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Galaxy clusters obey the inverse square law across hundreds of millions of light-years

Neurons and glia are distinct in their morphology, development and function, possessing unique transcriptomes and proteomes, but little is known about their metabolomes. The challenge of brain cell metabolic profiling is to obtain a large number of cells for reliable analysis. Here we purified microglia, astrocytes and neurons from mouse brains, identifying >70 metabolites through targeted metabolomics and 9,854 metabolite features via untargeted metabolomics. We systematically characterized...

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Alzheimer's disease (AD) is characterized by progressive cognitive decline, with synaptic dysfunction as the strongest correlate of clinical symptoms. The apolipoprotein E ε4 (ApoE4) allele is the most potent genetic risk factor for late-onset AD. Beyond its roles in amyloid-β aggregation and tau hyperphosphorylation, ApoE4 disrupts synaptic integrity by perturbing lipid metabolism, neuroimmune regulation, mitochondrial dynamics, and activity-dependent plasticity. These ApoE4-driven mechanisms...

Mitochondrial dysfunction is widely implicated in human disease, yet whether it plays a causal role and why effects are tissue-specific remain unclear. Here, we analyse over 15,000 RNA-sequencing datasets from 49 tissue types integrated with germline genetic data to investigate the impact of mitochondrial DNA (mtDNA) transcription on disease risk. We identify 25 nuclear genetic variants associated with mtDNA transcript abundance, revealing gene- and tissue-specific regulatory architectures. We...

Previous research on the genetic links between cognition and psychopathology has largely treated cognitive function as unitary, in part due to a lack of well-powered genome-wide association studies on specific cognitive domains, particularly crystallized knowledge (also known as crystallized intelligence). Here, we parse the genetics of cognitive test performance into components representing reaction time, fluid reasoning, and crystallized knowledge. This multivariate approach allows us to...

Plants have served as important sources of medicine since prehistoric times, forging a strong connection between humans and their environment. This relationship has yielded valuable insights into the therapeutic use of herbs for various health conditions. The current study aims to gather scientific evidence about traditional Indian anti-aging herbal beverages that have been practiced for centuries. We conducted a literature search through online databases, research articles, search engines, and...

Neurons and glia are distinct in their morphology, development and function, possessing unique transcriptomes and proteomes, but little is known about their metabolomes. The challenge of brain cell metabolic profiling is to obtain a large number of cells for reliable analysis. Here we purified microglia, astrocytes and neurons from mouse brains, identifying >70 metabolites through targeted metabolomics and 9,854 metabolite features via untargeted metabolomics. We systematically characterized...

Senescent cells accumulate with age and contribute to tissue dysfunction and chronic inflammation. Senolytic agents that selectively eliminate senescent cells hold therapeutic promise; however, few mechanistic classes have been established. Using Cell Painting-based morphological profiling, we identified a distinct cluster of senolytic compounds comprised of both known and novel autophagy inhibitors, including AZ191, bafilomycin A1, chloroquine, daurisoline, dauricine, MCOPPB, and its derivative...

Protein epigenetic scores (EpiScores) are DNA methylation (DNAm)-based proxies for circulating protein levels and may provide insights into inflammation-cognition relationships. Although some EpiScores have been linked to cognitive decline, it remains unclear whether these proxies show similar associations in other cohorts, and whether their effects vary across distinct cognitive domains. We aimed to evaluate the associations between inflammatory proteins EpiScores and cognitive functions...

Chemotherapy-related cognitive impairment is increasingly recognized as a long-term consequence of cancer treatment, yet the contribution of the cerebrovascular system remains poorly defined. In this study, we investigated the long-term effects of clinically relevant treatment regimens with cyclophosphamide (CP) and vincristine (VIN) on cerebrovascular cellular senescence, associated molecular signatures, and downstream functional outcomes, including disruption of blood-brain barrier (BBB)...

The ovary is one of the first organs to lose functionality with age. We found that aging of the Drosophila ovary is characterized by an accumulation of phenotypes in the somatic compartment, including failure of the follicle cells to encapsulate germ-cell cysts, an extended S phase, and increased DNA damage. In aged ovaries, follicle encapsulation defects are associated with the lack of a germ-cell cyst checkpoint in early oogenesis. Single-cell RNA sequencing revealed that, across all cell...

A blood biomarker reveals the mechanistic shift from amyloid to tau pathology.