Nonlinear DNA methylation trajectories in aging male mice

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Апрель 9, 2024

Abstract Although DNA methylation data yields highly accurate age predictors, little is known about the dynamics of this quintessential epigenomic biomarker during lifespan. To narrow gap, we investigate trajectories male mouse colon at five different time points aging. Our study indicates existence sudden hypermethylation events specific stages life. Precisely, identify two switches early-to-midlife (3-9 months) and mid-to-late-life (15-24 transitions, separating rodents’ life into three stages. These nonlinear predominantly affect genes associated with nervous system enrich in bivalently marked chromatin regions. Based on groups nonlinearly modified loci, construct a clock-like classifier STageR (STage aging estimatoR) that accurately predicts murine epigenetic stage. We demonstrate universality our clock an independent cohort publicly available datasets.

Язык: Английский

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The Role of Gut Microbiota in Neurodegenerative Diseases: Current Insights and Therapeutic Implications

Cureus, Год журнала: 2023, Номер unknown

Опубликована: Окт. 28, 2023

Small microscopic entities known as microbes, having a population of hundreds billions or perhaps even in trillions, reside our gastrointestinal tract. A healthy immune system, digestion, and creation vitamins enzymes are all thanks to these microbes. However, new research has shown hitherto unrecognized connection between the microbiota intestines genesis neurodegenerative diseases. Neurons CNS gradually deteriorate illnesses like multiple sclerosis Parkinson's disease (PD). This deterioration impairs cognitive physical function. Amyotrophic lateral (ALS), PD, Alzheimer's (AD) just few examples that pose serious threat world health have effective treatments. Recent suggests gut microbiota, diverse microbial found may substantially impact cause development various The discovery altered composition people with is one most critical lines evidence connecting dysbiosis AD patients distinct characteristic particular profile. In addition, an excess specific microbe data profile seen compared individual. Similar changes been noted PD. latest study indicates potential dysbiosis, condition characterized by alteration intestinal microbiota's makeup functioning, effect on onset progression diseases, including PD sclerosis. order emphasize any underlying mechanisms examine treatment repercussions, review article's goal summarize current knowledge about disorders. article aims disorders, highlighting examining repercussions.

Язык: Английский

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Autism in patients with eosinophilic gastrointestinal disease: A systematic review with meta‐analysis

Pediatric Allergy and Immunology, Год журнала: 2024, Номер 35(4)

Опубликована: Апрель 1, 2024

Abstract Purpose Neurodevelopmental disorders, such as autism spectrum disorder (ASD), have been increasingly associated with eosinophilic gastrointestinal disorders (EGID). However, the relationship between these diseases remains unclear. We performed a systematic review meta‐analysis to address this issue. Methods The search was according PRISMA guidelines using descriptors for ASD and EGIDs from MEDLINE, Embase, PsycInfo, LILACS, Web of Science databases. Observational studies prevalence in any EGID were included. study protocol registered on PROSPERO platform under number CRD42023455177. Results total dataset comprised 766,082 participants. result single‐arm showed an overall population 21.59% (95% CI: 10.73–38.67). There association (OR: 3.44; 95% 1.25–2.21), also significant when restricted only EoE 3.70; 2.71–5.70). Discussion Recent implicated influence inadequate epithelial barrier integrity pathogenesis several diseases. role mechanism can be extended situations beyond allergic reactions, including other conditions underlying immunological mechanisms. Several are potentially related systemic effect bacterial translocation tissues defective barriers. Conclusion Our provides evidence that supports consideration patients EGID. Despite its limitations, results should validated by future studies, preferably multicenter prospective designs populations low referral bias.

