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Scientists tested 39 sweeteners and found unexpected gut effects
A large laboratory study found that many commonly used sweeteners can directly change the growth of gut bacteria. Researchers identified more than 100 cases in which sweeteners behaved differently when combined with medications, caffeine, or flavorings. The combination of isosteviol and the antidepressant duloxetine was especially disruptive, reducing beneficial bacteria and overall microbial diversity.
New Alzheimer's drug repairs DNA damage and reduces brain inflammation
A drug originally developed for spinal cord injury may offer a fresh approach to treating Alzheimer’s disease. In mouse studies, KCL-286 repaired dangerous DNA damage, reduced inflammation, and targeted multiple disease-related pathways instead of focusing on just amyloid or tau. Since it has already cleared an initial human safety trial, researchers believe it could move more quickly into Alzheimer’s clinical testing.
This sugar-coated therapy boosted survival against deadly brain cancer by 50% in mice
A new experimental treatment may have found a way to outsmart glioblastoma’s toughest defense: the blood-brain barrier. Researchers used sugar-coated nanoparticles to ferry genetic instructions that restore a key tumor-suppressing protein directly into brain cancer cells. In mouse studies, the therapy increased median survival by 50% while shrinking tumors without noticeable damage to other organs.
This drug could help millions keep their kidneys working longer
An international study found that finerenone slows kidney function decline and reduces the risk of serious kidney and cardiovascular complications in people with chronic kidney disease who do not have diabetes. The results could open the door to a much-needed new treatment option for the majority of CKD patients who have long had limited choices.
Oldest known Mars rock offers glimpse of planet’s watery youth
Ancient Teghaza meteorite hints at granitelike crust and shows Mars was already losing its water 4.1 billion years ago
Bacteria clusters can eject ‘escape pods’ to survive
Finding points to potential way to break apart dangerous biofilms without antibiotics
Climate scientists sharpen tools for linking global warming to extreme weather
National Academies report says the fast-growing field can boost confidence with more rigorous results
Heterogenous microglial reactivity contrasts with stable vascular transcriptional programs in mouse models of Alzheimer's, CADASIL, and Traumatic Brain Injury
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...
Network-based discovery of regulatory drivers of cognitive decline in alzheimer's disease
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...
Developmental priming of adult proteostasis and longevity by NuA4 complex activity in early life
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...
Vitamin C attenuates primate bone marrow aging at the molecular and progenitor level
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...
Functional matrix vesicle replacement partially restores chemo-mechanical coupling in the aged bone niche
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),...
Clonal haematopoiesis of indeterminate potential and epigenetic age acceleration: Systematic review and meta-analysis
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...
Adherence to the Eatwell Guide and associations with markers of physical function: a prospective analysis within the UK Biobank cohort
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...
Developmental priming of adult proteostasis and longevity by NuA4 complex activity in early life
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...
Trained immunity links hematopoietic stem cell aging to aging-associated inflammation
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...
Mesenchymal Stem Cell-Derived Exosomes Improve Aging-Related Changes in Liver Lipid Metabolism by Enhancing Autophagy
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...
Hiding in plain sight: uncovering the genetic basis of complex phenotypes through low-risk groups
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...
Spatiotemporally homogeneous crystallization for ambient scalable perovskite photovoltaics
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...
Restored clearance of senescent neutrophils by tissue-resident macrophages limits organ aging
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...