Vulnerability to chronic stress and the phenotypic heterogeneity of presbycusis with subjective tinnitus

Abstract

Age-related functional reserve decline and vulnerability of multiple physiological systems and organs, as well as at the cellular and molecular levels, result in different frailty phenotypes, such as physical, cognitive, and psychosocial frailty, and multiple comorbidities, including age-related hearing loss (ARHL) and/or tinnitus due to the decline in auditory reserve. However, the contributions of chronic non-audiogenic cumulative exposure, and chronic audiogenic stress to phenotypic heterogeneity of presbycusis and/or tinnitus remain elusive. Because of the cumulative environmental stressors throughout life, allostasis systems, the hypothalamus-pituitary-adrenal (HPA) and the sympathetic adrenal–medullary (SAM) axes become dysregulated and less able to maintain homeostasis, which leads to allostatic load and maladaptation. Brain–body communication via the neuroendocrine system promotes systemic chronic inflammation, overmobilization of energetic substances (glucose and lipids), and neuroplastic changes via the non-genomic and genomic actions of glucocorticoids, catecholamines, and their receptors. These systemic maladaptive alterations might lead to different frailty phenotypes and physical, cognitive, and psychological comorbidities, which, in turn, cause and exacerbate ARHL and/or tinnitus with phenotypic heterogeneity. Chronic audiogenic stressors, including aging accompanying ontological diseases, cumulative noise exposure, and ototoxic drugs as well as tinnitus, activate the HPA axis and SAM directly and indirectly by the amygdala, promoting allostatic load and maladaptive neuroplasticity in the auditory system and other vulnerable brain regions, such as the hippocampus, amygdala, and medial prefrontal cortex (mPFC). In the auditory system, peripheral deafferentation, central disinhibition, and tonotopic map reorganization may trigger tinnitus. Cross-modal maladaptive neuroplasticity between the auditory and other sensory systems is involved in tinnitus modulation. Persistent dendritic growth and formation, reduction in GABAergic inhibitory synaptic inputs induced by chronic audiogenic stresses in the amygdala, and increased dendritic atrophy in the hippocampus and mPFC, might involve the enhancement of attentional processing and long-term memory storage of chronic subjective tinnitus, accompanied by cognitive impairments and emotional comorbidities. Therefore, presbycusis and tinnitus are multisystem disorders with phenotypic heterogeneity. Stressors play a critical role in the phenotypic heterogeneity of presbycusis. Differential diagnosis based on biomarkers of metabonomics study, and interventions tailored to different ARHL phenotypes and/or tinnitus will contribute to healthy aging and improvement in the quality of life.

Mushrooms as Functional Foods for Ménière’s Disease

“…Ménière's disease patients, exposed to chronic stress, also have significantly decreased hippocampal volume, interrelated with memory and key clinical, vascular, and genetic risk factors, which is consistent with severity hyperacusis and vestibular balance disorders of the affected side [121,122].…”

The potassium channels: Neurobiology and pharmacology of tinnitus

“…Fortunately, the heterogeneity of tinnitus has received increasing attention in recent years. The grouping of people with tinnitus in the trial should take into account the symptom dimension (Mohan et al., 2022), brain imaging data (Henton & Tzounopoulos, 2021; Riha et al., 2020), audiogenic or non‐audiogenic stressors (Ruan et al., 2022), tinnitus severity and related comorbidities (Beukes et al., 2021), and so on. It could lead to personalized treatment and precision medicine approach (Tzounopoulos et al., 2019).…”

Presbycusis: A Coordinated and Personalized Approach According to Different Frailty Phenotypes

“…It is estimated that 20-26% of adults aged 45 years and increasing to 63% in adults older than 70 years, and nearly 80% of people over 85 years have hearing loss [1][2][3]. ARHL is characterized by central auditory processing deficit (CAPD), including temporal processing and frequency resolution, and greater auditory speech perception challenges, apart from different degrees of peripheral hearing loss [4], and often associated with presbyastasis, subjective tinnitus or hyperacusis, and physical, cognitive, and psychological disorders [5][6][7][8]. The interaction of aging and internal and external environment factors results in different pathological alterations and heterogeneous clinical phenotypes.…”

“…The interaction of aging and internal and external environment factors results in different pathological alterations and heterogeneous clinical phenotypes. Aging causes gradually increasing decline of multi-system physiological reserve [7]. Some external environmental factors, such as environmental enrichment, including educational, occupational, or leisure activities, are beneficial for the improvement of cognitive and auditory reserves, and active physical exercise for the improvement of multi-system physiological reserves.…”

“…Some external environmental factors, such as environmental enrichment, including educational, occupational, or leisure activities, are beneficial for the improvement of cognitive and auditory reserves, and active physical exercise for the improvement of multi-system physiological reserves. More environmental factors are harmful for health, referred as to stressors, including physical, physiological, psychosocial, and unhealthy lifestyles [7]. Local audiogenic stressors and otological diseases can cause auditory reserve decline, the imbalance of auditory system homeostasis, and hearing loss with tinnitus.…”