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The Role of EVs in the Aging Hematopoietic System
Extracellular vesicles (EVs) are membrane-enclosed nanoparticles that mediate intercellular communication by transferring proteins, nucleic acids, and lipids. Within the hematopoietic system, EVs orchestrate critical signaling between bone marrow (BM) niche cells and hematopoietic stem and progenitor cells (HSPCs) to regulate quiescence, proliferation, and lineage commitment. During aging, senescence and telomere attrition drive a profound remodeling of EV biogenesis and cargo. Aged EVs,...
Mapping the Landscape of AgeTech Standards and Guidelines: A Gray Literature Review
CONCLUSIONS: Although AgeTech standardization is advancing, critical gaps remain. Limited attention to safety, security, privacy, and digital economy and community inclusion raises concerns for trust, equity, and sustainable adoption. Addressing these gaps through targeted and coordinated standardization efforts is essential to support inclusive, trustworthy, and scalable AgeTech solutions in the context of rapid global population aging.
More REM sleep linked to lower risk of 83 diseases
A large study tracking more than 95,000 people suggests that how you sleep may be linked to your risk of developing dozens of diseases. People who spent more time in REM sleep had lower risks of 83 conditions, including dementia, heart failure, and Parkinson’s disease, while more deep sleep was associated with lower risks of conditions such as type 2 diabetes and major depression.
GLP-1 weight loss and diabetes drugs linked to nutritional deficiencies in nearly 1 in 6 children
Children taking GLP-1 medications (such as Victoza, Saxenda, Trulicity, and Ozempic) for weight loss, prediabetes, or type 2 diabetes may face an overlooked risk: nutritional deficiencies. A new study found that nearly 1 in 6 young patients developed a diagnosed deficiency within a year of starting treatment, with vitamin D deficiency affecting about 12%.
Rare pregnancy infections may triple the risk of autism
A major Swedish study of 3.7 million people has found that rare TORCH infections passed from a pregnant woman to the fetus are linked to much higher risks of autism and intellectual disability later in life. Children with a congenital TORCH infection were about three times more likely to be diagnosed with autism, more than seven times more likely to have an intellectual disability, and up to 30 times more likely to have severe to profound intellectual disability.
Breakthrough drug reverses skin aging and dramatically speeds healing
A topical drug that removes aging, damaged cells helped older mice heal skin wounds significantly faster. The treatment appeared to reactivate repair pathways involved in inflammation, collagen production, and new blood vessel growth.
Can an AI feel pain? It can at least act like it does
Study reignites debate over what, if anything, machines can feel
Personalized single-cell transcriptomics reveals molecular diversity in Alzheimer's disease
Alzheimer's disease (AD) is highly heterogeneous and driven by diverse molecular and cellular mechanisms. Functional genomics investigates these mechanisms from genetic variants to gene expression and regulation. We performed personalized functional genomics analysis on population-scale single-nucleus RNA-seq data, with cross-cohort validation across multiple cohorts comprising over 1900 individual brains, capturing donor-level cell type interactions and gene regulatory networks. Using a...
Efficient differential expression analysis of large-scale single-cell transcriptomics data using Dreamlet
Advances in single-cell and -nucleus transcriptomics have enabled generation of increasingly large-scale datasets from hundreds of subjects and millions of cells. These studies promise to give unprecedented insight into the cell type specific biology of human disease. Yet performing differential expression analyses across subjects remains difficult due to challenges in statistical modeling of these complex studies and scaling analyses to large datasets. Our open-source R package dreamlet (...
Single-cell atlas of transcriptomic vulnerability across brain disorders
Neurodegenerative and neuropsychiatric diseases impose a considerable societal and public health burden. However, our understanding of the molecular mechanisms underlying these highly complex conditions remains limited^(1,2). Here, to gain deeper insights into the aetiology of different brain diseases, we used specimens from 1,494 unique donors to generate a population-scale single-cell transcriptomic atlas of the human dorsolateral prefrontal cortex, comprising over 6.3 million individual...
Single-nucleus atlas of cell-type specific genetic regulation in the human brain
Genetic risk variants for common diseases are predominantly located in non-coding regulatory regions and modulate gene expression. Although bulk tissue studies have elucidated shared mechanisms of regulatory and disease-associated genetics, the cellular specificity of these mechanisms remains largely unexplored. Here we present a comprehensive, single-nucleus multi-ancestry atlas of genetic regulation of gene expression in the human prefrontal cortex, comprising 5.6 million nuclei from 1,384...
