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AI-generated scientific hypotheses lag human ones when put to the test
Machines still face hurdles in identifying fresh research paths, study suggests
Age-associated trajectories of hippocampus subregion volumes from childhood through later adulthood
The hippocampus has been widely implicated in the neurobiology of neurologic and psychiatric disorders. This structure is heterogeneous, however, and comprised of multiple subregions that have different connectivity patterns and functions. Better understanding how these subregions are affected by age and their relationship with neurocognition could provide information regarding how alterations in normal trajectories play a role in disease and cognitive dysfunction. Using natural splines we...
Personalized cognitive enhancement for older adults: An aging-friendly closed-loop human-machine interface framework
Emerging digitally delivered non-pharmacological interventions (dNPIs) offer scalable, low-risk solutions for enhancing cognitive function in older adults, yet their effectiveness remains inconsistent due to a lack of personalization and precise mechanisms of action. Generic, population-based designs often fail to predict individual gains, underscoring the need for more tailored approaches. To address this, we propose a closed-loop human-machine interface (HMI) framework for personalizing dNPIs...
KDM4 Orchestrates Epigenomic Remodeling of Senescent Cells and Potentiates the Senescence-Associated Secretory Phenotype
Cellular senescence restrains the expansion of neoplastic cells through several layers of regulation. We report that the histone H3-specific demethylase KDM4 is expressed as human stromal cells undergo senescence. In clinical oncology, upregulated KDM4 and diminished H3K9/H3K36 methylation correlate with poorer survival of patients with prostate cancer after chemotherapy. Global chromatin accessibility mapping via assay for transposase-accessible chromatin with high-throughput sequencing, and...
Age-dependent effect of environmental enrichment on the neural 3D chromatin interactome
Aging is a multifactorial biological process resulting in physiological and cellular decline. However, our understanding of age-related changes in 3D genome organization and the effect of external interventions on this process remains limited. Here, we describe alterations in the landscape of the 3D chromatin interactome upon aging, utilizing the low-input promoter capture Hi-C (liCHi-C) technique with mouse hippocampal neurons. We also integrated liCHi-C data with RNA sequencing (RNA-seq) data...
Aging and liver health: liver chemistries and associated factors in community-dwelling older adults
CONCLUSIONS: Liver chemistries in community-dwelling older adults with normal nutritional status were within the normal reference range used for adults. There were small but statistically significant differences with age, sex, and intensity of statin therapy. ALT declined with age, and further prospective studies are required to determine cut-offs for increased risk of adverse clinical outcomes.
Lysosomal polyamine storage upon ATP13A2 loss impairs β-glucocerebrosidase via altered lysosomal pH and electrostatic hydrolase-lipid interactions
ATP13A2 is an endolysosomal polyamine transporter mutated in several neurodegenerative conditions involving lysosomal defects, including Parkinson's disease (PD). While polyamines are polybasic and polycationic molecules that play pleiotropic cellular roles, their specific impact on lysosomal health is unknown. Here, we demonstrate lysosomal polyamine accumulation in ATP13A2 knockout (KO) cell lines and human induced pluripotent stem cell (iPSC)-derived neurons. Primary polyamine storage caused...
Cobalt-based catalyst for ammonia synthesis under ambient conditions via transient confinement
The Haber-Bosch process is used for industrial ammonia production worldwide, and it accounts for ~2% of the global energy consumption and 1.3% anthropogenic carbon footprint. Ammonia synthesis under ambient conditions with minimum carbon emission is highly desired, but it is still in the initial stage. Herein, we report a cobalt-based catalyst for ammonia continuous synthesis under ambient conditions via mechanochemistry. To describe mechanochemistry of ammonia synthesis, density functional...
Successful aging and its associated factors among older adults in Nepal: a cross-sectional study
CONCLUSION: As increasing age was associated with lower odds of successful aging, older adults could be encouraged to maintain partnerships, engage in some form of employment or volunteer activities, and participate in physical activity to promote successful aging.
Association between age and malnutrition in oldest-old and centenarian populations
CONCLUSIONS: This study demonstrated a linear association between age and malnutrition in Chinese oldest-old populations and indicated interaction effects of cigarette smoking, red meat consumption, and vegetable consumption on malnutrition. Food consumption is related to nutritional status as a key element in age-malnutrition association. An in-depth understanding of food and nutrition in older adults could help establish evidence-based recommendations to increase survival rate.
