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Heterogenous microglial reactivity contrasts with stable vascular transcriptional programs in mouse models of Alzheimer's, CADASIL, and Traumatic Brain Injury

1 day ago
The extent to which the cerebrovasculature is affected in various brain disorders is still not well understood. To address this, we established a transcriptomic repository of major vascular cell types and microglia to compare the global transcriptomic response in mouse models of three human brain disorders linked to neuroinflammation and associated vascular reactivity: Alzheimer's disease (AD), traumatic brain injury (TBI), and cerebral autosomal dominant arteriopathy with subcortical infarcts...
K D Bjørnholm

Network-based discovery of regulatory drivers of cognitive decline in alzheimer's disease

1 day ago
Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder marked by progressive cognitive decline, yet its transcriptional regulatory architecture remains poorly understood. Here, we model sample-specific gene regulatory networks (GRNs) from dorsolateral prefrontal cortex transcriptomes of 87 individuals with AD and 67 non-cognitively impaired (NCI) controls and use a machine learning classifier to detect consistent disease-specific network features. This sample-specific network...
Danish Anwer

Developmental priming of adult proteostasis and longevity by NuA4 complex activity in early life

1 day ago
Proteostasis collapse, a hallmark of aging and neurodegeneration like Alzheimer's disease (AD), causes irreversible damage in late life. Whether late-life proteostasis capacity is developmentally programmed remains unclear, as mechanistic studies requiring lifelong tracking and molecular manipulation are challenging or impossible in long-lived species. Using C. elegans as a lifelong, genetically tractable AD model, we uncover a critical early-life window during which reducing TIP60/NuA4...
Yihan Wang

Vitamin C attenuates primate bone marrow aging at the molecular and progenitor level

1 day ago
Bone marrow aging compromises hematopoiesis and immunity, yet whether these processes are modifiable in primates remains unexplored. Here, we map the single-cell transcriptomic landscape of primate bone marrow aging and demonstrate that long-term oral vitamin C (VC) supplementation attenuates selected molecular and progenitor-level decline. Aging drives severe common lymphoid progenitor (CLP) depletion, myeloid-biased hematopoietic stem and progenitor cell (HSPC) output, and anatomical...
Yanxia Ye

Functional matrix vesicle replacement partially restores chemo-mechanical coupling in the aged bone niche

1 day ago
Skeletal aging involves pyrophosphate/phosphate disequilibrium and impaired mechanotransduction, which together constrain osteogenic repair. We develop OsteoVes, a matrix-vesicle-mimetic extracellular organelle that combines tissue-nonspecific alkaline phosphatase (ALP)-mediated inorganic pyrophosphate (PPi) hydrolysis, nano-hydroxyapatite nucleation, and a mesenchymal stem cell-derived membrane interface for extracellular matrix anchoring. In aged human mesenchymal stem/stromal cells (MSCs),...
Liqiang Zhang

Clonal haematopoiesis of indeterminate potential and epigenetic age acceleration: Systematic review and meta-analysis

1 day ago
Clonal haematopoiesis of indeterminate potential (CHIP) represents somatic mutations in haematopoietic stem cells that drive clonal expansion. Epigenetic age acceleration (EAA), estimated from DNA methylation (DNAm) clocks, may capture age-related changes in haematopoiesis. This systematic review and meta-analysis was conducted to synthesise evidence on associations between CHIP and EAA and explore shared biological mechanisms that may underlie this relationship. Six databases were searched from...
Matthew W Simonson

Adherence to the Eatwell Guide and associations with markers of physical function: a prospective analysis within the UK Biobank cohort

1 day ago
The Eatwell Guide represents the UK's principal healthy eating model and understanding whether adherence to UK dietary recommendations can attenuate age-related functional decline is essential to inform healthy ageing strategies. In up to 157,457 participants from the UK Biobank, we explored cross-sectional and prospective associations between adherence to the Eatwell Guide and markers of physical function (grip strength, fat-free mass percentage, self-reported walking pace, and falls). Eatwell...
Alex Griffiths

Developmental priming of adult proteostasis and longevity by NuA4 complex activity in early life

1 day ago
Proteostasis collapse, a hallmark of aging and neurodegeneration like Alzheimer's disease (AD), causes irreversible damage in late life. Whether late-life proteostasis capacity is developmentally programmed remains unclear, as mechanistic studies requiring lifelong tracking and molecular manipulation are challenging or impossible in long-lived species. Using C. elegans as a lifelong, genetically tractable AD model, we uncover a critical early-life window during which reducing TIP60/NuA4...
Yihan Wang