Landmark map of human brain's gene activity holds clues to Alzheimer's disease and more
No abstract
AI-based characterization of Alzheimer's disease phenotypes from population-scale single-cell data
The complexity of Alzheimer's disease (AD) manifests in diverse clinical phenotypes, including cognitive impairment and neuropsychiatric symptoms. However, the etiology of these phenotypes remains elusive. To address this, the PsychAD project generated a population-level single-nucleus RNA sequencing dataset comprising over 6 million nuclei from the prefrontal cortex of >1,000 individual brains, covering a variety of disease phenotypes. Here, leveraging this dataset, we developed a computational...
Lsp2 links early-life diet to adult translation and lifespan in Drosophila
Nearly a century ago, restricting diet during early-life periods was suggested to extend lifespan in rats and in Daphnia^(1,2). The effect of juvenile diet on adult physiology and lifespan has subsequently been described in other model organisms, including fruit flies^(3-5) and mice^(6-8); however, its mechanism remains poorly understood. Here, using Drosophila as a model, we show that restricting protein intake during the larval stage (early-life protein restriction; ePR) promotes adult...
Lsp2 links mTORC1 to TOP mRNA translation and lifespan in Drosophila
Mechanistic target of rapamycin complex 1 (mTORC1) senses nutrient availability to orchestrate metabolic processes that are crucial for physiological homeostasis and ageing¹. mTORC1 preferentially regulates the translation of 5'-terminal oligopyrimidine (TOP) motif-containing mRNAs (which encode mainly ribosomal proteins) through the 4E-BP translational repressor²; however, this function of mTORC1 is resistant to rapamycin inhibition³. TOP mRNAs are exceptionally abundant, and thus impose a...
Vascular aging as a driver of organ dysfunction and systemic aging
Centuries ago, Thomas Sydenham famously wrote, "A man is as old as his arteries", highlighting the importance of the vasculature for health and healthy aging. Here, we review recent developments in vascular aging research, focusing on how microvascular aging drives tissue dysfunction and the emerging therapeutic opportunities for vascular rejuvenation. Although macrovascular aging has long been studied, microvascular aging remains an emerging frontier. Recent single-cell and multiomic...
Fast, flexible analysis of differences in cellular composition with crumblr
Changes in cell type composition play an important role in human health and disease. Recent advances in single-cell technology have enabled the measurement of cell type composition at increasing cell lineage resolution across large cohorts of individuals. Yet this raises new challenges for statistical analysis of these compositional data to identify changes in cell type frequency. We introduce crumblr ( DiseaseNeurogenomics.github.io/crumblr ), a scalable statistical method for analyzing count...
Longitudinal digital phenotyping of activity rhythms and biological aging using commercial wearables
Disrupted rest-activity rhythms have been associated with aging and chronic disease, yet longitudinal evidence from free-living populations has been lacking. Here we integrate multi-year Fitbit activity data from the All of Us Research Program with clinical biomarker-derived PhenoAge from 2,222 participants (8,447 person-years). Through high-dimensional digital phenotyping, we show that circadian rest-activity rhythm intensity, timing, and stability are associated with biological aging...
Lifespan single-cell transcriptomic atlas of the human prefrontal cortex
The human brain undergoes profound changes from early development through late adulthood, shaping cognition, behaviour and vulnerability to disease^(1,2). Understanding how these changes are organized within specific brain regions and cell types is essential for interpreting normal ageing and its relationship to psychiatric and neurodegenerative disorders. The dorsolateral prefrontal cortex has a central role in higher cognitive functions and is particularly sensitive to age-related decline³,...
Single-cell atlas of transcriptomic vulnerability across brain disorders
Neurodegenerative and neuropsychiatric diseases impose a considerable societal and public health burden. However, our understanding of the molecular mechanisms underlying these highly complex conditions remains limited^(1,2). Here, to gain deeper insights into the aetiology of different brain diseases, we used specimens from 1,494 unique donors to generate a population-scale single-cell transcriptomic atlas of the human dorsolateral prefrontal cortex, comprising over 6.3 million individual...