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Understanding of Alzheimer's disease pathophysiology for therapeutic implications of natural products as neuroprotective agents
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,...
Synaptic plasticity and neuroprotection: The molecular impact of flavonoids on neurodegenerative disease progression
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...
Development of a Short Telomere Zebrafish Model for Accelerated Aging Research and Antiaging Drug Screening
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...
Reproductive-Triggered Sterol Competition Exacerbates Age-Related Intestinal Barrier Damage in Drosophila Females
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...
PCSK9 affects vascular senescence through the SIRT1 pathway
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)...
Congress could soon erase Biden rules on archaeology, climate, and the environment
Seldom used law could enable Republicans to repeal numerous regulations
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
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.
Aspirin inhibits proteasomal degradation and promotes α-synuclein aggregate clearance through K63 ubiquitination
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...
Biological age model using explainable automated CT-based cardiometabolic biomarkers for phenotypic prediction of longevity
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...
A quantitative ultrastructural timeline of nuclear autophagy reveals a role for dynamin-like protein 1 at the nuclear envelope
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....
Investigating genetic links between biological aging and adverse pregnancy outcomes
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,...
The transcription factor STAT3 and aging: an intermediate medium
Aging is a physiological/pathological process accompanied by progressive impairment of cellular function, leading to a variety of aging-related diseases. STAT3 is one of the core regulatory factors of aging. It is involved in body metabolism, development and senescence, cell apoptosis and so on. During the aging process, the changes of growth factors and cytokines will cause the activation of STAT3 to varying degrees, regulate the inflammatory pathways related to aging, regulate body...
Harnessing the fundamental roles of vitamins: the potent anti-oxidants in longevity
Aging is a complex and heterogeneous biological process characterized by telomere attrition, genomic instability, mitochondrial dysfunction, and disruption in nutrient sensing. Besides contributing to the progression of cancer, metabolic disorders, and neurodegenerative diseases, these manifestations of aging also adversely affect organ function. It is crucial to understand these mechanisms and identify interventions to modulate them to promote healthy aging and prevent age-related diseases....
Plasma therapy: a novel intervention to improve age-induced decline in deudenal cell proliferation in female rat model
Aging is associated with a disruptive decline in gastrointestinal health leading to decreased duodenal cell proliferation ultimately affecting the digestive and absorptive capacity of intestines in all species. This study investigates the novel application of blood plasma therapy to enhance duodenal cell proliferation associated with aging. In the presented study, the effects of middle aged plasma therapy on the aged rat duodenum were investigated. For this purpose, using a randomized controlled...
scCamAge: A context-aware prediction engine for cellular age, aging-associated bioactivities, and morphometrics
Current deep-learning-based image-analysis solutions exhibit limitations in holistically capturing spatiotemporal cellular changes, particularly during aging. We present scCamAge, an advanced context-aware multimodal prediction engine that co-leverages image-based cellular spatiotemporal features at single-cell resolution alongside cellular morphometrics and aging-associated bioactivities such as genomic instability, mitochondrial dysfunction, vacuolar dynamics, reactive oxygen species levels,...
Aging restricts the initial neural patterning potential of developing neural stem and progenitor cells in the adult brain
CONCLUSION: Our study demonstrates that patterning potential decreases over time and aging imposes restrictions on preliminary neural patterning. These results emphasize the significance of patterning in the nervous system and the close relationship between patterning and fate determination, raising questions about the application of aged NSPCs in the treatment of neurodegenerative diseases.
Diagnostic potential of urinary CX3CL1 for amnestic mild cognitive impairment and Alzheimer's disease
CONCLUSION: Urinary CX3CL1 levels correlate with the aging process and may serve as a potential diagnostic biomarker for both amnestic mild cognitive impairment (aMCI) and Alzheimer's disease (AD).
NIH slashes overhead payments for research, sparking outrage and lawsuit
Move to cut indirect cost rate to 15% could cost universities billions of dollars