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Genomic analysis of intracranial and subcortical brain volumes yields polygenic scores accounting for variation across ancestries

2 months ago
Subcortical brain structures are involved in developmental, psychiatric and neurological disorders. Here we performed genome-wide association studies meta-analyses of intracranial and nine subcortical brain volumes (brainstem, caudate nucleus, putamen, hippocampus, globus pallidus, thalamus, nucleus accumbens, amygdala and the ventral diencephalon) in 74,898 participants of European ancestry. We identified 254 independent loci associated with these brain volumes, explaining up to 35% of...
Luis M García-Marín

Sex-dependent interplay of phosphate and inflammation on muscle strength irrespective of muscle mass in middle-aged and older adults

2 months ago
CONCLUSIONS: This study highlights a sex-specific association of inflammation in the mechanisms of hyperphosphatemia-related muscle weakness. The findings emphasize the importance of managing both hyperphosphatemia and chronic inflammation to mitigate their collective impact on muscle function, particularly in older men. Addressing these factors is crucial for promoting muscle health in later life.
Chih-Ping Chung

Curbing household food waste and associated climate change impacts in an ageing society

2 months ago
We explored the intricate quantitative structure of household food waste and their corresponding life cycle greenhouse gas emissions from raw materials to retail utilizing a combination of household- and food-related economic statistics and life cycle assessment in Japan. Given Japan's status as a nation heavily impacted by an aging population, this study estimates these indicators for the six age brackets of Japanese households, showing that per capita food waste increases as the age of the...
Yosuke Shigetomi

Artemisiae Iwayomogii Herba mitigates excessive neuroinflammation and Aβ accumulation by regulating the pro-inflammatory response and autophagy-lysosomal pathway in microglia in 5xFAD mouse model of Alzheimer's disease

2 months ago
Alzheimer's disease (AD) presents a growing societal challenge, driven by an aging population. It is characterized by neurodegeneration linked to β-amyloid (Aβ) and tau protein aggregation. Reactive glial cell-mediated neuroinflammation exacerbates disease progression by facilitating the accumulation of Aβ and impairing its clearance, thus highlighting potential therapeutic targets. Aerial parts of Artemisia iwayomogi (AIH), a kind of mugwort, has been consumed as a medicinal herb in East Asia...
In Gyoung Ju

Investigating the influence of the SIRT6 gene and alternative splicing on canine longevity: an in-depth bioinformatics analysis and experimental confirmation via NGS-based targeted sequencing

2 months ago
Sirtuin 6 (SIRT6) has many functions, but its most notable contribution lies in the intricate regulation of cell senescence and lifespan. The effect of the SIRT6 gene on body size and longevity in dogs has not been extensively studied, particularly with regard to alternative splicing mechanisms. To address this gap, the present study used a comprehensive approach that integrated bioinformatics analysis, DNA sequence analysis, and next-generation sequencing-based targeted sequencing analyses. Our...
Özge Özmen

Multi-parametric thrombus profiling microfluidics detects intensified biomechanical thrombogenesis associated with hypertension and aging

2 months ago
Arterial thrombosis is a leading cause of death and disability worldwide with no effective bioassay for clinical prediction. As a symbolic feature of arterial thrombosis, severe stenosis in the blood vessel creates a high-shear, high-gradient flow environment that facilitates platelet aggregation towards vessel occlusion. Here, we present a thrombus profiling assay that monitors the multi-dimensional attributes of thrombi forming in such biomechanical conditions. Using this assay, we demonstrate...
Misbahud Din

Calorie restriction increases insulin sensitivity to promote beta cell homeostasis and longevity in mice

2 months ago
Caloric restriction (CR) can extend the organism life- and health-span by improving glucose homeostasis. How CR affects the structure-function of pancreatic beta cells remains unknown. We used single nucleus transcriptomics to show that CR increases the expression of genes for beta cell identity, protein processing, and organelle homeostasis. Gene regulatory network analysis reveal that CR activates transcription factors important for beta cell identity and homeostasis, while imaging...
Cristiane Dos Santos

Cell senescence in cardiometabolic diseases

2 months ago
Cellular senescence has been implicated in many age-related pathologies including atherosclerosis, heart failure, age-related cardiac remodeling, diabetic cardiomyopathy and the metabolic syndrome. Here, we will review the characteristics of senescent cells and their endogenous regulators, and summarize the metabolic stressors that induce cell senescence. We will discuss the evidence of cell senescence in the onset and progression of several cardiometabolic diseases and the therapeutic potential...
Mandy O J Grootaert

Genomic analysis of intracranial and subcortical brain volumes yields polygenic scores accounting for variation across ancestries

2 months ago
Subcortical brain structures are involved in developmental, psychiatric and neurological disorders. Here we performed genome-wide association studies meta-analyses of intracranial and nine subcortical brain volumes (brainstem, caudate nucleus, putamen, hippocampus, globus pallidus, thalamus, nucleus accumbens, amygdala and the ventral diencephalon) in 74,898 participants of European ancestry. We identified 254 independent loci associated with these brain volumes, explaining up to 35% of...
Luis M García-Marín

WDR20 prevents hepatocellular carcinoma senescence by orchestrating the simultaneous USP12/46-mediated deubiquitination of c-Myc

2 months ago
The dysfunction of the ubiquitin-proteasome system (UPS) facilitates the malignant progression of hepatocellular carcinoma (HCC). While targeting the UPS for HCC therapy has been proposed, identifying effective targets has been challenging. In this study, we conducted a focused screen of siRNA libraries targeting UPS-related WD40 repeat (WDR) proteins and found that silencing WDR20, a deubiquitinating enzyme activating factor, selectively inhibited the proliferation of HCC cells without...
Li Jiang