Dietary restriction reduces age-related degeneration of stria vascularis in the inner ear of the rat

We report here beneficial effects of life-long dietary restriction on the progression of age-associated cochlear degeneration in female Sprague–Dawley rats. Thirty-month old rats on a 70% dietary restriction were compared to ad libitum fed age-matched rats, and three-month old adult rats. As expected, aged dietary restricted rats displayed about 20% higher survival rate than age-matched rats fed ad libitum. This difference was reflected also in the auditory system. In the dietary restricted group, 73% of the subjects had preserved auditory reflexes (Preyer), and only modest degeneration of the stria vascularis of the inner ear was observed. In contrast, aged ad libitum fed animals, of which only 15% had detectable Preyer reflexes, showed a marked thinning, cellular degeneration and loss of cell processes in the stria vascularis. The extent of loss of sensory hair cells (~ 24%) was similar in both the aged groups, and neither group showed a significant reduction in the number of spiral ganglion neurons across adult life-span. The observations thus demonstrate that dietary restriction delays age-related degradation of the auditory system. The results provide further insights into the mechanisms of strial presbycusis.     

Aging cochleas in the F344 rat: morphological and functional changes

The Fischer 344 rat strain has been frequently used as an animal model of rapid aging. The present study was aimed at evaluating the incidence of apoptotic cells in the inner ear of 20-24-month-old F344 rats and to correlate it with cochlear function using otoacoustic emissions. Staining with cresyl violet and the enzymatic labeling (terminal deoxynucleotidyl transferase, TdT) of fragmented DNA revealed large numbers of apoptotic cells in the marginal and basal layers of the stria vascularis and in adjacent cells of the spiral ligament. The amplitudes of distortion products otoacoustic emissions (DPOAEs), which reflect functional state of the outer hair cells, were significantly reduced or totally absent in these animals. In contrast to old F344 rats, no marked DPOAE amplitude reduction and smaller numbers of apoptotic cells were found in young 4-month-old F344 rats or in aged 24-28-month-old Long Evans rats. The accumulation of apoptotic cells, mainly in the basal layer of the stria vascularis and in adjacent cells of the spiral ligament, leads to a detachment of the stria vascularis from the spiral ligament and results in the impairment of outer hair cell function. This specific type of strial deterioration suggests that aged F344 rats can serve as an animal model of strial presbycusis.     

Hearing loss is a risk factor of disability in older adults: A systematic review

Background and ObjectivesHearing loss (HL) is a public health problem affecting older adults. HL is not only a health condition but also a complex, dynamic phenomenon related to disability. Previous studies identified associations between HL and undesirable outcomes; however, their correlation remains inconclusive. Hearing loss can have profound impact on daily life in the elderly, and an understanding of how HL contributes to disability is needed. A systematic review was conducted to comprehensively examine current evidence and determine the association between HL and disability regarding impairment, activity and participation in older adults.Research Design and MethodsThe Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines were applied in this systematic review. Quality assessment was conducted using the Newcastle-Ottawa Scale for longitudinal studies and the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for cross-sectional studies.ResultsIn this systematic review of 20 studies, HL was associated with mobility limitation, activity limitation and participation restriction. The severity of HL was associated with impaired mobility and physical performance, but the association was only found in persons with severe/major HL. HL was also associated with activities of daily living (ADL) dependency, however these findings were mainly based on cross-sectional studies.Discussion and ImplicationsHL is related to disability by impairment, activity limitations or participation restrictions in older adults. Future studies should include participation restrictions as a mediation factor to better understand this association. Consistent and accurate hearing measurements and hearing loss criteria are also required to determine the impact of HL on disability.     

Absence of insulin signalling in skeletal muscle is associated with reduced muscle mass and function: evidence for decreased protein synthesis and not increased degradation

Loss of skeletal muscle mass and function is observed in many insulin-resistant disease states such as diabetes, cancer cachexia, renal failure and ageing although the mechanisms for this remain unclear. We hypothesised that impaired insulin signalling results in reduced muscle mass and function and that this decrease in muscle mass and function is due to both increased production of atrogenes and aberrant reactive oxygen species (ROS) generation. Maximum tetanic force of the extensor digitorum longus of muscle insulin receptor knockout (MIRKO) and lox/lox control mice was measured in situ. Muscles were removed for the measurement of mass, histological examination and ROS production. Activation of insulin signalling pathways, markers of muscle atrophy and indices of protein synthesis were determined in a separate group of MIRKO and lox/lox mice 15 min following treatment with insulin. Muscles from MIRKO mice had 36% lower maximum tetanic force generation compared with muscles of lox/lox mice. Muscle fibres of MIRKO mice were significantly smaller than those of lox/lox mice with no apparent structural abnormalities. Muscles from MIRKO mice demonstrated absent phosphorylation of AKT in response to exogenous insulin along with a failure to phosphorylate ribosomal S6 compared with lox/lox mice. Atrogin-1 and MuRF1 relative mRNA expression in muscles from MIRKO mice were decreased compared with muscles from lox/lox mice following insulin treatment. There were no differences in markers of reactive oxygen species damage between muscles from MIRKO mice and lox/lox mice. These data support the hypothesis that the absence of insulin signalling contributes to reduced muscle mass and function though decreased protein synthesis rather than proteasomal atrophic pathways.     

