The Continuum of Aging and Age-Related Diseases: Common Mechanisms but Different Rates

Frontiers in Medicine, Год журнала: 2018, Номер 5

Опубликована: Март 12, 2018

Geroscience, the new interdisciplinary field that aims to understand relationship between aging and chronic age-related diseases (ARDs) geriatric syndromes (GSs), is based on epidemiological evidence experimental data major risk factor for such pathologies assumes ARDs/GSs share a common set of basic biological mechanisms. A consequence primary target medicine combat instead any single ARD/GSs one by one, as favored fragmentation into hundreds specialties sub-specialties. If same molecular cellular mechanisms underpin both ARDs/GSs, question emerges: which difference, if any, ARDs/GSs? The hypothesis ARDs GSs frailty can be conceptualized accelerated will discussed analyzing in particular frailty, sarcopenia, obstructive pulmonary disease, cancer, neurodegenerative Alzheimer Parkinson well Down syndrome an example progeroid syndrome. According this integrated view, become part continuum where precise boundaries do not exist two extremes are represented centenarians, who largely avoided or postponed most characterized decelerated aging, patients suffered more severe their 60s, 70s, 80s show signs respectively. In these extremes, there intermediate trajectories representing sort gray area. Thus, clinically different, classical are, indeed, result peculiar combinations alterations regarding same, limited shared with process. Whether individual follow trajectory depend his/her genetic background interacting lifelong environmental lifestyle factors. manifestations it urgent identify markers capable distinguishing chronological age subjects at higher developing GSs. To aim, we propose use DNA methylation, N-glycans profiling, gut microbiota composition complement available disease-specific markers.

Язык: Английский

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Brain-Gut-Microbiota Axis in Alzheimer’s Disease

Journal of Neurogastroenterology and Motility, Год журнала: 2019, Номер 25(1), С. 48 - 60

Опубликована: Янв. 10, 2019

Disturbances along the brain-gut-microbiota axis may significantly contribute to pathogenesis of neurodegenerative disorders. Alzheimer's disease (AD) is most frequent cause dementia characterized by a progressive decline in cognitive function associated with formation amyloid beta (Aβ) plaques and neurofibrillary tangles. Alterations gut microbiota composition induce increased permeability barrier immune activation leading systemic inflammation, which turn impair blood-brain promote neuroinflammation, neural injury, ultimately neurodegeneration. Recently, Aβ has also been recognized as an antimicrobial peptide participating innate response. However, dysregulated state, reveal harmful properties. Importantly, bacterial amyloids through molecular mimicry elicit cross-seeding misfolding microglial priming. The seeding propagation occur at different levels axis. potential mechanisms spreading include neuron-to-neuron or distal neuron spreading, direct crossing via other cells astrocytes, fibroblasts, microglia, system cells. A growing body experimental clinical data confirms key role dysbiosis microbiota-host interactions convergence gut-derived inflammatory response together aging poor diet elderly AD. Modification food-based therapy probiotic supplementation create new preventive therapeutic options

Язык: Английский

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Impact of microbiota on central nervous system and neurological diseases: the gut-brain axis

Journal of Neuroinflammation, Год журнала: 2019, Номер 16(1)

Опубликована: Март 1, 2019

Development of central nervous system (CNS) is regulated by both intrinsic and peripheral signals. Previous studies have suggested that environmental factors affect neurological activities under physiological pathological conditions. Although there anatomical separation, emerging evidence has indicated the existence bidirectional interaction between gut microbiota, i.e., (diverse microorganisms colonizing human intestine), brain. The cross-talk microbiota brain may crucial impact during basic neurogenerative processes, in neurodegenerative disorders tumors CNS. In this review, we discuss biological interplay gut-brain axis, further explore how communication be dysregulated diseases. Further, highlight new insights modification composition, which emerge as a promising therapeutic approach to treat CNS disorders.

Язык: Английский

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The Gut-Brain Axis: How Microbiota and Host Inflammasome Influence Brain Physiology and Pathology