Jingfang granule extends lifespan and healthspan in Caenorhabditis elegans: insights from RNA-seq analysis of genetic mechanisms
Traditional Chinese Medicine (TCM), as a globally recognized phytomedicinal approach, has made significant contributions to healthcare and anti-aging research worldwide. Jingfang Granule (JFG), an established TCM preparation in China, was demonstrated to exert effects on prolonging lifespan and healthspan via the Caenorhabditis elegans model in this study. We employed RNA-seq analysis to investigate the complex genetic interactions through which JFG extends the lifespan of C. elegans. We...
Role of branched chain amino acid metabolism on aging
Aging is a complex biochemical phenomenon that considerably impacts both individual health and societal dynamics. Recent researches have emphasized the essential function of metabolism in the processes of aging and longevity. Metabolites-chemical byproducts produced by the host organism and its symbiotic partners, including the microbiota, are generated through numerous metabolic pathways. In the last fifteen years, major progress has been made in elucidating the metabolism of BCAAs and the...
Plasma tau biomarkers for biological staging of Alzheimer's disease
A blood biomarker-based staging system for Alzheimer's disease (AD) could improve the diagnosis, prognosis and identification of individuals most likely to benefit from specific therapies. Here, using targeted mass spectrometry, we measured six phosphorylated and six nonphosphorylated tau peptides in plasma from two independent cohorts: BioFINDER-2 and TRIAD (n = 689). We also analyzed the ratios of phosphorylated to nonphosphorylated peptides. Our results revealed that specific tau species...
Ageing well in the urban environment: meeting the health and social needs of older Adults - study protocol for a prospective, longitudinal mixed-methods study
BACKGROUND: Urbanisation and ageing populations are global challenges for ageing well. This mixed-methods study examines the health and social needs of older adults in urban areas in Berlin, Germany and in Singapore, focusing on three key dimensions of healthy ageing and wellbeing: health, mobility, loneliness, and equity as a cross-cutting theme.
Supreme Court upholds Trump cancellation of NIH grants
Justices rule lower court had no authority to compel restoration of more than 800 studies on diversity, transgender health, and other sensitive topics
Understanding monocyte-driven neuroinflammation in Alzheimer's disease using human cortical organoid microphysiological systems
Increasing evidence strongly links neuroinflammation to Alzheimer's disease (AD) pathogenesis. Peripheral monocytes are crucial components of the human immune system, but their contribution to AD pathogenesis is still largely understudied partially due to limited human models. Here, we introduce human cortical organoid microphysiological systems (hCO-MPSs) to study AD monocyte-mediated neuroinflammation. By culturing doughnut-shape organoids on 3D-printed devices within standard 96-well plates,...
Quantum Dots in Neurotheranostics for the Treatment of Alzheimer's Disease
Age-related neurodegeneration is one of the primary causes associated with the pathogenesis of Alzheimer's disease (AD). Currently, there are 5.8 million cases of AD worldwide. With the advancement in technology, the paradigm of treating the disease has shifted from one treatment or diagnosis to simultaneously diagnosing as well as treating the disease. Excellent efforts have been made by the scientists towards the development of nanotheranostics. Among them, quantum dots (QDs) have shown...
Interactions with tau's microtubule-binding repeats modulate amyloid-β aggregation and toxicity
The complicated pathogenesis of Alzheimer's disease (AD) is characterized by the accumulation of neurofibrillary tangles and senile plaques, primarily composed of tau and amyloid-β (Aβ) aggregates, respectively. While substantial efforts have focused on unraveling the individual roles of tau and Aβ in AD development, the intricate interplay between these components remains elusive. Here we report how the microtubule-binding repeats of tau engage with Aβ in a distinct manner. Crucially, this...
Unraveling lymphoma-induced immune senescence
B cell lymphomas arise from mutations that disrupt normal germinal center B cell programs and promote a microenvironment that fosters aberrant proliferation and immune escape. In this issue of Cancer Cell, Hesterberg et al. show that lymphoma accelerates T cell aging by transcriptional and epigenetic reprogramming that mirrors physiological aging.
Lymphoma accelerates T cell and tissue aging
The combined effects of aging and cancer on immune cells were investigated in young versus aged mice harboring B cell lymphoma, and in T cells from young and aged B cell lymphoma patients. These analyses revealed that lymphoma alone is sufficient to trigger transcriptional, epigenetic, and phenotypic alterations in young T cells that manifest in aged T cells. In contrast, aged T cells are largely resistant to lymphoma-induced changes. Pathway analyses revealed open chromatin regions and genes...