Second-line injectable induced ototoxicity in drug resistant tuberculosis: A systematic review of Indian studies

Second-line injectables (SLIs) form an essential class of agents in the treatment of drug resistant (DR) tuberculosis (TB). However, their use is sometimes limited due to serious adverse events like ototoxicity and hearing loss, leading to permanent hearing loss if SLIs are continued. Globally as well as in India a wide variation in incidence of ototoxicity/hearing loss has been reported in patients with DR-TB. In this systematic analysis, we attempt to ascertain the ototoxicity of SLIs in Indian patients with multidrug resistant tuberculosis (MDR-TB) wherein ototoxicity onset was assessed using audiometry performed at both pre- and post-SLI treatment initiation. Twenty two studies were identified based on the inclusion criteria. Ototoxicity was observed in 10.12% [349/3447] patients within 3.8 ± 2.6 months of treatment initiation when the ototoxicity was assessed either with or without audiometry assessment. Only five studies reported ototoxicity assessment with PTA at both pre- and post-SLI initiation and ototoxicity was observed in 27.01% (121/448) patients in these five studies. Sensorineural loss was observed in three studies (high frequency loss: capreomycin, 25.0% [1/4 patients]; amikacin, 19.7% [12/61]; kanamycin, 13.3% [22/166]; streptomycin, 11.8% [2/17]; flat loss: amikacin, 8.2% [5/61]; streptomycin, 5.9% [1/17]; kanamycin 4.8% [8/166]). Most of the patients experiencing ototoxicity were managed by discontinuing (49.6% [120/242]) or replacing SLI treatment (40.8% [49/120]). The study identified high prevalence of ototoxicity in Indian patients with DR-TB treated with SLI when ototoxicity was monitored regularly using PTA (27.01%), warranting a need to develop unified guidelines for monitoring ototoxicity, improving physician awareness and educating patients/caregivers for reporting symptoms of hearing loss.     

铁必复颗粒治疗老年性聋的临床疗效与分子机制研究

目的观察铁必复颗粒治疗老年性聋的临床疗效,通过实验探讨该方对肾虚耳聋治疗作用的分子机制。方法老年性聋患者136例,随机分两组,铁必复颗粒组70例（138耳）,西药对照组66例（129耳）,前者接受铁必复颗粒冲服,后者口服尼莫地平等。实验研究选用Wistar大鼠120只,随机分为两组。正常对照大鼠组,喂标准饲料16W;缺铁大鼠组,采用缺铁饲料喂养8W后,再分成肾虚耳聋组、铁必复颗粒组,肾虚耳聋组继续喂以缺铁饲料8W,铁必复颗粒治疗组喂以添加铁必复颗粒的缺铁饲料8W。取大鼠耳蜗膜性组织进行蛋白质组学分析,比较各组蛋白质表达差异。结果老年性聋患者铁必复颗粒组显效21耳,有效42耳,有效率45．65％;西药对照组有效10耳,有效率7．75％,前者有效率高于后者,两组疗效差异有统计学意义（P〈0．01）。实验研究表明,肌动蛋白、肌球蛋白、细胞骨架蛋白等在铁必复颗粒治疗组耳蜗膜性组织中高表达,与正常组和肾虚耳聋组相比,蛋白表达都有上调。铁必复颗粒组出现特异性高表达46kDaprotein、48kDaprotein等尚未命名的蛋白。结论铁必复颗粒治疗老年性聋有效,其作用机制可能与调控耳蜗肌动、肌球、细胞骨架蛋白等的表达水平有关。     

Genetics of alcoholism: a review of recent studies in human and animal models

There is substantial evidence for a significant genetic component to the risk of alcoholism. In searching for genes that contribute to this risk, several approaches may be utilized in order to identify the genetic loci underlying alcoholism susceptibility. Several candidate genes have been evaluated for their role in alcoholism; however, with the exception of the enzymes of alcohol metabolism, results from these studies have been inconsistent. Recently, two large studies have employed a genome screen methodology to identify novel genes contributing to the risk of alcoholism. As an alternative strategy, researchers have utilized mouse and rat models to identify quantitative trait loci influencing alcohol preference. Through the development of congenic lines and transgenic and knock-out animals, candidate genes can be identified and evaluated for their role in alcohol preference.     

