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Landscape of copy number variants in Spanish people with dementia

1 day ago
Recent studies suggest that copy number variants (CNVs) may contribute to the missing heritability of complex diseases such as Alzheimer's disease (AD) and related dementias (ADRD). We performed a CNV analysis using genotyping data (Axiom 815 K Spanish biobank array) from the GR@ACE/DEGESCO dementia dataset (n = 20,067) of the Spanish population. Applying PennCNV and extensive quality control, 8275 controls and 7818 dementia cases were selected for gene-level case/control associations. We...
Itziar de Rojas

Select microbial metabolites promote tau aggregation in a murine tauopathy model

1 day ago
The gut microbiome is emerging as a modifier of risk for neurodegenerative diseases, but underlying mechanisms remain poorly understood. Here, we show that the hTau.P301S mouse model for progressive tauopathy develops alterations in the composition and function of the gut microbiome that are not recapitulated in amyloid-based 5xFAD or 3xTg models for Alzheimer's disease. Disrupting the gut microbiome via chronic antibiotic treatment exacerbates cognitive deficits and tau pathology in hTau.P301S...
Sabeen A Kazmi

Digital Technologies for Healthy Longevity: A Policy Agenda from the Einstein Circle on Inclusive, Data-Driven Ageing Societies

1 day ago
BACKGROUND: Rapid population ageing presents one of the defining global health challenges of the twenty-first century. While digital technologies are increasingly used to support older adults, their deployment often remains fragmented, inequitable, and insufficiently guided by ethical and legal frameworks. This paper proposes an integrated policy agenda for healthy longevity, based on the interdisciplinary work of the Einstein Circle Longevity - Healthy Ageing Assisted by Digital Technologies.
Katarina Braune

Bidirectional Relationship and Shared Mechanisms Between Sarcopenia and Osteoporosis: An Observational Study Integrating Genomic, Proteomic, and Metabolomic Data

1 day ago
With global population aging, sarcopenia and osteoporosis have become critical public health challenges. Muscles and bones are closely interconnected anatomically and functionally, but the biological mechanisms connecting sarcopenia and osteoporosis have not yet been fully elucidated. This study systematically investigated the bidirectional relationship and shared mechanisms between sarcopenia and osteoporosis through multi-omics analysis integrating genomic, proteomic, and metabolomic data from...
Siqi Xu

Role of Klhl14 in senescence and epithelial-to-mesenchymal transition via TGF-beta modulation

1 day ago
KLHL14, a component of an E3-ubiquitin ligase complex, has emerged as a context-dependent oncogene or tumor suppressor, particularly important for thyroid development. Yet its role in thyroid biology remains largely unexplored. In this study, we uncover a central function for KLHL14 in maintaining thyroid epithelial identity and regulating tissue homeostasis. Using a thyroid organoid model, we show that KLHL14 is essential for the proper growth and maturation of thyroid cells. Reduction of...
Rufina Maturi

Age-related changes in behavioural and neural variability in a decision-making task

1 day ago
Age-related cognitive decline in learning and decision-making may arise from increased variability of neural responses. Here, we investigated how ageing affects behavioural and neural variability by recording >18,000 neurons across 16 brain regions (including cortex, hippocampus, thalamus, midbrain, and basal ganglia) in younger and older mice performing a visual decision-making task. Older mice showed more variable response times, reproducing a common finding in human ageing studies. Ageing...
Fenying Zang

Lineage tracing from cellular heritage to disease destiny

1 day ago
The developmental history of a cell fundamentally defines its identity and function. Recent advances in cell lineage tracing now enable high-resolution reconstruction of cellular ancestries in vivo, illuminating how lineage dictates fate in health and disease. This Review highlights recently developed tools, ranging from refined recombinase systems to advanced synthetic and natural barcoding approaches, that facilitate the investigation of pathological lineage programs in cancer, cardiovascular...
Huan Zhu

Immunotherapy with B28, an antibody to Aβ oligomers, potently decreases amyloid plaques, microgliosis, and memory decline in APP knock-in mice

