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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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Age-related declines in motor learning are commonly attributed to changes in sensorimotor neurophysiology. However, direct links between neurochemistry, electrophysiology, and behavior are scarce. Here, we investigated whether age-related differences in GABAergic inhibition and cortical reactivity mediate age-related simple and complex motor learning declines. To do so, we employed magnetic resonance spectroscopy (MRS) and transcranial magnetic stimulation-electroencephalography (TMS-EEG) in...

CONCLUSIONS: Low DOBS and accelerated PhenoAge were jointly associated with a higher likelihood of CMM among U.S. older adults, highlighting the potential relevance of dietary oxidative balance and biological aging in cardiometabolic multimorbidity.

Frailty, a clinical syndrome of multisystem decline and homeostatic vulnerability, is a critical public health priority. While the gut microbiome regulates immune and metabolic signaling, current evidence remains fragmented. We performed a metagenomic meta-analysis of 955 individuals from 28 independent cohorts across 24 countries to identify universal microbial signatures and develop a generalizable discriminative model. Frailty was determined using a Proxy Frailty Index based on the deficit...

CONCLUSION: High-intensity aerobic exercise increased serum zonulin more than low-intensity exercise in older adults, suggesting differential effects on intestinal barrier-related responses. Although inflammatory markers tended to improve more with high-intensity exercise, these findings should be interpreted cautiously. Individualized exercise prescription may be needed when considering effects on intestinal barrier function in older adults.

CONCLUSION: Our integrative study demonstrates that aging-induced SPARCL1 deficiency in brain endothelial cells causally contributes to VaD pathogenesis. These findings highlight SPARCL1 as a mechanistically grounded and therapeutically promising target for VaD.

Telomere-driven replicative crisis transforms the architecture of the evolving cancer genome, yet the mechanisms and consequences remain incompletely resolved, with potential biomarkers undiscovered. To address this, we have employed novel tools and methodologies to explore a human fibroblast model of crisis using high resolution multi-omics analyses. We have developed a unique chromatin conformation capture procedure for identifying distant genomic loci that interact with eroding telomeres,...

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ONC201 is a first-in-class, FDA-approved small molecule activator of the mitochondrial ATP-dependent caseinolytic peptidase P (ClpP). This and other related small molecules referred to as ClpP agonists, exert antiproliferative effects in several cancer cell types. We report that ONC201 and highly potent second generation ClpP agonists (TR-57, TR-107), promote induction of senescence in triple-negative breast cancer (TNBC) cell lines. Senescence was determined by increased β-galactosidase (β-gal)...

Over the past decades, numerous studies aimed to discover the fundamental cause of the aging process. Rather than a single root cause, multiple factors were identified, suggesting that aging manifests itself through a progressive degradation of different molecules, cells and in the end, entire systems, directly affecting an individual's health. To address this rapidly growing challenge, various anti-aging strategies have been proposed, among which partial reprogramming has emerged as a promising...

Aging is associated with neuromuscular decline, but how sex modulates motor unit adaptations across adulthood remains unclear. This study examined age- and sex-related differences in motor unit firing behavior in young (YG), middle-aged (MA), and older (OLD) adults by integrating high-density surface EMG decomposition with assessments of muscle morphology and daily physical activity. Linear mixed-effects models revealed significant effects of age and sex on mean firing rate: females showed...