Otological manifestations of acute leukaemia: report of two cases and review of literature

Otological manifestations exceptionally reveal acute leukaemia, whereas leukaemic infiltration of any tissue is frequent at postmortem examination. We present two cases of acute myeloblastic leukaemia revealed by a loss of hearing due to a middle‐ear leukaemic infiltration. The characteristics of such a clinical and radiological finding are emphasized. It is suggested that middle and inner ear can be a ‘sanctuary’ localization, which might sometimes require radiation therapy to achieve durable and complete remission.     

Assessment and management of hearing loss in older people in Belgium,Portugal and Turkey

Hearing loss, usually due to presbycusis, is frequent in old age and goes often undetected or untreated. Older subjects with hearing loss have increasing communication problems, reduced quality of life, isolation, depression and also feelings of frustration and discouragement. Hearing loss is also linked to cardiovascular problems, depression and dementia. Despite its relevance, country-level epidemiological data on age-related incidence and prevalence of presbycusis are limited, and no specific data in different geriatric settings are usually available. Population screening programs similar to those in infants are not widely implanted, although both primary care providers and geriatricians have incorporated strategies to detect hearing loss. No guidelines are available on when and how to screen and manage hearing loss in old age. Management of presbycusis is usually directed by ENT specialists, in cooperation with audiologist. These may be hospital-based or work in for profit centres, depending on the country. Funding of hearing aids by health care providers is limited, so some patients do not have access to them due to their high cost. Attitudes towards hearing loss, including considering it an inevitable age-related problem, may also limit access to care. Cochlear implants are still anecdotal in older patients in most countries. There is still a long way to go in the detection and management of hearing loss in older people. Systematic screening, careful assessment and treatment guidelines will have to be developed and implemented, both at country and European level.     

Analysis of gene expression during aging of CGNs in culture: implication of SLIT2 and NPY in senescence

Senescence is the major key factor that leads to the loss of neurons throughout aging. Cellular senescence is not the consequence of single cause, but there are multiple aspects which may induce senescence in a cell. Various causes such as gene expression, molecular interactions and protein processing and chromatin organization are described as causal factor for senescence. It is well known that the damage to the nuclear or mitochondrial DNA contributes to the aging either directly by inducing the apoptosis/cellular senescence or indirectly by altering cellular functions. The significant nuclear DNA damage with the age is directly associated with the continuous declining in DNA repair. The continuous decline in expression of topoisomerase 2 beta (Topo IIβ) in cultured cerebellar granule neurons over time indicated the decline in the repair of damage DNA. DNA Topo IIβ is an enzyme that is crucial for solving topological problems of DNA and thus has an important role in DNA repair. The enzyme is predominantly present in non-proliferating cells such as neurons. In this paper, we have studied the genes which were differentially expressed over time in cultured cerebellar granule neurons (CGNs) and identified potential genes associated with the senescence. Our results showed that the two genes neuropeptide Y (Npy) and Slit homolog 2 (Drosophila) (Slit2) gradually increase during aging, and upon suppression of these two genes, there was gradual increase in cell viability along with restoration of the expression of Topo IIβ and potential repair proteins.

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老年人听力障碍筛查量表结合畸变产物耳声发射诊断早期老年性聋

目的 研究老年人听力障碍筛查量表（HHIE）与畸变产物耳声发射（DPOAE）联合应用在早期老年性聋诊断中的作用。方法 对2013年5月至2014年10月在解放军总医院海南分院就诊的95例（男51例，女44例）年龄＞65周岁，听力下降＞1年的双耳感音神经性听力下降患者行纯音测听、声阻抗测试、DPOAE检查并填写HHIE。结果 11例纯音测听为轻度听力损失的患者HHIE平均为（30.1±5.0）分，其中1例≥43分，为重度听力障碍，占9.1%（1/11），DPOAE检出率81.8%，阈值（61.3±7.0）dB SPL；23例纯音测听为中度听力损失的患者HHIE平均为（35.6±4.0）分，其中3例≥43分，为重度听力障碍，占13.0%（3/23），DPOAE 检出率78.3%，阈值（68.3±5.0）dB SPL；34例纯音测听为中重度听力损失的患者HHIE平均为（39.3±6.0）分，其中12例≥43分，为重度听力障碍，占35.3%（12/34），DPOAE检出率52.9%，阈值（71.3±5.0）dB SPL；18例纯音测听为重度听力损失的患者HHIE平均（61.7±2.0）分，均为重度听力障碍，DPOAE检出率11.1%，阈值（80.4±3.0）dB SPL；9例纯音测听为极重度听力损失的患者HHIE平均（89.7±5.0）分，均为重度听力障碍，DPOAE检出率0.0%。结论 纯音测听不能全面真实反映老年性聋患者的听力障碍程度，HHIE结合DPOAE对诊断早期老年性聋具有重要意义。     

