scholarly journals Progress and Prospects in Human Genetic Research into Age-Related Hearing Impairment

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Yasue Uchida ◽  
Saiko Sugiura ◽  
Michihiko Sone ◽  
Hiromi Ueda ◽  
Tsutomu Nakashima
Keyword(s):  
Hearing Impairment ◽  
Stress Responses ◽  
Preventive Intervention ◽  
Genetic Research ◽  
Interindividual Variation ◽  
Extrinsic Factors ◽  
Age Related ◽  
Tremendous Progress ◽  
Sizable Proportion ◽  
Human Genetic Research

Age-related hearing impairment (ARHI) is a complex, multifactorial disorder that is attributable to confounding intrinsic and extrinsic factors. The degree of impairment shows substantial variation between individuals, as is also observed in the senescence of other functions. This individual variation would seem to refute the stereotypical view that hearing deterioration with age is inevitable and may indicate that there is ample scope for preventive intervention. Genetic predisposition could account for a sizable proportion of interindividual variation. Over the past decade or so, tremendous progress has been made through research into the genetics of various forms of hearing impairment, including ARHI and our knowledge of the complex mechanisms of auditory function has increased substantially. Here, we give an overview of recent investigations aimed at identifying the genetic risk factors involved in ARHI and of what we currently know about its pathophysiology. This review is divided into the following sections: (i) genes causing monogenic hearing impairment with phenotypic similarities to ARHI; (ii) genes involved in oxidative stress, biologic stress responses, and mitochondrial dysfunction; and (iii) candidate genes for senescence, other geriatric diseases, and neurodegeneration. Progress and prospects in genetic research are discussed.

scholarly journals Sensory Loss and the Healthcare System: Outcomes and Navigation

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 797-797
Author(s):  
Nicholas Reed ◽  
Charlotte Yeh
Keyword(s):  
Health Care ◽  
Hearing Impairment ◽  
Hearing Aids ◽  
Quality Care ◽  
Vision Impairment ◽  
Sensory Loss ◽  
Sensory Impairment ◽  
Age Related ◽  
Increased Risk ◽  
National Quality

Abstract Communication is fundamental to patient-centered care. However, sensory impairment limits communication among older adults. Specifically, hearing impairment strains communication via degraded auditory encoding while vision impairment distresses ability to read and interpret visual cues. The presence of dual sensory impairment, defined as concurrent hearing and vision impairment, may exacerbate these effects. The potential consequence s of age-related sensory loss on health care interactions and outcomes are beginning to surface in epidemiologic studies demonstrating poorer patient-provider communication, higher medical expenditures, increased risk of 30-day readmission, and longer length of stay when compared to individuals without sensory loss. Importantly, these associations may be amenable to intervention via sensory aids; however, uptake to sensory care is low. Notably, less than 20% of persons with hearing impairment have hearing aids and over 55% of Medicare Beneficiaries with reported vision problems have not had an eye examination in the prior year. Affordability and access may contribute to lack of sensory care uptake as Medicare explicitly excludes coverage of vision and hearing services. In this symposium, we will review current and new evidence for whether sensory loss affects health care outcomes, including satisfaction with care, incident delirium during hospitalization, navigation of Medicare, and present data on how persons with sensory loss are more likely to delay their care independent of cost and insurance factors suggesting fundamental changes in health care system interaction. We will place these results within the context of current national quality care and policy initiatives and review methods to address sensory loss.

scholarly journals Pancreatic Ductal Adenocarcinoma Arising in Young and Old Patients Displays Similar Molecular Features

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1234
Author(s):  
Jérôme Raffenne ◽  
Fernando A. Martin ◽  
Rémy Nicolle ◽  
Marina Konta ◽  
Yuna Blum ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stress Responses ◽  
Protein Identification ◽  
Molecular Profile ◽  
Global Methylation ◽  
Old Patients ◽  
Molecular Features ◽  
Age Related ◽  
Clinical Difference ◽  
Dna Repair Gene

Pancreatic ducal adenocarcinoma is classically diagnosed in the 7th decade, but approximately 10% of patients are diagnosed under 55 years (y.o.). While the genomic and transcriptomic landscapes of late-onset tumors (LOT) have been described, little is known about early-onset tumors (EOT). Ageing is known to impact DNA methylation and proteome integrity through carbonylation-related oxidative damages. We therefore aimed to assess the global molecular features of EOT. We compared 176 EOT (≤55 y.o.) and 316 LOT (≥70 y.o.) from three distinct surgical cohorts at the clinical/genomic/epigenomic/transcriptomic level. Furthermore, we assessed oxidative stress responses and oxidative proteome damages using 2D gel electrophoresis followed by mass spectrometry protein identification. There was no consistent clinical difference between EOT and LOT across the three cohorts. The mutational landscape of key driver genes and the global methylation profile were similar in the two groups. LOT did display age-related features such as enriched DNA repair gene signatures and upregulation of oxidative stress defenses together with increased proteome carbonylation. However, these age-related differences were more preeminent in non-tumor tissues while tumor proteome and proteome damages were fairly comparable. In conclusion, this multi-omics comparison showed that EOT harbor a comparable molecular profile to that of LOT.

