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Investigating age-associated changes in intestine and understanding immune-related intestinal dysfunctions is essential for promoting healthy ageing. Mucosal surfaces represent a distinct immune compartment enriched with specialised lymphocytes that interact dynamically with the epithelial layer. In this study, we present novel spatially resolved insights into the cellular and molecular alterations in the ageing murine gut mucosa. Our findings reveal a complex network of interdependent...

T cell output from the thymus falls throughout life and is associated with profound remodeling of the thymic stroma. To what extent the decline in T cell output is caused by aging of the hematopoietic stem and progenitor cells (HSPCs) has been difficult to define because of HSPC heterogeneity, the multi-stage process of HSPC migration, and the cross-talk between hematopoietic and stromal elements of the thymus. To address the contribution of HSPC aging on T cell development, we interrogated T...

CONCLUSION: These findings identify oxidative stress and disrupted autophagy as key mediators of saturated-fat-induced neuronal decline and highlight a sex-specific vulnerability to dietary fat composition. This work establishes Drosophila as a powerful model for dissecting nutritional drivers of neural aging and suggests that metabolic stress pathways represent critical early targets in diet-associated neurodegeneration.

CONCLUSIONS: Personal EHR engagement among the vulnerable aging population is influenced by a complex interplay of patient, HCP, and technology-related factors, which must be addressed holistically to ensure inclusive usage and adherence to digital health tools.

A common brain protein may be giving Alzheimer’s disease an unexpected way to spread, carrying toxic Tau proteins from damaged neurons into healthy ones. By blocking these harmful protein packages before they reach new cells, researchers believe it may one day be possible to slow the disease's relentless progression.

Creatine is best known as a muscle-building supplement, but scientists are now investigating whether it could also help treat depression by boosting the brain's energy supply. A new review examined five randomized clinical trials involving 238 participants and found mixed results. Two studies, both involving women with major depressive disorder, reported that adding creatine to standard treatment improved symptoms, while three others found no meaningful benefit.

A new stem-cell-inspired technique allows scientists to grow vast numbers of immune-cell progenitors that can be engineered to hunt cancer and strengthen immune responses. In animal studies, the cells fought tumors, restored immune function, and showed promise as a durable, off-the-shelf therapy platform.

Researchers tested experimental PCAI compounds against pancreatic cancer cells and found they had powerful anticancer effects. One leading compound blocked more than 90% of cancer cell migration, suggesting it could help prevent the spread of tumors. Rather than suppressing cancer signaling, the treatment hyperactivated key pathways until the cells essentially self-destructed.

Science, Ahead of Print.

Tau pathology spreads cell to cell, but the mechanisms of intercellular tau transmission remain unclear. We find that the neuronal gene Arc is critical for the release of tau in neuronal extracellular vesicles (EVs) via a direct protein-protein interaction. Brain EVs purified from transgenic rTg4510 mutant tau mice (rTg^(WT)) crossed with Arc knockout mice (rTg^(Arc KO)) contain less tau and reduced tau seeding potential. Both Arc and tau are co-packaged in mouse and human brain-derived EVs....

Tau is an intrinsically disordered protein that functions to support cytoskeletal stability by binding microtubules in neuronal axons. While tau is involved in healthy neuronal function, it can become pathogenic by forming protein aggregates leading to neurologic diseases collectively known as tauopathies, which include Alzheimer's disease, frontotemporal dementia, and chronic traumatic encephalopathy. Post-translational modifications, including phosphorylation, O-GlcNAcylation, acetylation,...

Neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and others, are a group of neurological disorders characterized by progressive neuronal loss in the central nervous system (CNS) and the deterioration of CNS function. Multiple lines of evidence have highlighted activation of innate immune cells in the CNS, namely microglia and astrocytes, as hallmark pathological features in neurodegeneration and key drivers of disease progression....

Astrocytes, long considered supportive cells of the central nervous system (CNS), have critical roles in innate immunity. This Review explores immune signaling pathways in astrocytes, including pattern recognition through Toll-like receptors, nucleic acid sensors and inflammasomes. These pathways enable the detection of danger signals and initiate protective responses and endogenous innate immune functions. Downstream signaling pathways, including the interferon, NF-κB and STAT3 pathways,...

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