analyses were adjusted by age, gender and education. The group with cochlear amplifier dysfunction showed greater brain atrophy in the cingulate cortex and in the parahippocampus. In addition, the atrophy of the cingulate cortex was associated with cognitive impairment in episodic and working memories and in language and visuoconstructive abilities. We conclude that the neural abnormalities observed in presbycusis subjects with cochlear amplifier dysfunction extend beyond core auditory network and are associated with cognitive decline in multiple domains. These results suggest that a cochlear amplifier dysfunction in presbycusis is an important mechanism relating hearing impairments to brain atrophy in the extended network of effortful hearing.

Association between the mitochondrial DNA4977 common deletion in the hair shaft and hearing loss in presbycusis.

The aim of the present study was to examine the role of the mitochondrial (mt) DNA common deletion (CD) 4977 (mtDNACD4977) in the hair shaft in patients with presbycusis. A total of 87 individuals with presbycusis and 95 normal‑hearing controls were selected based on strict audiometric criteria. Nested polymerase chain reaction (PCR), sequencing and quantitative (q)PCR were used to examine the expression levels of mtDNACD4977 in the hair shaft in presbycusis. Nested PCR of the hair shaft demonstrated that 8/95 cases with normal hearing were found to be positive for mtDNACD4977, as compared with 59/87 cases in the presbycusis group. The mtDNACD4977 was positive in 22/43 cases with mild‑to‑moderate hearing loss, 25/31 cases with moderate‑to‑severe, severe hearing loss, and 12/13 cases with profound deafness. Statistically significant differences in mtDNACD4977 expression were identified among all of the groups (P<0.001). The sequencing and qPCR assays demonstrated a trend towards an increase in the mean CD level of mtDNACD4977 with a more severe hearing loss at 8 kHz (r=0.778, P<0.001) and all ranges of frequency (r=0.858, P<0.001). In conclusion, the present study demonstrates a correlation between mtDNACD4977 in the human hair shaft and the severity of hearing loss in presbycusis.

Presbycusis phenotypes form a heterogeneous continuum when ordered by degree and configuration of hearing loss

Many reports have documented age-by-frequency increases in average auditory thresholds in various human populations. Despite this, the prevalence of different patterns of hearing loss in presbycusis remains uncertain. We examined ‘presbycusis phenotypes’ in a database of 960 subjects (552 female, 408 male, 18–92 years) that each had 30 measures of peripheral hearing sensitivity: pure tone audiograms for left and right ears from 0.25 to 8 kHz and DPOAE for each ear with F mean = 1–6.4 kHz. Surprisingly, the hearing phenotypes did not naturally separate into discrete classes of presbycusis. Principal component (PC) analysis revealed that two principal components account for 74% of the variance among the 30 measures of hearing. The two components represent the overall degree (PC1) and configuration of loss (Flat vs. Sloping; PC2) and the phenotypes form a continuum when plotted against them. A heuristic partitioning of this continuum produced classes of presbycusis that vary in their degree of Sloping or Flat hearing loss, suggesting that the previously reported sub-types of presbycusis arise from the categorical segregation of a continuous and heterogeneous distribution. Further, most phenotypes lie intermediate to the extremes of either Flat or Sloping loss, indicating that if audiometric configuration does predict presbycusis etiology, then a mixed origin is the most prevalent.