scholarly journals Accelerated aging in normal breast tissue of women with breast cancer

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Shoghag Panjarian ◽  
Jozef Madzo ◽  
Kelsey Keith ◽  
Carolyn M. Slater ◽  
Carmen Sapienza ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Methylation ◽  
Anomaly Detection ◽  
Breast Tissue ◽  
Preventive Intervention ◽  
Normal Breast Tissue ◽  
Accelerated Aging ◽  
Normal Breast ◽  
Age Related ◽  
Unsupervised Anomaly Detection

Abstract Background DNA methylation alterations have similar patterns in normal aging tissue and in cancer. In this study, we investigated breast tissue-specific age-related DNA methylation alterations and used those methylation sites to identify individuals with outlier phenotypes. Outlier phenotype is identified by unsupervised anomaly detection algorithms and is defined by individuals who have normal tissue age-dependent DNA methylation levels that vary dramatically from the population mean. Methods We generated whole-genome DNA methylation profiles (GSE160233) on purified epithelial cells and used publicly available Infinium HumanMethylation 450K array datasets (TCGA, GSE88883, GSE69914, GSE101961, and GSE74214) for discovery and validation. Results We found that hypermethylation in normal breast tissue is the best predictor of hypermethylation in cancer. Using unsupervised anomaly detection approaches, we found that about 10% of the individuals (39/427) were outliers for DNA methylation from 6 DNA methylation datasets. We also found that there were significantly more outlier samples in normal-adjacent to cancer (24/139, 17.3%) than in normal samples (15/228, 5.2%). Additionally, we found significant differences between the predicted ages based on DNA methylation and the chronological ages among outliers and not-outliers. Additionally, we found that accelerated outliers (older predicted age) were more frequent in normal-adjacent to cancer (14/17, 82%) compared to normal samples from individuals without cancer (3/17, 18%). Furthermore, in matched samples, we found that the epigenome of the outliers in the pre-malignant tissue was as severely altered as in cancer. Conclusions A subset of patients with breast cancer has severely altered epigenomes which are characterized by accelerated aging in their normal-appearing tissue. In the future, these DNA methylation sites should be studied further such as in cell-free DNA to determine their potential use as biomarkers for early detection of malignant transformation and preventive intervention in breast cancer.

scholarly journals Screening tools for the identification of dementia for adults with age-related acquired hearing or vision impairment: a scoping review

2017 ◽  
Vol 29 (11) ◽  
pp. 1771-1784 ◽  
Author(s):  
Annie Pye ◽  
Anna Pavlina Charalambous ◽  
Iracema Leroi ◽  
Chrysoulla Thodi ◽  
Piers Dawes
Keyword(s):  
Hearing Impairment ◽  
Cognitive Assessment ◽  
Negative Impact ◽  
Sensory Modality ◽  
Vision Impairment ◽  
Assessment Tools ◽  
Screening Tools ◽  
Screening Tests ◽  
Cognitive Screening ◽  
Age Related

ABSTRACTBackground:Cognitive screening tests frequently rely on items being correctly heard or seen. We aimed to identify, describe, and evaluate the adaptation, validity, and availability of cognitive screening and assessment tools for dementia which have been developed or adapted for adults with acquired hearing and/or vision impairment.Method:Electronic databases were searched using subject terms “hearing disorders” OR “vision disorders” AND “cognitive assessment,” supplemented by exploring reference lists of included papers and via consultation with health professionals to identify additional literature.Results:1,551 papers were identified, of which 13 met inclusion criteria. Four papers related to tests adapted for hearing impairment; 11 papers related to tests adapted for vision impairment. Frequently adapted tests were the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MOCA). Adaptations for hearing impairment involved deleting or creating written versions for hearing-dependent items. Adaptations for vision impairment involved deleting vision-dependent items or spoken/tactile versions of visual tasks. No study reported validity of the test in relation to detection of dementia in people with hearing/vision impairment. Item deletion had a negative impact on the psychometric properties of the test.Conclusions:While attempts have been made to adapt cognitive tests for people with acquired hearing and/or vision impairment, the primary limitation of these adaptations is that their validity in accurately detecting dementia among those with acquired hearing or vision impairment is yet to be established. It is likely that the sensitivity and specificity of the adapted versions are poorer than the original, especially if the adaptation involved item deletion. One solution would involve item substitution in an alternative sensory modality followed by re-validation of the adapted test.

