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Microglial capacity to adapt to tissue needs is a hallmark feature of these cells. New studies show that mitochondria critically regulate the phenotypic adaptability of macrophages. To determine whether these organelles play similar roles in shaping microglial phenotypes, we generated transgenic mouse crosses to accurately visualize and manipulate microglial mitochondria. We find that brain-region differences in microglial attributes and responses to aging are accompanied by regional differences...

The EAT-Lancet diet has been recently recommended for its potential health and environmental benefits. Here, leveraging data from the UK Biobank, we performed a comparative analysis to examine the associations of adherence to the EAT-Lancet diet versus traditional plant-based diets with biological aging and further assess the mediating role of metabolomic signatures specific to dietary patterns. Compared with the overall or healthful plant-based diet index, higher adherence to the EAT-Lancet...

Liver-expressed antimicrobial peptide-2 (LEAP-2), the endogenous antagonist of the ghrelin receptor (GHSR1a), counterbalances ghrelin in an energy- and inflammation-dependent manner. Aging is accompanied by endocrine and immunometabolic shifts that may influence this axis. We investigated whether a short course of broad-spectrum antibiotics (vancomycin-metronidazole-neomycin-ampicillin; VMNA) alters LEAP-2 and ghrelin levels in the liver and epididymal white adipose tissue (WAT) of aged male...

CONCLUSION: The present findings emphasize that strengthening individual resilience, along with promoting social and family support and paying attention to emotional relationships, is effective in reducing loneliness in older people.

Growing evidence shows that epigenetic modification and mitochondrial dysfunction are hallmarks of aging and are associated with the development of a wide range of age-related diseases. Mitochondrial biogenesis, which is marked by mitochondrial DNA copy number (mtDNAcn), is one of the major regulations of mitochondrial function by a set of transacting elements, including mitochondrial DNA polymerase gamma (POLG), working on the mtDNA control region. In this study, we investigated the mtDNAcn and...

How do neurophysiological traits that characterize individuals evolve across the lifespan? To address this question, we analyzed task-free magnetoencephalographic recordings from over 1,000 individuals aged 4-89. We found that neurophysiological activity is more similar between individuals in childhood than in adulthood, an effect driven predominantly by arrhythmic brain activity. In contrast, periodic activity-based profiles remain reliable markers of individuality across all ages. The cortical...

INTRODUCTION: Primitive reflexes (PRs) are brainstem-mediated automatic responses that typically disappear in early life, but may reappear in older age, which may be associated with neurodegenerative processes. But the presence of PRs in cognitively healthy adults has not yet been sufficiently explored. The relationship between PRs and cognitive functioning (COG) may be influenced by modifiable factors such as physical activity (PA) and psychological resilience. This cross-sectional...

Policy to be implemented next year drew more than 900 comments, most of them critical

FURIN cleaves a subset of proproteins into functional mature fragments. Evidence suggests that FURIN is involved in brain development and the associated diseases, whereas the potential mechanisms remain incompletely understood. Here, we report that cerebral FURIN-deficient mice exhibit cognitive decline and neurodegeneration. Lipid droplets (LDs) that are preferentially accumulated in astrocytes correlate with an increase of the LD markers PLIN2 and PLIN3, and conversely a decreased level of...

Parkinson's disease (PD) is a neurodegenerative disease that manifests motor and non-motor symptoms due to the progressive loss of dopaminergic neurons in the substantia nigra. While its pathogenesis is multifactorial, with genetic as well as environmental components, more and more evidence suggests that nutrition and diet play an important role in regulating both the development and progression of the disease through crosstalk with genetics, a term known as nutrigenomics. This review discusses...

Cellular senescence contributes to age-related neurodegeneration, yet its manifestation varies across brain cell types and senescence-inducing stressors. Here, we investigated senescence hallmarks in five human brain cell lines - astrocytes, endothelial cells, microglia, oligodendrocytes, and dopaminergic-like neurons - using chronic 5-Bromodeoxyuridine treatment and validated our findings in primary cells and alternative toxin-induced models. Principal component analysis and transcriptional...

Transcriptome- and proteome-wide association studies (TWAS/PWAS) have proven successful in prioritizing genes and proteins whose genetically regulated expression modulates disease risk, but they ignore potential co-expression and interaction effects. To address this limitation, we introduce the co-expression-wide association study (COWAS) method, which can identify pairs of genes or proteins whose genetically regulated co-expression is associated with complex traits. COWAS first trains models to...