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Amyloid β-dependent neuronal silencing through synaptic decoupling

1 month 3 weeks ago
Amyloid β (Aβ)-dependent circuit dysfunction in Alzheimer's disease (AD) is determined by a puzzling mix of hyperactive and inactive ("silent") brain neurons. Recent studies identified excessive glutamate accumulation as a key Aβ-dependent determinant of hyperactivity. The cellular mechanisms underlying neuronal silence depend on both Aβ and tau protein pathologies, with an unknown role of Aβ. Here, by using single-cell-initiated rabies virus (RV) tracing in mouse models of β-amyloidosis, we...
Yonghai Zhang

PTMs as molecular encoders: reprogramming chaperones into epichaperomes for network control in disease

1 month 3 weeks ago
Recent discoveries reveal that post-translational modifications (PTMs) do more than regulate protein activity - they encode conformational states that transform chaperones into epichaperomes: multimeric scaffolds that rewire protein-protein interaction networks. This emerging paradigm expands the framework of chaperone biology in disease and provides a structural basis for systems-level dysfunction in disorders such as cancer and Alzheimer's disease. This review explores how PTMs within...
Feixia Chu

Enalapril mitigates senescence and aging-related phenotypes in human cells and mice via pSmad1/5/9-driven antioxidative genes

1 month 3 weeks ago
Aging increases the risk of a myriad of chronic diseases, which are expensive and difficult to treat owing to their various risk factors. Repurposing existing medications has accelerated the development of therapies aimed at slowing aging. In this study, using IMR90 cells and aged mice, we revealed that enalapril, a drug widely prescribed for hypertension, can improve both cellular senescence and individual health. Mechanistically, phosphorylated Smad1/5/9 act as pivotal mediators of the...
Wencong Lyu

Genetic influence of the brain on epigenetic age acceleration: evidence of a large-scale genetic correlation study

1 month 3 weeks ago
The relationship between the brain and aging remains unclear. Our objective is to explore the causal connections between brain structure,gene expression, and traits associated with aging. Mendelian randomization(MR) analysis was conducted to explore the associations between brain structures and aging-related traits including GrimAge acceleration(GrimAA), PhenoAge acceleration (PhenoAA), HannumAge acceleration(HannumAA), HorvathAge acceleration(HorvathAA), and leukocyte telomere length(LTL). The...
Chengcheng Li

Reference values for the five-times-sit-to-stand test: a pooled analysis including 45,470 participants from 14 countries

1 month 3 weeks ago
The aim of this study was to establish reference values for the Five-Times-Sit-to-Stand Test (FTSST) in a large, population-representative sample from 14 European countries. Data were collected among 45,470 participants aged 50 + years, as part of the 5th wave of the Survey of Health, Ageing and Retirement in Europe. The reference values for the FTSST were calculated as the 5th, 10th, 20th, 30th, 40th, 50th, 60th, 70th, 80th, 90th, and the 95th weighted percentile. The analyses were stratified...
Jozo Grgic

Distinct roles for NF-kappaB in hematopoietic stem cells and the bone marrow milieu in promoting hematopoietic aging

1 month 3 weeks ago
Hematopoietic aging is characterized by chronic inflammation associated with myeloid bias, hematopoietic stem cell (HSC) accumulation, and functional HSC impairment. Yet it remains unclear how inflammation promotes aging phenotypes. Nuclear factor κB (NF-κB) both responds to and directs inflammation, and we present an experimental model of elevated NF-κB activity ("inhibitor of κB deficient" [IκB^(-)]) to dissect its role in hematopoietic aging phenotypes. We find that while elevated NF-κB...
Jennifer J Chia

A Prominent Pro-Inflammatory Phenotype Is Observed in Replication and Stress-Induced Senescent Mast Cells

1 month 3 weeks ago
Mast cells (MC) are long-lived important immune effectors that control inflammation, allergies, and innate immunity reactions, but the expression of specific markers in replicative and stress-induced senescence in this cell type, together with its relevance in vivo, has not been described. Here, bone marrow-derived MCs (BMMC) were generated from young C57BL6/J mice and kept in culture for a long time or treated with the well-known stressor bacterial lipopolysaccharide (LPS) to promote...
A Ibarra-Sánchez