scholarly journals Expression levels of the BAK1 and BCL2 genes highlight the role of apoptosis in age-related hearing impairment

2016 ◽  
pp. 1003 ◽  
Author(s):  
Masoumeh Falah ◽  
Mohammad Najafi ◽  
Massoud Houshmand ◽  
Mohammad Farhadi
Keyword(s):  
Hearing Impairment ◽  
Expression Levels ◽  
Age Related

scholarly journals Inhibition of 11β-HSD1 Ameliorates Cognition and Molecular Detrimental Changes after Chronic Mild Stress in SAMP8 Mice

2021 ◽  
Vol 14 (10) ◽  
pp. 1040
Author(s):  
Dolors Puigoriol-Illamola ◽  
Júlia Companys-Alemany ◽  
Kris McGuire ◽  
Natalie Z. M. Homer ◽  
Rosana Leiva ◽  
...  
Keyword(s):  
Stress Responses ◽  
Healthy Aging ◽  
Molecular Mechanisms ◽  
Chronic Mild Stress ◽  
Mild Stress ◽  
Cognitive Improvement ◽  
Age Related ◽  
Mtorc1 Signaling ◽  
Cognitive Disturbances ◽  
Samp8 Mice

Impaired glucocorticoid (GC) signaling is a significant factor in aging, stress, and neurodegenerative diseases such as Alzheimer’s disease. Therefore, the study of GC-mediated stress responses to chronic moderately stressful situations, which occur in daily life, is of huge interest for the design of pharmacological strategies toward the prevention of neurodegeneration. To address this issue, SAMP8 mice were exposed to the chronic mild stress (CMS) paradigm for 4 weeks and treated with RL-118, an 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitor. The inhibition of this enzyme is linked with a reduction in GC levels and cognitive improvement, while CMS exposure has been associated with reduced cognitive performance. The aim of this project was to assess whether RL-118 treatment could reverse the deleterious effects of CMS on cognition and behavioral abilities and to evaluate the molecular mechanisms that compromise healthy aging in SAMP8 mice. First, we confirmed the target engagement between RL-118 and 11β-HSD1. Additionally, we showed that DNA methylation, hydroxymethylation, and histone phosphorylation were decreased by CMS induction, and increased by RL-118 treatment. In addition, CMS exposure caused the accumulation of reactive oxygen species (ROS)-induced damage and increased pro-oxidant enzymes—as well as pro-inflammatory mediators—through the NF-κB pathway and astrogliosis markers, such as GFAP. Of note, these modifications were reversed by 11β-HSD1 inhibition. Remarkably, although CMS altered mTORC1 signaling, autophagy was increased in the SAMP8 RL-118-treated mice. We also showed an increase in amyloidogenic processes and a decrease in synaptic plasticity and neuronal remodeling markers in mice under CMS, which were consequently modified by RL-118 treatment. In conclusion, 11β-HSD1 inhibition through RL-118 ameliorated the detrimental effects induced by CMS, including epigenetic and cognitive disturbances, indicating that GC-excess attenuation shows potential as a therapeutic strategy for age-related cognitive decline and AD.

scholarly journals Antioxidant Effects of Caffeic Acid Lead to Protection of Drosophila Intestinal Stem Cell Aging

2021 ◽  
Vol 9 ◽  
Author(s):  
Xiao Sheng ◽  
Yuedan Zhu ◽  
Juanyu Zhou ◽  
La Yan ◽  
Gang Du ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Caffeic Acid ◽  
Stress Responses ◽  
Adult Stem Cells ◽  
Cell Function ◽  
Cell Aging ◽  
Positive Effects ◽  
Age Related ◽  
Tissue Aging

The dysfunction or exhaustion of adult stem cells during aging is closely linked to tissue aging and age-related diseases. Circumventing this aging-related exhaustion of adult stem cells could significantly alleviate the functional decline of organs. Therefore, identifying small molecular compounds that could prevent the age-related decline of stem cell function is a primary goal in anti-aging research. Caffeic acid (CA), a phenolic compound synthesized in plants, offers substantial health benefits for multiple age-related diseases and aging. However, the effects of CA on adult stem cells remain largely unknown. Using the Drosophila midgut as a model, this study showed that oral administration with CA significantly delayed age-associated Drosophila gut dysplasia caused by the dysregulation of intestinal stem cells (ISCs) upon aging. Moreover, administering CA retarded the decline of intestinal functions in aged Drosophila and prevented hyperproliferation of age-associated ISC by suppressing oxidative stress-associated JNK signaling. On the other hand, CA supplementation significantly ameliorated the gut hyperplasia defect and reduced environmentally induced mortality, revealing the positive effects of CA on tolerance to stress responses. Taken together, our findings report a crucial role of CA in delaying age-related changes in ISCs of Drosophila.

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