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Trends and mechanisms of Alzheimer's disease and hearing impairment: A 20-year perspective
Alzheimer's disease (AD) and hearing loss (HL) are major age-related public health challenges with emerging evidence suggesting their interconnection. This study aimed to investigate global research trends, shared molecular mechanisms, and clinical implications of AD and HL. A total of 349 articles published between 2004 and 2024 were retrieved from the Web of Science Core Collection and analyzed using VOSviewer and CiteSpace. GeneCards and STRING databases were used to explore molecular targets...
Sequential transcriptional programs underpin activation of hippocampal stem cells
Adult neural stem cells exist on a continuum from deep to shallow quiescence that changes in response to injury or aging; however, the transcription factors controlling these stepwise transitions have not been identified. Single-cell transcriptomic analyses of mice with loss of function or increased levels of the essential activation factor Ascl1 reveal that Ascl1 promotes the activation of hippocampal neural stem cells by driving these cells out of deep quiescence, despite its low protein...
Biological age acceleration in Alzheimer's disease modulates relative cortical to medial temporal lobe neurodegeneration
Alzheimer's disease (AD) is highly associated with aging, typically presenting with amnestic, multi-domain cognitive impairment and greater medial temporal lobe (MTL) atrophy relative to cortex. However, approximately 15 % of AD cases present atypically, often at younger ages and with greater cortical involvement relative to MTL. This association between age and AD presentation is imperfect: some younger-onset cases are typical, amnestic presentations while some older-onset cases present less...
Trends and mechanisms of Alzheimer's disease and hearing impairment: A 20-year perspective
Alzheimer's disease (AD) and hearing loss (HL) are major age-related public health challenges with emerging evidence suggesting their interconnection. This study aimed to investigate global research trends, shared molecular mechanisms, and clinical implications of AD and HL. A total of 349 articles published between 2004 and 2024 were retrieved from the Web of Science Core Collection and analyzed using VOSviewer and CiteSpace. GeneCards and STRING databases were used to explore molecular targets...
Using RNA therapeutics to promote healthy aging
Aging is characterized by a gradual decline of cellular and physiological functions over time and an increased risk of different diseases. RNA therapeutics constitute an emerging approach to target the molecular mechanisms of aging and age-related diseases via rational design and have several advantages over traditional drug therapies, including high specificity, low toxicity and the potential for rapid development and production. Here, we discuss the latest developments in RNA therapeutics...
Epigenetic aging mediates the association between life course socioeconomic status and decrements in kidney function across a decade
Epigenetic aging measures are novel molecular indicators of biological aging that predict age-related chronic disease. We examined whether several established indices of epigenetic aging mediated the association between life course socioeconomic status (SES) and decrements in kidney function across a decade. Biomarker data were from 252 non-Hispanic (NH) Black and white participants who had consented to genetic analyses in Wave 2 (2004-2009) and 3 (2014-2021) of the Midlife in the United States...
A mathematical model that predicts human biological age from physiological traits identifies environmental and genetic factors that influence aging
Why people age at different rates is a fundamental, unsolved problem in biology. We created a model that predicts an individual's age from physiological traits that change with age in the large UK Biobank dataset, such as blood pressure, lung function, strength, and stimulus-reaction time. The model predicted a person's age with best accuracy when it heavily weighted traits that together query multiple organ systems, arguing that most or all physiological systems (lung, heart, brain, etc.)...
R-2-hydroxyglutarate-mediated inhibition of KDM4A compromises telomere integrity
Mutation, deletion, or silencing of genes encoding cellular metabolism factors occurs frequently in human malignancies. Neomorphic mutations in isocitrate dehydrogenases 1 and 2 (IDH1/2) promoting the production of R-2-hydroxyglutarate (R-2HG) instead of α-ketoglutarate (αKG) are recurrent in human brain cancers and constitute an early event in low-grade gliomagenesis. Due to its structural similarity with αKG, R-2HG acts as an inhibitor of αKG-dependent enzymes. These include the JUMONJI family...
The compensatory effect of education as revealed by resting-state electroencephalographic alpha rhythms in patients with dementia due to Parkinson's disease: findings from an exploratory study
Here, we investigated whether educational attainment influences the neurophysiological mechanisms underlying vigilance regulation, as reflected in resting-state eyes-closed electroencephalographic (rsEEG) rhythms, in patients with dementia due to Parkinson's (PDD) and Lewy body disease (DLB). Clinical, demographic, and rsEEG data were obtained from an international database, including PDD patients (N = 75), DLB patients (N = 50), and cognitively unimpaired older controls (Healthy; N = 54). Each...
Transglutaminase 2-mediated glutamine deamidation enhances p21 stability during senescence
The limited doubling capacity of human cells, known as replicative senescence or cellular senescence, is a major factor in cellular aging. This process is triggered by telomere erosion, which activates a p53-mediated DNA damage response (DDR) that halts cell proliferation. p53, a transcriptional regulator, responds to DNA damage by increasing the expression of the cyclin-dependent kinase inhibitor p21. p21 then arrests cells at specific stages of the cell cycle. Additionally, p53 upregulates...
Understanding the Impact of Mutations in the Cystathionine Beta-Synthase Gene: Towards Novel Therapeutics for Homocystinuria
Protein misfolding and conformational instability drive protein conformational disorders, causing either accelerated degradation and loss-of-function, as in inherited metabolic disorders like lysosomal storage disorders, or toxic aggregation and gain-of-function, as in neurodegenerative diseases like Alzheimer's disease or amyotrophic lateral sclerosis. Classical homocystinuria (HCU), an inborn error of sulfur amino acid metabolism, results from cystathionine beta-synthase (CBS) deficiency. CBS...
Muscle Mitochondrial Respiration and Cardiorespiratory Fitness Contribute to Slower Walking Speed of Older Individuals Who Identify as Black
In the United States, older adults who self-identify as Black have a disproportionately higher incidence of mobility disability compared to those who are White. Whether older adults who are Black also have lower fitness and mitochondrial energetics has not been adequately investigated. The study of muscle, mobility and aging (SOMMA) examined 879 participants aged ≥ 70 years old, including 116 who self-identified as Black. Mitochondrial respiration (Max OXPHOS) was measured in permeabilized...