Trained immunity links hematopoietic stem cell aging to aging-associated inflammation

1 day ago
Trained immunity is a state of heightened immune response that is initiated in hematopoietic stem cells (HSCs) and mediated mainly by their myeloid progeny. Aging-associated inflammation drives many aging-related diseases, yet its biological origin is largely unknown. Here we show that SIRT3, a mitochondrial deacetylase highly expressed in HSCs but reduced during aging, suppresses the HSC response to aging that drives maladaptive trained immunity, chronic inflammation and tissue functional...
Wei-Chieh Mu

Mesenchymal Stem Cell-Derived Exosomes Improve Aging-Related Changes in Liver Lipid Metabolism by Enhancing Autophagy

1 day ago
Health problems associated with aging have become increasingly severe in recent years. For example, hepatic lipid metabolism declines as the body ages, leading to lipid metabolic disorders. Although exosomes have been explored for treating metabolic diseases, there is currently a paucity of research regarding aging-related changes in hepatic lipid metabolism. Herein, we cultured human umbilical cord mesenchymal stem cells (HucMSCs), from which we extracted HucMSC-derived exosomes (HucMDEs). We...
Jinquan Li

Hiding in plain sight: uncovering the genetic basis of complex phenotypes through low-risk groups

1 day ago
Medical genetic studies focus on high-risk groups to enrich for targeted phenotypes. Although genetic effects may vary across the lifespan, age-related enrichment of target phenotypes can also arise from cumulative environmental exposures, without requiring changes in genetic architecture. Accumulating environmental effects over the lifetime can inflate nongenetic variance, creating the illusion of greater genetic signal while in fact masking underlying genetic effects. We propose investigating...
Ana I Vazquez

Spatiotemporally homogeneous crystallization for ambient scalable perovskite photovoltaics

1 day ago
Commercializing perovskite solar cells (PSCs) will likely require the scalable deposition of homogeneous perovskite films under ambient conditions. However, the spatially heterogeneous degradation of metastable perovskites during prolonged coating leads to nonuniformity. Here, we demonstrate spatiotemporally homogeneous crystallization of α-phase FAPbI(3) (where FA is formamidinium) enabled by a phase-locking strategy that establishes a dynamically evolving, moisture-buffering intergranular...
Binlou Gao

Restored clearance of senescent neutrophils by tissue-resident macrophages limits organ aging

1 day ago
Aging disrupts tissue homeostasis across organ systems. Here, we identify tissue-resident macrophages (TRMs) as central coordinators of age-related organ decline through impaired clearance of senescent neutrophils, a process regulated by the immunomodulatory prostaglandin E2 (PGE(2)) receptor EP2. Reducing TRM EP2 signaling in aged mice preserved youthful mitochondrial fitness and prevented cognitive decline, frailty, sarcopenia, adiposity, cardiac impairment, and systemic inflammation. Plasma...
Yuting Jessy Tan

Choose Home: Veteran and Caregiver Perspectives on the Acceptability of a Novel Short-Term Home Care Program

1 day ago
CONCLUSIONS: Choose Home was highly acceptable to Veterans and caregivers, who perceived improvements in health, self-management, and caregiving self-efficacy. By filling a gap between acute and longitudinal services, Choose Home may strengthen efforts to deliver whole-person, home-based care. Continued implementation and rigorous evaluation are warranted to assess long-term outcomes and scalability within VA and beyond.
Rebecca J Howe

Circular RNAs-Stress Granule Interplay Drives Aging-Related Proteostasis Loss

1 day ago
Aging involves a gradual loss of cellular balance, leading to reduced function and increased disease risk. While impaired proteostasis is a key hallmark of aging, more evidence shows the importance of RNA homeostasis (ribostasis), particularly the regulation of circular RNAs (circRNAs). CircRNAs are stable RNA molecules that build up over time and are linked to age-related cellular dysfunctions. In this regard, Kim et al. 2026 provide new insights into the impact of circRNA turnover on aging and...
José M Izquierdo

Regulatory T cell immunosuppressive function requires chaperone-mediated autophagy

1 day ago
Regulatory T cells (Tregs) are essential for maintaining immune tolerance. We recently identified chaperone-mediated autophagy (CMA), a selective lysosomal degradation pathway, as a critical regulator of Treg function. Treg activation induces CMA, but this response is markedly diminished with aging. Mice lacking CMA specifically in Tregs develop systemic inflammation, impaired immune tolerance and reduced lifespan. We confirm that CMA is a fundamental mechanism supporting Treg suppressive...
Ranee Harrison