Язык: Английский

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Alzheimer's disease and gut-brain axis: Drosophila melanogaster as a model

Frontiers in Neuroscience, Год журнала: 2025, Номер 19

Опубликована: Фев. 4, 2025

Research indicates that by 2050, more than 150 million people will be living with Alzheimer's disease (AD), a condition associated neurodegeneration due to the accumulation of amyloid-beta and tau proteins. In addition genetic background, endocrine disruption, cellular senescence, management gut microbiota has emerged as key element in diagnosis, progression, treatment AD, certain bacterial metabolites can travel through bloodstream cross blood-brain barrier. This mini-review explores relationship between protein dysbiosis Drosophila melanogaster . model facilitates investigation how gut-derived contribute neurocognitive impairment dementia. Understanding role direct indirect by-products, such lactate acetate, glial cell activation dynamics may provide insights into mechanisms AD progression effective treatments. Here we discuss simplicity extensive tools make it valuable for studying these interactions testing potential therapeutics, including probiotics. Integrating studies other established models reveal conserved pathways accelerate translation findings clinical applications.

Язык: Английский

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Potential of Akkermansia muciniphila and its outer membrane proteins as therapeutic targets for neuropsychological diseases

Frontiers in Microbiology, Год журнала: 2023, Номер 14

Опубликована: Июнь 27, 2023

The gut microbiota varies dramatically among individuals, and changes over time within the same individual, due to diversities in genetic backgrounds, diet, nutrient supplementations use of antibiotics. Up until now, studies on dysbiosis have expanded a wider range diseases, with Akkermansia muciniphila at cross spot many these diseases. A. is Gram-negative bacterium that produces short-chain fatty acids (SCFAs), Amuc_1100 one its most highly expressed outer membrane proteins. This review aims summarize current knowledge correlations between involved neuropsychological diseases published last decade, focus potential this proteins as therapeutic targets for basis evidence accumulated from animal clinical studies, well mechanisms action peripheral central nervous system (CNS).

Язык: Английский

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Correlation between Alzheimer’s Disease and Gastrointestinal Tract Disorders

Nutrients, Год журнала: 2024, Номер 16(14), С. 2366 - 2366

Опубликована: Июль 21, 2024

Alzheimer’s disease is the most common cause of dementia globally. The pathogenesis multifactorial and includes deposition amyloid-β in central nervous system, presence intraneuronal neurofibrillary tangles a decreased amount synapses. It remains uncertain what causes progression disease. Nowadays, it suggested that brain connected to gastrointestinal tract, especially enteric system gut microbiome. Studies have found positive association between AD diseases such as periodontitis, Helicobacter pylori infection, inflammatory bowel microbiome disorders. H. its metabolites can enter CNS via oropharyngeal olfactory pathway may predispose onset AD. Periodontitis systemic inflammation low severity with high levels pro-inflammatory cytokines neutrophils. Moreover, lipopolysaccharide from oral bacteria accompanies beta-amyloid plaques form brain. Increased intestinal permeability IBS leads neuronal transference. Chronic lead plaque formation tract spreads vagus nerve. plays an important role many bodily functions, nutrient absorption vitamin production, but also factor development diseases, including Both quantity diversity change significantly patients even people preclinical stage disease, when symptoms are not yet present. influences functioning through, among other things, microbiota–gut–brain axis. Given involvement AD, antibiotic therapy, probiotics prebiotics, faecal transplantation being considered possible therapeutic options.

Язык: Английский

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On the Response of Proteinoid Ensembles to Fibonacci Sequences

ACS Omega, Год журнала: 2025, Номер 10(10), С. 10401 - 10424

Опубликована: Март 5, 2025

This work investigates the integration of Fibonacci patterns and Golden Ratio principles into proteinoid-based systems, connecting fundamental mathematical concepts with contemporary biomimetic approaches. Proteinoids are thermal proteins that can self-assemble have enzyme-like capabilities. They provide a distinct platform for information processing. Our study examines impact integrating sequences (ϕ = 1.618) design synthesis proteinoids on their structural organization response characteristics. We developed two categories stimuli: auditory signals generated using frequencies derived from sequence, electrical correspond to proportions Ratio. The proteinoid microsphere assemblies were subjected these stimuli, responses recorded analyzed. results indicate systems reveal unique reactivity acoustic stimuli based exhibiting heightened sensitivity particular combinations demonstrating nonlinear amplification effects. exhibited distinctive temporal dynamics emergent oscillatory behaviors when exposed voltage inspired by Ratio, which not detected ordinary input signals. These findings opportunities developing advanced bioinspired transfer security might improve our understanding processing in early chemical systems.

