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Insulin signaling in microglia: A metabolic switch controlling neuroinflammation and amyloid pathology in Alzheimer's disease

5 months 4 weeks ago
Insulin resistance is a risk factor for Alzheimer's disease (AD). Chen et al.¹ show that microglial insulin signaling is essential for metabolic homeostasis and immune regulation, while insulin resistance impairs Aβ clearance and promotes neuroinflammation in AD. Their findings reframe AD pathogenesis through a cell-type-specific lens.
Eugenio Barone

Lithium deficiency and the onset of Alzheimer's disease

5 months 4 weeks ago
The earliest molecular changes in Alzheimer's disease (AD) are poorly understood^(1-5). Here we show that endogenous lithium (Li) is dynamically regulated in the brain and contributes to cognitive preservation during ageing. Of the metals we analysed, Li was the only one that was significantly reduced in the brain in individuals with mild cognitive impairment (MCI), a precursor to AD. Li bioavailability was further reduced in AD by amyloid sequestration. We explored the role of endogenous Li in...
Liviu Aron

Cellular senescence in skeletal diseases: A bibliometric analysis from 2007 to 2024

5 months 4 weeks ago
CONCLUSION: Research in this field has garnered substantial attention in recent years. This bibliometric analysis not only underscores the correlation between cellular senescence and skeletal diseases, but also highlights that targeting cellular senescence and the SASP may offer potential therapeutic strategies. These findings can inform future research directions and the development of targeted interventions for age-related skeletal conditions.
Xuanrui Zhang

Mechanobiology of the blood-brain barrier during development, disease and ageing

5 months 4 weeks ago
The blood-brain barrier (BBB) preserves brain health through selective permeability, and its disruption is a hallmark of many neurological disorders. Mechanical stimuli such as shear stress and cyclic strain are increasingly recognised to influence BBB integrity and function, while alterations in tissue stiffness and extracellular matrix composition contribute to its breakdown during ageing and disease. Despite its importance, BBB mechanobiology remains underexplored. Here we highlight the...
Simon Konig

Aging affects reprogramming of pulmonary capillary endothelial cells after lung injury in male mice

5 months 4 weeks ago
Aging increases the risk of developing fibrotic diseases by hampering tissue regeneration after injury. Using longitudinal single-cell RNA-seq and spatial transcriptomics, here we compare the transcriptome of bleomycin (BLM) -induced fibrotic lungs of young and aged male mice, at 3 time points corresponding to the peak of fibrosis, regeneration, and resolution. We find that lung injury shifts the transcriptomic profiles of three pulmonary capillary endothelial cells (PCEC) subpopulations. The...
Marin Truchi

Lithium deficiency and the onset of Alzheimer's disease

5 months 4 weeks ago
The earliest molecular changes in Alzheimer's disease (AD) are poorly understood^(1-5). Here we show that endogenous lithium (Li) is dynamically regulated in the brain and contributes to cognitive preservation during ageing. Of the metals we analysed, Li was the only one that was significantly reduced in the brain in individuals with mild cognitive impairment (MCI), a precursor to AD. Li bioavailability was further reduced in AD by amyloid sequestration. We explored the role of endogenous Li in...
Liviu Aron

Age-related alterations in alpha and beta oscillations support preservation of semantic processing in healthy aging

5 months 4 weeks ago
Semantic processing remains relatively preserved during healthy aging, but the mechanisms are poorly understood. Herein, we use dynamic functional mapping based on magnetoencephalography to examine the neural oscillations serving semantic processing across the adult lifespan (N = 154; 21-87 years). Task-related oscillatory dynamics were imaged using a beamformer and whole-brain linear mixed-effects (LME) models were calculated with age and task condition (semantically-related or -unrelated) as...
Megan C Hall

Quantitative and sensitive sequencing of somatic mutations induced by a maize transposon

5 months 4 weeks ago
Cells accumulate mutations throughout development, contributing to cancer, aging, and evolution. Quantitative data on the abundance of de novo mutations within plants or animals are limited, as new mutations are often rare within a tissue and fall below the limits of current sequencing depths and error rates. Here, we show that mutations induced by the maize Mutator (Mu) transposon can be reliably quantified down to a detection limit of 1 part in 16,000. We measured the abundance of millions of...
Justin Scherer

Allele frequency selection and no age-related increase in human oocyte mitochondrial mutations

5 months 4 weeks ago
Mitochondria, cellular powerhouses, harbor DNA [mitochondrial DNA (mtDNA)] inherited from the mothers. mtDNA mutations can cause diseases, yet whether they increase with age in human oocytes remains understudied. Here, using highly accurate duplex sequencing, we detected de novo mutations in single oocytes, blood, and saliva in women 20 to 42 years of age. We found that, with age, mutations increased in blood and saliva but not in oocytes. In oocytes, mutations with high allele frequencies were...
Barbara Arbeithuber

Simultaneous imaging of bidirectional guided waves probes arterial mechanical anisotropy, blood pressure, and stress synchronously

5 months 4 weeks ago
Arterial biomechanical indicators have long been recognized as fundamental contributors to the physiology and pathology of cardiovascular systems. Probing multiple biomechanical parameters of arteries simultaneously throughout the cardiac cycle is highly important but remains challenging. Here, we report a method to quantify arterial anisotropic stiffness, arterial wall stresses, and local blood pressure in a single measurement. With programmed ultrasound excitation and imaging, arterial axial...
Yuxuan Jiang

Hematopoietic loss of Y chromosome activates immune checkpoints and contributes to impaired senescent cell clearance and renal disease

5 months 4 weeks ago
The accumulation of senescent cells contributes to morbidity and mortality; however, common mechanisms underpinning this age-associated phenomenon remain elusive. Hematopoietic loss of the Y chromosome (LOY) is the most frequently acquired somatic mutation in males, and this condition has been associated with various age-associated diseases and reduced lifespan. Therefore, we investigated the role of hematopoietic LOY in promoting cellular senescence, focusing on kidney disease because of its...
Yohei Arai

A Metabolite Score of Unintentional Weight Loss Explained a Substantial Proportion of Associated Mortality and Mobility Limitation Risk in a Biracial Older Cohort

5 months 4 weeks ago
Unintentional weight loss (UWL) is related to mortality and mobility limitation. Here, we aimed to develop a metabolite-based score for UWL and evaluate its prediction performance and explanation value for UWL-related health outcomes. Participants from the Health, Aging and Body Composition (Health ABC) study with available metabolomics and valid follow-ups were included (N = 2286). First, in the derivation group (N = 1200), 27 of the 77 metabolites associated with incident UWL (> 3% annual UWL...
Shanshan Yao

EnsembleAge: enhancing epigenetic age assessment with a multi-clock framework

5 months 4 weeks ago
Several widely used epigenetic clocks have been developed for mice and other species, but a persistent challenge remains: different mouse clocks often yield inconsistent results. To address this limitation in robustness, we present EnsembleAge, a suite of ensemble-based epigenetic clocks. Leveraging data from over 200 perturbation experiments across multiple tissues, EnsembleAge integrates predictions from multiple penalized models. Empirical evaluations demonstrate that EnsembleAge outperforms...
Amin Haghani