Impact of hearing difficulty on dependence in activities of daily living (ADL) and mortality: A 3-year cohort study of community-dwelling Japanese older adults

Studies have associated hearing impairment with adverse health outcomes, but the actual impact of hearing difficulty has been barely investigated. We investigated among older adults (i) the prevalence of hearing difficulty, (ii) the association of hearing difficulty with a composite outcome of dependence in activities of daily living (ADL) and death, and (iii) the population attributable risk fraction (PAF) of hearing difficulty. In 2005, a home-visit survey of 1364 Japanese older adults aged ≥65 (participation proportion = 95.5%) was conducted to evaluate self-reports of hearing difficulty. Over 3 years, 99.4% of the initial sample was followed. Outcomes were measured by incidence of death or dependence in ADL. In the sample, the prevalence of hearing difficulty was 17.7% (age ≥65) and 25.7% (age ≥75). Hearing difficulty at high levels was associated with a composite outcome of dependence in ADL and mortality (adjusted odds ratio = OR and 95% confidence interval = 95% CI = 6.19 (1.92-19.92)) as well as with each outcome independently. Improving the hearing difficulty from high to moderate or no difficulty would reduce the composite outcome in 4.3% (age ≥65) and in 6.3% (age ≥75) of the target population. In conclusion, hearing difficulty was common, was associated with and had substantial impact on adverse health outcomes.     

Obesity and central obesity as risk factors for incident dementia and its subtypes: a systematic review and meta-analysis

While dementia affects 6–10% of persons 65 years or older, industrialized countries have witnessed an alarming rise in obesity. However, obesity's influence on dementia remains poorly understood. We conducted a systematic review and meta‐analysis. PUBMED search (1995–2007) resulted in 10 relevant prospective cohort studies of older adults (40–80 years at baseline) with end points being dementia and predictors including adiposity measures, such as body mass index (BMI) and waist circumference (WC). There was a significant U‐shaped association between BMI and dementia (P = 0.034), with dementia risk increased for obesity and underweight. Pooled odds ratios (OR) and 95% confidence intervals (CI) for underweight, overweight and obesity compared with normal weight in relation to incident dementia were: 1.36 (1.07, 1.73), 0.88 (0.60, 1.27) and 1.42 (0.93, 2.18) respectively. Pooled ORs and 95% CI for obesity and incident Alzheimer's disease (AD) and vascular dementia were 1.80 (1.00, 3.29) vs. 1.73 (0.47, 6.31) and were stronger in studies with long follow‐up (>10 years) and young baseline age (<60 years). Weight gain and high WC or skin‐fold thickness increased risks of dementia in all included studies. The meta‐analysis shows a moderate association between obesity and the risks for dementia and AD. Future studies are needed to understand optimal weight and biological mechanisms.     

Association between self-reported hearing impairment,use of a hearing aid and performance of instrumental activities of daily living

Background and purposeAge-related hearing loss is a prevalent condition among the growing elderly population, which has been associated with both cognitive decline and decreased daily functioning. Decreased functioning is linked to lower performance, predominantly regarding instrumental activities of daily living (IADLs). The present study aims to explore the association between hearing loss and impairment in IADLs.MethodsThis is a secondary analysis of The Health, Well-Being, and Aging Colombia study, performed in 2015. Participants were classified into three groups: 1) without hearing loss, 2) hearing loss corrected through the use of a hearing aid, and 3) hearing loss without a hearing aid. Bivariate and adjusted multivariate analyses were performed. The measured outcome was IADLs.Results and discussionInformation from a total of 23,694 community-dwelling Colombian older adults (age ≥ 60 years) was used. The prevalence of hearing impairment was 23.4%, 1.8% out of those reported the use of hearing aids. Independent associations were found for having impaired IADLs when comparing participants with hearing loss without a hearing aid and those with normal hearing. However, there was no statistical significance with respect to IADLs when comparing hearing loss corrected by hearing aids versus participants with normal hearing. Participants using hearing aids have better functioning evaluated by IADLs when compared with participants with hearing impairment and no hearing aids.ConclusionThis study evidences a positive association between hearing impairment and performance in the IADLs. This association is not significant in older adults using hearing aids     

