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Lumbar spinal stenosis (LSS) affects over 100 million people globally, with an increasing incidence due to an ageing population. While LSS is known to be heritable, its genetic basis remains poorly understood. We conduct a genome-wide meta-analysis of LSS in 40,303 cases and 741,469 controls. We identify 73 previously unreported loci in addition to 15 known loci, and highlight spinal degeneration as a key pathogenic mechanism. In 12,784 surgically treated cases, we discover five loci...

Neuronal intranuclear inclusion disease is caused by abnormal GGC repeat expansion in the NOTCH2NLC gene, though its pathogenic mechanism remains incompletely understood. This study shows that the abnormally expanded polyG-uN2C protein, encoded by the repeat sequence, contains intrinsically disordered regions and forms aggregates, leading to mislocalization of nucleophosmin and downregulation of fibrillarin. PolyG aggregates interact with nucleophosmin and rRNA, disrupting ribosomal homeostasis....

The E3 ubiquitin ligase HUWE1 modifies a diverse network of substrate proteins by ubiquitination, through which it regulates various intracellular processes and contributes to both oncogenic and tumour suppressor mechanisms in different cancer contexts. Here, by analysing human lung adenocarcinoma (LUAD) patient samples, we reveal that HUWE1 protein expression is commonly upregulated in LUAD tumours compared to normal adjacent lung tissue and that this increase is associated with tumour stage....

Malignant tumors are the leading cause of death in individuals over 65 years old, with metastasis as the primary driver. Emerging evidence suggests that age-related metabolic changes and secreted factors increase the risk of metastasis, but the underlying mechanisms remain unclear. Here we demonstrate in mice that extracellular vesicles (EVs) from senescent hepatocytes promote metastasis across tumor types. We show that aged liver tissue exhibits elevated expression of P2X purinoceptor 7...

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INTRODUCTION: As the age of the world's population continues to increase it is important to investigate behaviors, such as alcohol consumption, that may negatively impact the health of the older population.

We investigated stressful adversities older adults face, examined whether older men and women experience them differently, assessed the stressfulness of these events and studied their relationship to resilience-the ability to overcome adversity. This cross-sectional study included 1179 respondents from the Helsinki Birth Cohort Study, born between 1934 and 1944. At a mean age of 75 years, respondents reported the most stressful adversity in the past five years, its perceived stressfulness and...

Mobility decline with aging is a major health concern, associated with a higher risk for disability. Despite the prevalence of gait slowing in elderly adults, this issue has not been adequately addressed. The central nervous and skeletal muscle systems are key regulators of gait speed. However, direct molecular communication along the brain-muscle axis and their interactions in mobility resilience remain poorly studied. Extracellular vesicles (EVs) have emerged as a key player in long-distance...

The accumulation of senescent cells contributes to age-related inflammation and heightened susceptibility to viral infection. The mechanisms by which cellular senescence and aging exacerbate virus-associated diseases remain poorly understood. Here we show that innate antiviral immunity is progressively impaired with aging in mice, in parallel with systemic accumulation of senescent cells. Mechanistically, senescent cells suppress innate antiviral response mostly via four senescence-associated...

New tool could help researchers probe how models “unlearn” sensitive training material

Curiosity rover finds what may be the first direct evidence that Mars once had a thick atmosphere

Attacks have destroyed or damaged a wide range of academic and commercial research centers

This article aims to comprehensively analyze the vascular factors in Alzheimer's Disease (AD), particularly the changes in the carotid arteries, and their complex correlations with hippocampal atrophy and cognitive function. Besides the traditional β-amyloid protein (Aβ) and Tau protein hypotheses, vascular factors are increasingly regarded as crucial factors in the development of AD. This article systematically reviews the roles of cerebral blood flow perfusion changes and micro-infarctions in...

The accumulation of amyloid β (Aβ) protein in the brain is a central pathological hallmark of Alzheimer's disease (AD). This process has become a major focus of interdisciplinary research and a critical target in drug development. Aβ is produced through the proteolytic processing of amyloid precursor protein (APP) by a group of enzymes known as secretases. They belong to different protease classes and operate through proteolytic cleavage of the peptide bond through several catalytic hydrolysis....

Gait speed is a robust marker of health in older adults and is associated with cognition, yet few studies have examined this in the oldest-old and if there are differences by cognitive domain. We examined the association between gait speed and cognition across three domains in individuals aged 90 + , considering differences by gender and device use. Then, 502 participants were included from the LifeAfter90 Study. Baseline gait speed (meters/second) was measured using the 4-meter walk test. The...