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Functional characterisation of rare variants in genes encoding the MAPK/ERK signalling pathway identified in long-lived Leiden Longevity Study participants

3 months 2 weeks ago
Human longevity, which is coupled to compression of age-related disease, is a heritable trait. However, only few common genetic variants have been linked to longevity, suggesting that rare, family-specific variants may also play a role. We therefore investigated whole-genome sequencing data of long-lived individuals from the Leiden Longevity Study and identified family-specific variants residing in genes involved in the mitogen-activated protein kinase (MAPK) cascade, a lifespan-associated and...
Maarouf Baghdadi

Trends and driving factors of age-related hearing loss and severity over 30 years: a cross-sectional study

3 months 2 weeks ago
CONCLUSION: The global burden of AHL continues to rise, which is a growing problem for countries with medium SDI levels. Occupational noise exposure emerges as a critical modifiable risk factor, particularly in rapidly industrializing economies, highlighting the urgent need to prioritize workplace hearing protection programs and targeted noise control policies tailored to regional contexts. These interventions are especially vital for older men in low-resource settings and medically underserved...
Fen-Fen Li

β-synuclein blocks α-synuclein condensate fusion to disrupt the maturation of phase separation

3 months 2 weeks ago
The abnormal accumulation of α-synuclein (α-Syn) is a key feature of Parkinson's disease (PD) and other synucleinopathies. α-Syn undergoes liquid-liquid phase separation (LLPS) to accelerate the amyloid aggregation. β-synuclein (β-Syn) colocalizes with α-Syn and affects its aggregation. It remains poorly understood how the LLPS of α-Syn is regulated by β-Syn. Here, we find that β-Syn co-condenses with α-Syn, negatively regulating the LLPS of α-Syn. The mobility of α-Syn is reduced in α-Syn/β-Syn...
Bingkuan Xu

Predicting and preventing Alzheimer's disease

3 months 2 weeks ago
With all the advances in both the science of aging and artificial intelligence (AI), we are in a propitious position to accurately and precisely determine who is at high risk of developing Alzheimer's disease years before signs of even mild cognitive deficit. It takes at least 20 years for aggregates of misfolded β-amyloid and tau proteins to accumulate in the brain along with neuroinflammation that they incite. This provides a long window of opportunity to get ahead of the pathobiological...
Eric Topol

Single-nucleus profiling of mouse inner ear aging uncovers cell type heterogeneity and hair cell subtype-specific age-related signatures

3 months 2 weeks ago
Degeneration of the auditory and vestibular hair cells (HCs) leads to dysfunction of two essential senses: hearing loss and decompensated balance perception. However, the cellular and molecular mechanisms governing inner ear aging and its link to dysfunctions of sensory HCs remain unclear. Here, we constructed an aging-associated cell atlas of cochlear and utricular tissues in C57BL/6J mice through single-nucleus RNA sequencing, revealing transcriptionally distinct hair cell subtypes and...
Mingyu Xia

Predicting and preventing Alzheimer's disease

3 months 2 weeks ago
With all the advances in both the science of aging and artificial intelligence (AI), we are in a propitious position to accurately and precisely determine who is at high risk of developing Alzheimer's disease years before signs of even mild cognitive deficit. It takes at least 20 years for aggregates of misfolded β-amyloid and tau proteins to accumulate in the brain along with neuroinflammation that they incite. This provides a long window of opportunity to get ahead of the pathobiological...
Eric Topol

Modifiable risk factor profiles moderate the effect of beta-amyloid pathology on cognition in aging

3 months 2 weeks ago
Although modifiable risk factors may account for around 40 % of population variability in dementia risk, the effect of risk factor interrelationships on pathology-cognition relationships is poorly understood. Using risk factor data from a cohort of 203 cognitively normal older adults (73 ± 6.4 years, 56 % female), we used k-means clustering to assign participants to one of three risk-related profiles; namely, positive-active (physical/cognitive activity, education), positive-affective (sleep,...
Mohini Bhade

On the patterns of genetic intra-tumour heterogeneity before and after treatment

3 months 2 weeks ago
Genetic intra-tumour heterogeneity (gITH) is a universal property of all cancers. It emerges from the interplay of cell division, mutation accumulation and selection with important implications for the evolution of treatment resistance. Theoretical and data-driven approaches extensively studied gITH in ageing somatic tissues or cancers at detection. Yet, the expected patterns of gITH during and after treatment are less well understood. Here, we use stochastic birth-death processes to investigate...
Alexander Stein

Intermittent Supplementation With Fisetin Improves Physical Function and Decreases Cellular Senescence in Skeletal Muscle With Aging: A Comparison to Genetic Clearance of Senescent Cells and Synthetic Senolytic Approaches

3 months 2 weeks ago
Excess cellular senescence contributes to age-related increases in frailty and reductions in skeletal muscle strength. In the present study, we determined the efficacy of oral intermittent treatment (1 week on-2 weeks off-1 week on) with the natural flavonoid senolytic fisetin to improve frailty and grip strength in old mice. Further, the effects of fisetin on physical function were evaluated in young mice. We performed bulk RNA sequencing of quadricep skeletal muscle to determine the cell...
Kevin O Murray

Research status of visuospatial dysfunction and spatial navigation

3 months 2 weeks ago
Visuospatial function is a critical aspect of cognitive abilities, encompassing visual perception, attention, memory, and adaptive responses to spatial changes. This paper reviews studies on human visuospatial function, spatial navigation, and factors contributing to visuospatial impairments. After introducing fundamental concepts of visuospatial function and spatial navigation, classical methods for assessing visuospatial performance are summarized. By examining recent advances in spatial...
Rui Bao

Intervention strategies for Parkinson's disease: the role of exercise and mitochondria

3 months 2 weeks ago
Parkinson's disease (PD), a progressive neurodegenerative disorder with complex pathogenic mechanisms, exhibiting rising prevalence alongside global population aging. Its pathological hallmarks include substantial loss of dopaminergic neurons in the substantia nigra pars compacta, leading to motor symptoms (e.g., bradykinesia, rigidity) and non-motor manifestations (e.g., cognitive impairment, sleep disorders). Accumulating evidence underscores mitochondrial dysfunction-encompassing reactive...
Ganggang Xu