Moderate hearing loss is related with social frailty in a community-dwelling older adults: The Korean Frailty and Aging Cohort Study (KFACS)

ObjectivesTo determine whether hearing loss is associated with social frailty in older adults.MethodsCross-sectional analysis of cohort study data. Hearing was measured using of Pure-tone audiometry. Hearing loss was determined based on the average of hearing thresholds at 0.5, 1, and 2 kHz in the ear that had better hearing. Social frailty was defined based on the summation of the following 5 social components (1. Neighborhood meeting attendance 2. Talking to friend(s) sometimes 3.Someone gives you love and affection 4. Living alone 5. Meeting someone every day). Participants who had no correspondence to the components were considered non-social frailty; those with 1–2 components were considered social prefrailty; and those having 3 or more components were considered social frailty.ResultsThe prevalence of non-social frailty, social prefrailty, social frailty was 27.6%, 60.7% and 11.7% respectively. Of the five questions, two components (Neighborhood meeting attendance and Presence of someone who shows love and affection to the participants) were associated with hearing loss (p < 0.001). Compared to non-social frailty, the odds ratio of social frailty for hearing loss was 2.24 (95% CI 1.48–3.38) after adjusting for age, residential area, economic status, smoking, depressive disorder and MMSE, and 2.17 (95% CI 1.43–3.30) after further adjustments with physical frailty.ConclusionHearing loss was associated with social frailty even after controlling confounding factors even including physical frailty.     

Effects of age simulation suits on psychological and physical outcomes: a systematic review

Age simulation suits (ASS) are widely used to simulate sensory and physical restrictions that typically occur as people age. This review has two objectives: first, we synthesize the current research on ASS in terms of the observed psychological and physical effects associated with ASS. Second, we analyze indicators able to estimate the validity of ASS in simulating “true” ageing processes. Following the PRISMA guidelines, eight electronic databases were searched (BASE, Cinhal, Cochrane, Google Scholar, ProQuest, PsychINFO, Pubmed, and Web of Science). Qualitative and quantitative studies addressing effects of ASS interventions regarding psychological outcomes (i.e., empathy, attitudes) or physical parameters (i.e., gait, balance) were included. The Mixed Methods Appraisal Tool was applied for quality assessment. Of 1890 identified citations, we included 94 for full-text screening and finally 26 studies were examined. Publication years ranged from 2001 to 2021. Study populations were predominantly based on students in health-related disciplines. Results suggest that ASS can initiate positive effects on attitudes toward (d_weighted = 0.33) and empathy for older adults (d_weighted = 0.54). Physical performance was significantly reduced; however, there is only little evidence of a realistic simulation of typical ageing processes. Although positive effects of ASS are supported to some extent, more diverse study populations and high-quality controlled designs are needed. Further, validation studies examining whether the simulation indeed reflects “real” ageing are needed and should build on reference data generated by standardized geriatric assessments or adequate comparison groups of older adults.Prospero registration: 232686.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10433-022-00722-1.     

HCV animal models: a journey of more than 30 years

In the 1970s and 1980s it became increasingly clear that blood transfusions could induce a form of chronic hepatitis that could not be ascribed to any of the viruses known to cause liver inflammation. In 1989, the hepatitis C virus (HCV) was discovered and found to be the major causative agent of these infections. Because of its narrow tropism, the in vivo study of this virus was, especially in the early days, limited to the chimpanzee. In the past decade, several alternative animal models have been created. In this review we review these novel animal models and their contribution to our current understanding of the biology of HCV.     

Animal models of cardiorenal syndrome: a review

The incidence of heart failure and renal failure is increasing and is associated with poor prognosis. Moreover, these conditions do often coexist and this coexistence results in worsened outcome. Various mechanisms have been proposed as an explanation of this interrelation, including changes in hemodynamics, endothelial dysfunction, inflammation, activation of renin-angiotensin-aldosterone system, and/or sympathetic nervous system. However, the exact mechanisms initializing and maintaining this interaction are still unknown. In many experimental studies on cardiac or renal dysfunction, the function of the other organ was either not addressed or the authors failed to show any decline in its function despite histological changes. There are few studies in which the dysfunction of both heart and kidney function has been described. In this review, we discuss animal models of combined cardiorenal dysfunction. We show that translation of the results from animal studies is limited, and there is a need for new and better models of the cardiorenal interaction to improve our understanding of this syndrome. Finally, we propose several requirements that a new animal model should meet to serve as a tool for studies on the cardiorenal syndrome.