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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.

P. F. Giannopoulos, J. Chiu, and D. Praticò, "Antileukotriene Therapy by Reducing Tau Phosphorylation Improves Synaptic Integrity and Cognition of P301S Transgenic Mice," Aging Cell 17, no. 3 (2018): e12759, https://doi.org/10.1111/acel.12759. The above article, published online on 01 April 2018 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Monty Montano; The Anatomical Society; and John Wiley & Sons Ltd. The retraction has...

Myocardial infarction (MI) is the leading cause of cardiovascular-related deaths worldwide, with risk increasing sharply with age. Fibrosis and inflammation occur soon after a pathological event and reflect perturbation of tissue repair that accompanies aging in general. Yet not old, but young animals are typically used for studying MI, emphasizing the unmet need for more relevant preclinical models. We previously determined that plasma dilution, also termed neutral blood exchange (NBE)...

Environmental antibiotic pollution is an underexplored contributor to gut aging and chronic intestinal diseases. We provide evidence that chronic exposure to enrofloxacin (ENR), a commonly detected veterinary antibiotic, accelerates gut aging and disease progression through a mitochondria-centered mechanism. In a population-based cross-sectional analysis, recent antibiotic use was associated with increased biological age and a higher risk of diarrhea in middle-aged and older adults, supporting a...

All organisms employ strategies to cope with changing environmental conditions. In budding yeast, nutrient deprivation induces a reversible non-proliferative state known as quiescence, characterized by extensive remodeling of gene expression, metabolism, and cellular biophysical properties. Yeast cells survive prolonged periods of starvation-induced quiescence, provided they can respire in the early stages of glucose withdrawal, and blocking respiration causes premature aging and markedly...

CONCLUSION: This study demonstrates that specific gut microbial profiles are significantly associated with sarcopenia. Akkermansia and Lactobacillus were associated with sarcopenia, although greater Roseburia levels were beneficial. These microbial signatures are associated with sarcopenia and warrant further longitudinal investigation.

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