The incidences of presbycusis and dementia are high among geriatric diseases. Presbycusis is the general term applied to age-related hearing loss and can be caused by many risk factors, such as noise exposure, smoking, medication, hypertension, family history, and other factors. Mutation of mitochondrial DNA in hair cells, spiral ganglion cells, and stria vascularis cells of the cochlea is the basic mechanism of presbycusis. Dementia is a clinical syndrome that includes the decline of cognitive and conscious states and is caused by many neurodegenerative diseases, of which Alzheimer’s disease (AD) is the most common. The amyloid cascade hypothesis and tau hypothesis are the two major hypotheses that describe the AD pathogenic mechanism. Recent studies have shown that deposition of Aβ and hyperphosphorylation of the tau protein may cause mitochondrial dysfunction. An increasing number of papers have reported that, on one hand, the auditory system function in AD patients is damaged as their cognitive ability declines and that, on the other hand, hearing loss may be a risk factor for dementia and AD. However, the relationship between presbycusis and AD is still unknown. By reviewing the relevant literature, we found that the SIRT1-PGC1α pathway and LKB1 (or CaMKKβ)-AMPK pathway may play a role in the preservation of cerebral neuron function by taking part in the regulation of mitochondrial function. Then vascular endothelial growth factor signal pathway is activated to promote vascular angiogenesis and maintenance of the blood–brain barrier integrity. Recently, experiments have also shown that their expression levels are altered in both presbycusis and AD mouse models. Therefore, we propose that exploring the specific molecular link between presbycusis and AD may provide new ideas for their prevention and treatment.

As a stressor widely existing in daily life, noise can cause great alterations to the immune system and result in many physical and mental disorders, including noise-induced deafness, sleep disorders, cardiovascular diseases, endocrine diseases and other problems. The immune system plays a major role in maintaining homeostasis by recognizing and removing harmful substances in the body. Many studies have shown that noise may play vital roles in the occurrence and development of some immune diseases. In humans, both innate immunity and specific immunity can be influenced by noise, and different exposure durations and intensities of noise may exert various effects on the immune system. Short-term or low-intensity noise can enhance immune function, while long-term or high-intensity noise suppresses it. Noise can lead to the occurrence of noise-induced hearing loss (NIHL) through the production of autoantibodies such as anti-Hsp70 and anti-Hsp60 and exert adverse effects related to other immune-related diseases such as some autoimmune diseases and non-Hodgkin lymphoma. The neuroendocrine system, mainly including the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic-adrenal-medullary (SAM) system, is involved in the mechanisms of immune-related diseases induced by noise and gut microbiota dysfunction. In addition, noise exposure during pregnancy may be harmful to the immune system of the fetus. On the other hand, some studies have shown that music can improve immune function and alleviate the adverse effects caused by noise.

Head and neck squamous cell carcinoma (HNSCC) is a highly invasive malignancy with poor survival. Perforin (PRF1) plays essential roles in host immunity. Our research intended to identify the correlations of PRF1 with clinical prognosis and tumor immune infiltration in HNSCC. We explored PRF1 expression and its associations with the clinical features of HNSCC via the Tumor Immune Estimation Resource (TIMER), Oncomine and The Cancer Genome Atlas (TCGA) databases. The prognostic value of PRF1 for HNSCC was further explored by Kaplan-Meier plotter and TIMER. Finally, the relation between PRF1 and immune infiltration in HNSCC was estimated via CIBERSORT and TIMER. PRF1 expression was remarkably elevated in HNSCC and associated with clinical stage and HPV infection. High PRF1 expression predicted favorable outcomes in HNSCC, especially in HPV+ HNSCC. Moreover, higher infiltration of CD8+ T cells and CD4+ T cells were found in the PRF1high group of HNSCC. PRF1 expression in HNSCC was strongly correlated with infiltrating CD8+ T cells and dendritic cells (DCs), with higher relevance in HPV+ HNSCC. Our findings suggested that PRF1 could be a novel prognostic biomarker in HNSCC and that its expression was related to immune cell infiltration, which was impacted by HPV status.

Presbycusis contributes to cognitive decline and Alzheimer's disease. However, most research in this area involves clinical observations and statistical modeling, and few studies have examined the relationship between hearing loss and the molecular changes that lead to cognitive dysfunction. The present study investigated whether hearing loss contributes to dementia in the absence of aging and noise using a mouse model of severe bilateral hearing loss induced by kanamycin (1000 mg/kg) and furosemide (400 mg/kg). Immunohistochemistry, silver staining, immunofluorescence analysis, and Western blotting were used to observe pathological changes in different regions of the hippocampus in animals with hearing loss. Changes in the cognitive function of animals with hearing loss were assessed using the Morris water maze test. The results showed that neurons began to degenerate 60 days after hearing loss, and this degeneration was accompanied by structural disorganization and decreased neurogenesis. The level of phosphorylated tau increased over time. Increases in escape latency and distance traveled during the training phase of the Morris water maze test were observed 90 days after hearing loss. Activated microglia and astrocytes with increased levels of inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were detected in the hippocampus. These results suggest that hearing loss alone causes neuronal degeneration, inhibition of neurogenesis, increased tau protein phosphorylation, and increased neuroinflammation in the hippocampus. Early intervention in individuals with hearing loss may reduce the risk of cognitive decline.

Autophagy, a highly conserved cellular mechanism, plays an essential role in the development and pathology of many central and peripheral nervous system diseases. The auditory system, especially hair cells (HCs) and spiral ganglion neurons (SGNs) in the inner ear, are postmitotic cells, which are extremely reliant on cellular homeostasis and energy supply. Therefore, autophagy may be involved in contributing to and facilitating the normal function of inner ear cells. Recently, studies on hearing loss induced by ototoxic drugs, noise exposure and other factors have revealed that autophagy could serve in an antioxidative capacity and could possess the potential to treat sensorineural hearing loss (SNHL). Therefore, here we review previous studies concerning autophagy and SNHL to gain insight into the role of autophagic mechanisms in inner ear disorders.

Noise-induced hearing loss (NIHL) is characterized by damage to cochlear neurons and associated hair cells; however, a systematic evaluation of NIHL pathogenesis is still lacking. Here, we systematically evaluated differentially expressed genes of 22 cochlear samples in an NIHL mouse model. We performed Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and weighted gene co-expression network analysis (WGCNA). Core modules were detected using protein–protein interactions and WGCNA with functional annotation, diagnostic value evaluation, and experimental validation. Pooled functional annotation suggested the involvement of multiple inflammatory pathways, including the TNF signaling pathway, IL-17 signaling pathway, NF-kappa B signaling pathway, rheumatoid arthritis, and p53 signaling pathway. The core modules suggested that responses to cytokines, heat, cAMP, ATP, mechanical stimuli, and immune responses were important in NIHL pathogenesis. These activities primarily occurred on the external side of the plasma membrane, the extracellular region, and the nucleus. Binding activities, including CCR2 receptor binding, protein binding, and transcription factor binding, may be important. Additionally, the hub molecules with diagnostic value included Relb, Hspa1b, Ccl2, Ptgs2, Ldlr, Plat, and Ccl17. An evaluation of Relb and Hspa1b protein levels showed that Relb was upregulated in spiral ganglion neurons, which might have diagnostic value. In conclusion, this study indicates that the inflammatory response is involved in auditory organ changes in NIHL pathogenesis; moreover, several molecules and activities have essential and subtle influences that have translational potential for pharmacological intervention.