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Hundreds of grants axed in a field where the United States was a global leader

Tau accumulation is closely related to cognitive symptoms in Alzheimer's disease (AD). However, the cellular drivers of tau-dependent decline of memory-based cognition remain elusive. Here, we employed in vivo Neuropixels and patch-clamp recordings in mouse models and demonstrate that tau, independent of β-amyloid, selectively debilitates complex-spike burst firing of CA1 hippocampal neurons, a fundamental cellular mechanism underpinning learning and memory. Impaired bursting was associated with...

Epigenomic profiling of the brain has largely been done on bulk tissues, limiting our understanding of cell type-specific epigenetic changes in disease states. Here, we introduce cell type-specific histone acetylation score (CHAS), a computational tool for inferring cell type-specific signatures in bulk brain H3K27ac profiles. We applied CHAS to >300 H3K27ac chromatin immunoprecipitation sequencing samples from studies of Alzheimer's disease, Parkinson's disease, autism spectrum disorder,...

Quantification of the absolute microbial abundance in a human stool sample is crucial for a comprehensive understanding of the microbial ecosystem, but this information is lost upon metagenomic sequencing. While several methods exist to measure absolute microbial abundance, they are technically challenging and costly, presenting an opportunity for machine learning. Here, we observe a strong correlation between DNA concentration and the absolute number of 16S ribosomal RNA copies as measured by...

Lipids metabolism is crucial in regulating aging and metabolic diseases. Lipid droplets (LDs) are dynamic, complex organelles responsible for the storage and release of neutral lipids, essential for maintaining lipid homeostasis and energy metabolism. Aging accelerates the accumulation of LDs, functional deterioration, and metabolic disorders, thereby inducing age-related metabolic diseases (ARMDs). This review examines published datasets on the association between LDs and ARMDs, focusing on the...

Antibodies that recognize insoluble antigens, such as amyloid fibrils associated with neurodegenerative disorders, are important for research, diagnostic and therapeutic applications. However, these types of antibodies are difficult to generate, typically require animal immunization and also commonly require humanization in the case of therapeutic applications. Here we report a methodology for generating high-quality, fully human, conformation-specific antibodies against amyloid fibrils using a...

Human-rodent chimeric brain models serve as a unique platform for investigating the pathophysiology of human cells within a living brain environment. These models are established by transplanting human tissue- or human pluripotent stem cell (hPSC)-derived macroglial, microglial, or neuronal lineage cells, as well as cerebral organoids, into the brains of host animals. This approach has opened new avenues for exploring human brain development, disease mechanisms, and regenerative processes. Here,...

Lipids metabolism is crucial in regulating aging and metabolic diseases. Lipid droplets (LDs) are dynamic, complex organelles responsible for the storage and release of neutral lipids, essential for maintaining lipid homeostasis and energy metabolism. Aging accelerates the accumulation of LDs, functional deterioration, and metabolic disorders, thereby inducing age-related metabolic diseases (ARMDs). This review examines published datasets on the association between LDs and ARMDs, focusing on the...

CONCLUSION: Extreme weather events significantly impact malnutrition and food security among older adults, with outcomes influenced by socio-economic and geographical factors. Further longitudinal studies are needed to clarify causal pathways and inform targeted public health interventions to enhance resilience in aging populations.

Aging is characterized by extensive variability in the onset of morbidity and mortality, even in genetically identical populations with carefully controlled environments. This points to the important role stochasticity plays in shaping the divergent aging process between individual organisms. Here, we survey how stochastic factors at the level of molecules, cells, tissues, and organisms manifest in and impact the aging process, with a focus on the nematode Caenorhabditis elegans. Findings of...

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Exploring the genomic basis of transcriptional programs has been a long-standing research focus. Here we report a single-cell method, ChAIR, to map chromatin accessibility, chromatin interactions and RNA expression simultaneously. After validating in cultured cells, we applied ChAIR to whole mouse brains and delineated the concerted dynamics of epigenome, three-dimensional (3D) genome and transcriptome during maturation and aging. In particular, gene-centric chromatin interactions and open...

Transposable elements (TEs) are mobile repetitive nucleic acid sequences that have been incorporated into the genome through spontaneous integration, accounting for almost 50% of human DNA. Even though most TEs are no longer mobile today, studies have demonstrated that they have important roles in different biological processes, such as ageing, embryonic development, and cancer. TEs influence these processes through various mechanisms, including active transposition of TEs contributing to...

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Elucidating the regulatory mechanisms of human cardiac aging remains a great challenge. Here, using human heart tissues from 74 individuals ranging from young (≤35 years) to old (≥65 years), we provide an overview of the histological, cellular and molecular alterations underpinning the aging of human hearts. We decoded aging-related gene expression changes at single-cell resolution and identified increased inflammation as the key event, driven by upregulation of ARID5A, an RNA-binding protein....

Theta-gamma transcranial alternating current stimulation (TG tACS) over primary motor cortex (M1) can improve ballistic motor performance in young adults, but the effect on older adults is unknown. This study investigated the effects of TG tACS on motor performance and M1 excitability in 18 young and 18 older adults. High-definition TG tACS (6 Hz theta, 75 Hz gamma) or sham tACS was applied over right M1 for 20 min during a ballistic left-thumb abduction motor training task performed in two...

During aging, microglia - the resident macrophages of the brain - exhibit altered phenotypes and contribute to age-related neuroinflammation. While numerous hallmarks of age-related microglia have been elucidated, the progression from homeostasis to dysfunction during the aging process remains unresolved. To bridge this gap in knowledge, we undertook complementary cellular and molecular analyses of microglia in the mouse hippocampus across the adult lifespan and in the experimental aging model...

Higher cardiorespiratory fitness (CRF) is associated with less deterioration in brain microstructural white matter (WM) integrity in older adults assessed with MRI diffusion tensor imaging (DTI) and brain WM hyperintensities (WMH) volume measured with fluid-attenuated-inversion-recovery (FLAIR) imaging. This study investigated associations of CRF measured with peak oxygen consumption (V̇O(2peak)) with brain WM microstructural integrity and WMH in healthy individuals across the adult lifespan. We...

Biological age (BA), compared to chronological age, offers a more accurate reflection of aging status. In this prospective UK Biobank study, BA acceleration was measured using the Klemera-Doubal method BA (KDM-BA) and Phenotypic age (PhenoAge). Cox models estimated associations of BA acceleration with incident T2D (n = 271,885) and CAD (n = 270,054). Both additive and multiplicative interactions between BA acceleration and polygenic risk score (PRS) were examined. Predictive performance was...

This optical illusion from the natural world is testing the limits of computer vision