Язык: Английский

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Microbiome Alterations and Alzheimer’s Disease: Modeling Strategies with Transgenic Mice

Biomedicines, Год журнала: 2023, Номер 11(7), С. 1846 - 1846

Опубликована: Июнь 27, 2023

In the last decade, role of microbiota–gut–brain axis has been gaining momentum in context many neurodegenerative and metabolic disorders, including Alzheimer’s disease (AD) diabetes, respectively. Notably, a balanced gut microbiota contributes to epithelial intestinal barrier maintenance, modulates host immune system, releases neurotransmitters and/or neuroprotective short-chain fatty acids. However, dysbiosis may provoke dysregulation, impacting neuroinflammation through peripheral–central communication. Moreover, lipopolysaccharide or detrimental microbial end-products can cross blood–brain induce at least potentiate neuropathological progression AD. Thus, after repeated failure find cure for this dementia, necessary paradigmatic shift towards considering AD as systemic disorder occurred. Here, we present an overview use germ-free transgenic animal models valid tools unravel connection between dysbiosis, diseases, AD, investigate novel therapeutical targets. Given high impact dietary habits, not only on but also other well-established risk factors such diabetes obesity, consistent changes lifestyle along with microbiome-based therapies should be considered complementary approaches.

Язык: Английский

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Mitochondria of intestinal epithelial cells in depression: Are they at a crossroads of gut-brain communication?

Neuroscience & Biobehavioral Reviews, Год журнала: 2023, Номер 153, С. 105403 - 105403

Опубликована: Сен. 23, 2023

The role of gut dysbiosis in depression is well established. However, recent studies have shown that microbiota regulated by intestinal epithelial cell (IEC) mitochondria, which has yet to receive much attention. This review summarizes the developments about critical IEC mitochondria actively maintaining microbiota, metabolism, and immune homeostasis. We propose mitochondrial dysfunction alters composition, participates fate, mediates oxidative stress, activates peripheral system, causes inflammation, transmits signals through vagus enteric nervous systems. These pathological alterations lead brain disruption blood-brain barrier, activation hypothalamic-pituitary-adrenal axis, microglia astrocytes, induction neuronal loss, ultimately depression. Furthermore, we highlight prospect treating IECs. new findings suggest IECs may be a newly found important factor pathogenesis represent potential strategy for

Язык: Английский

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ADAR-mediated regulation of PQM-1 expression in neurons impacts gene expression throughout C. elegans and regulates survival from hypoxia

PLoS Biology, Год журнала: 2023, Номер 21(9), С. e3002150 - e3002150

Опубликована: Сен. 25, 2023

The ability to alter gene expression programs in response changes environmental conditions is central the of an organism thrive. For most organisms, nervous system serves as master regulator communicating information about animal's surroundings other tissues. relay centers on signaling pathways that cue transcription factors a given cell type execute specific program, but also provide means signal between factor PQM-1 important mediator insulin pathway contributing longevity and stress well impacting survival from hypoxia. Herein, we reveal novel mechanism for regulating specifically neural cells larval animals. Our studies RNA-binding protein (RBP), ADR-1, binds pqm-1 mRNA cells. This binding regulated by presence second RBP, ADR-2, which when absent leads reduced both downstream activated genes. Interestingly, find sufficient impact throughout animal affect hypoxia, phenotypes observe adr mutant Together, these posttranscriptional regulatory Caenorhabditis elegans allows sense respond promote organismal

Язык: Английский

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