1 day ago
Immunotherapy against amyloid β-protein (Aβ) for Alzheimer's disease (AD) has been widely approved. Breakthrough disease-modifying treatments such as lecanemab and donanemab are often followed by drugs with improved efficacy. By immunizing Trianni mice with aggregated synthetic Aβ, we obtained B28, a fully human antibody specifically selected for its neutralization of tau neuritic dystrophy induced by AD brain-derived oligomers. In a blinded trial in mutant human APP^(NL-G-F) knock-in mice,...
Ting Yang

A scalable, dividing cell model for the robust propagation and quantification of human sporadic Creutzfeldt-Jakob disease prions

1 day ago
Prion diseases represent a unique biological paradigm with mechanistic parallels to other neurodegenerative conditions like Alzheimer's and Parkinson's diseases. However, the study of human prion pathobiology and the development of effective therapeutics has been severely constrained by the inability to propagate human prions in dividing cells-forcing reliance on costly and slow animal bioassays. Here, we report the generation of EKV cells-a humanized cell model which supports the robust,...
Akin Nihat

Tau protein as a regulator of mitochondrial function and dynamics

1 day ago
Mitochondrial damage is a shared hallmark of brain aging and neurodegeneration. While pathological Tau mutations disrupt mitochondrial dynamics and function, the physiological role of wild-type (WT) Tau in the maintenance of mitochondrial homeostasis remains poorly understood. Here, using Caenorhabditis elegans and mice lacking PTL-1, the nematode Tau-like homolog, and Tau respectively, we demonstrate that Tau deficiency promotes a shift toward a pro-fusion mitochondrial state associated with...
Eleni Tsakiri

The influence of aging on graded peripheral venous return and complex blood flow features through human veins

1 day ago
Aging is associated with reduced venous compliance and altered muscle pump function, though how these features impact venous return during volume-stressed conditions remains poorly characterized. We examined lower-limb venous flow dynamics and muscle pump efficiency between healthy younger (YA) and older adults (OA) under two volume-stressed conditions. Fourteen YA (7F, 26 ± 4 years) and fourteen OA (9F, 76 ± 6 years) underwent assessments at head-down tilt (HDT, -3°) and head-up tilt (HUT, +...
Jeremy N Cohen

A Gut-Centric View of Ageing: A Pilot Analysis Mapping Age-Associated Immune and Molecular Alterations in Colonic Mucosa Using Spatial Proteomics

1 day ago
Investigating age-associated changes in intestine and understanding immune-related intestinal dysfunctions is essential for promoting healthy ageing. Mucosal surfaces represent a distinct immune compartment enriched with specialised lymphocytes that interact dynamically with the epithelial layer. In this study, we present novel spatially resolved insights into the cellular and molecular alterations in the ageing murine gut mucosa. Our findings reveal a complex network of interdependent...
Jack Sullivan

Clonal Analyses Reveal the Impact of Hematopoietic Stem and Progenitor Cell Aging on T Cell Development

1 day ago
T cell output from the thymus falls throughout life and is associated with profound remodeling of the thymic stroma. To what extent the decline in T cell output is caused by aging of the hematopoietic stem and progenitor cells (HSPCs) has been difficult to define because of HSPC heterogeneity, the multi-stage process of HSPC migration, and the cross-talk between hematopoietic and stromal elements of the thymus. To address the contribution of HSPC aging on T cell development, we interrogated T...
Julia Gensheimer

High-saturated-fat diet drives female-biased neurodegeneration in <em>Drosophila</em> via oxidative stress and impaired autophagic flux

1 day ago
CONCLUSION: These findings identify oxidative stress and disrupted autophagy as key mediators of saturated-fat-induced neuronal decline and highlight a sex-specific vulnerability to dietary fat composition. This work establishes Drosophila as a powerful model for dissecting nutritional drivers of neural aging and suggests that metabolic stress pathways represent critical early targets in diet-associated neurodegeneration.
A M Taylor