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Postbiotics as a therapeutic tool in Alzheimer's disease: Insights into molecular pathways and neuroprotective effects

2 months 1 week ago
Alzheimer's disease (AD) is a progressive neurodegenerative disease, characterized by oxidative stress, neuroinflammation, mitochondrial dysfunction, neurotransmitter imbalance, tau hyperphosphorylation, and amyloid beta (Aβ) accumulation in brain regions. The gut microbiota (GM) has a major impact on brain function due to its bidirectional interaction with the gut through the gut-brain axis. The gut dysbiosis has been associated with neurological disorders, emphasizing the importance of gut...
Khadga Raj Aran

Understanding of Alzheimer's disease pathophysiology for therapeutic implications of natural products as neuroprotective agents

2 months 1 week ago
Alzheimer's disease (AD) is a leading cause of dementia, affecting more than 24.3 million people worldwide in 2024. Sporadic AD (SAD) is more common and occurs in the geriatric population, while familial AD (FAD) is rare and appears before the age of 65 years. Due to progressive cholinergic neuronal loss and modulation in the PKC/MAPK pathway, β-secretase gets upregulated, leading to Aβ aggregation, which further activates tau kinases that form neurofibrillary tangles (NFT). Simultaneously,...
Sneh Prabha

Synaptic plasticity and neuroprotection: The molecular impact of flavonoids on neurodegenerative disease progression

2 months 1 week ago
Flavonoids are a broad family of polyphenolic chemicals that are present in a wide variety of fruits, vegetables, and medicinal plants. Because of their neuroprotective qualities, flavonoids have attracted a lot of interest. The potential of flavonoids to control synaptic plasticity-a crucial process underlying memory, learning, and cognitive function-is becoming more and more clear. Dysregulation of synaptic plasticity is a feature of neurodegenerative diseases such as amyotrophic lateral...
Spandana Rajendra Kopalli

Development of a Short Telomere Zebrafish Model for Accelerated Aging Research and Antiaging Drug Screening

2 months 1 week ago
Increased life expectancy is associated with a higher risk of age-related diseases, which represent a major public health challenge. Animal models play a crucial role in aging research, enabling the study of diseases at the organism level and facilitating drug development and repurposing. Among these models, zebrafish stands out as an excellent in vivo system due to its unique characteristics. However, the longevity of zebrafish is a limitation for research, as it often takes too long to obtain...
David Hernández-Silva

Reproductive-Triggered Sterol Competition Exacerbates Age-Related Intestinal Barrier Damage in Drosophila Females

2 months 1 week ago
The trade-off between reproduction and lifespan has been documented across a wide array of organisms, ranging from invertebrates to mammals. In malnourishing dietary conditions, inhibition of the reproductive processes generally extends the lifespan of females. However, the underlying mechanisms through which nutritional competition driven by reproduction accelerates aging remain poorly understood. Here, using female Drosophila melanogaster as a model, we show that among various dietary...
Guixiang Yu

PCSK9 affects vascular senescence through the SIRT1 pathway

2 months 1 week ago
Age is an independent risk factor for atherosclerotic cardiovascular disease that increases the susceptibility of older adults to vascular intimal thickening, endothelial dysfunction, and thrombosis. However, the mechanism underlying vascular injury is not fully understood. In the present study, the effect of proprotein convertase subtilin-type kexin 9 (PCSK9) inhibitors on the senescent state of human umbilical vein endothelial cells (HUVECs) and on senescent mice and lipopolysaccharides (LPS)...
Yuqin Wang

Exenatide once a week versus placebo as a potential disease-modifying treatment for people with Parkinson's disease in the UK: a phase 3, multicentre, double-blind, parallel-group, randomised, placebo-controlled trial

2 months 1 week ago
BACKGROUND: GLP-1 receptor agonists have neurotrophic properties in in-vitro and in-vivo models of Parkinson's disease and results of epidemiological studies and small randomised trials have suggested possible benefits for risk and progression of Parkinson's disease. We aimed to establish whether the GLP-1 receptor agonist, exenatide, could slow the rate of progression of Parkinson's disease.
Nirosen Vijiaratnam

Aspirin inhibits proteasomal degradation and promotes α-synuclein aggregate clearance through K63 ubiquitination

2 months 1 week ago
Aspirin is a potent lysine acetylation inducer, but its impact on lysine ubiquitination and ubiquitination-directed protein degradation is unclear. Herein, we develop the reversed-pulsed-SILAC strategy to systematically profile protein degradome in response to aspirin. By integrating degradome, acetylome, and ubiquitinome analyses, we show that aspirin impairs proteasome activity to inhibit proteasomal degradation, rather than directly suppressing lysine ubiquitination. Interestingly, aspirin...
Jing Gao

Biological age model using explainable automated CT-based cardiometabolic biomarkers for phenotypic prediction of longevity

2 months 1 week ago
We derive and test a CT-based biological age model for predicting longevity, using an automated pipeline of explainable AI algorithms that quantifies skeletal muscle, abdominal fat, aortic calcification, bone density, and solid abdominal organs. We apply these AI tools to abdominal CT scans from 123,281 adults (mean age, 53.6 years; 47% women; median follow-up, 5.3 years). The final weighted CT biomarker selection was based on the index of prediction accuracy. The CT model significantly...
Perry J Pickhardt

A quantitative ultrastructural timeline of nuclear autophagy reveals a role for dynamin-like protein 1 at the nuclear envelope

2 months 1 week ago
Autophagic mechanisms that maintain nuclear envelope homoeostasis are bulwarks to ageing and disease. Here we define a quantitative and ultrastructural timeline of nuclear macroautophagy (nucleophagy) in yeast by leveraging four-dimensional lattice light sheet microscopy and correlative light and electron tomography. Nucleophagy begins with a rapid accumulation of the selective autophagy receptor Atg39 at the nuclear envelope and finishes in ~300 s with Atg39-cargo delivery to the vacuole....
Philip J Mannino

Investigating genetic links between biological aging and adverse pregnancy outcomes

2 months 1 week ago
Observational studies suggest a link between biological aging and adverse pregnancy outcomes (APOs), but causal relationships remain unclear. This study aimed to investigate the relationship between genetically predicted biological aging traits and APOs. Genetic summary statistics from the genome-wide association study (GWAS) of the IEU open GWAS, FinnGen, and meta-analysis were analyzed using Mendelian randomization (MR) to infer causality. Biological aging indicators included facial aging,...
Ning Sun