Frontiers in Immunology, Год журнала: 2020, Номер 11

Опубликована: Дек. 10, 2020

The human microbiota has a fundamental role in host physiology and pathology. Gut microbial alteration, also known as dysbiosis, is condition associated not only with gastrointestinal disorders but diseases affecting other distal organs. Recently it became evident that the intestinal bacteria can affect central nervous system (CNS) inflammation. tract are communicating through bidirectional network of signaling pathways called gut-brain axis, which consists multiple connections, including vagus nerve, immune system, bacterial metabolites products. During these dysregulated altered permeability blood-brain barrier (BBB) neuroinflammation. However, numerous mechanisms behind impact gut neuro-development -pathogenesis remain poorly understood. There several involved CNS homeostasis Among those, inflammasome pathway been linked to neuroinflammatory conditions such sclerosis, Alzheimer’s Parkinson’s diseases, anxiety depressive-like disorders. complex assembles upon cell activation due exposure microbes, danger signals, or stress lead production pro-inflammatory cytokines (interleukin-1β interleukin-18) pyroptosis. Evidences suggest there reciprocal influence brain. how this precisely working yet be discovered. Herein, we discuss status knowledge open questions field focusing on function products cells during healthy inflammatory conditions, neuropsychiatric In particular, focus innate mechanism certain microbes.

Язык: Английский

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Mechanisms and consequences of intestinal dysbiosis

Cellular and Molecular Life Sciences, Год журнала: 2017, Номер 74(16), С. 2959 - 2977

Опубликована: Март 28, 2017

Язык: Английский

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Altered bile acid profile associates with cognitive impairment in Alzheimer's disease—An emerging role for gut microbiome

Alzheimer s & Dementia, Год журнала: 2018, Номер 15(1), С. 76 - 92

Опубликована: Окт. 15, 2018

Abstract Introduction Increasing evidence suggests a role for the gut microbiome in central nervous system disorders and specific gut‐brain axis neurodegeneration. Bile acids (BAs), products of cholesterol metabolism clearance, are produced liver further metabolized by bacteria. They have major regulatory signaling functions seem dysregulated Alzheimer's disease (AD). Methods Serum levels 15 primary secondary BAs their conjugated forms were measured 1464 subjects including 370 cognitively normal older adults, 284 with early mild cognitive impairment, 505 late 305 AD cases enrolled Neuroimaging Initiative. We assessed associations BA profiles selected ratios diagnosis, cognition, AD‐related genetic variants, adjusting confounders multiple testing. Results In compared to we observed significantly lower serum concentrations (cholic acid [CA]) increased bacterially produced, BA, deoxycholic acid, its glycine taurine forms. An ratio acid:CA, which reflects 7α‐dehydroxylation CA bacteria, strongly associated decline, finding replicated brain samples Rush Religious Orders Memory Aging Project. Several variants immune response–related genes implicated showed profiles. Discussion report first time an association between altered profile, AD, changes using large multicenter study. These findings warrant investigation dysbiosis possible gut‐liver‐brain pathogenesis AD.

Язык: Английский

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Age‐related changes in the gut microbiota influence systemic inflammation and stroke outcome

Annals of Neurology, Год журнала: 2018, Номер 84(1), С. 23 - 36

Опубликована: Май 7, 2018

Chronic systemic inflammation contributes to the pathogenesis of many age-related diseases. Although not well understood, alterations in gut microbiota, or dysbiosis, may be responsible for inflammation.Using stroke as a disease model, we tested hypothesis that youthful when established aged mice, produces positive outcomes following ischemic stroke. Conversely, an young negative after Young and male mice had either microbiota by fecal transplant gavage (FTG). Mice were subjected (middle cerebral artery occlusion; MCAO) sham surgery. During subsequent weeks, underwent behavioral testing samples collected 16S ribosomal RNA analysis bacterial content.We found is altered experimental resembles biome uninjured mice. In ratio Firmicutes Bacteroidetes (F:B), two main phyla increased ∼9-fold (p < 0.001) compared young. This F:B indicative dysbiosis. Altering resemble (∼6-fold increase ratio, p mortality MCAO, decreased performance testing, cytokine levels. altering (∼9-fold decrease survival improved recovery MCAO.Aged levels proinflammatory cytokines. We conclude can modified positively impact from Ann Neurol 2018;83:23-36.

Язык: Английский

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The progress of gut microbiome research related to brain disorders

Journal of Neuroinflammation, Год журнала: 2020, Номер 17(1)

Опубликована: Янв. 17, 2020

Abstract There is increasing evidence showing that the dynamic changes in gut microbiota can alter brain physiology and behavior. Cognition was originally thought to be regulated only by central nervous system. However, it now becoming clear many non-nervous system factors, including gut-resident bacteria of gastrointestinal tract, regulate influence cognitive dysfunction as well process neurodegeneration cerebrovascular diseases. Extrinsic intrinsic factors dietary habits composition microbiota. Microbes release metabolites microbiota-derived molecules further trigger host-derived cytokines inflammation system, which contribute greatly pathogenesis host disorders such pain, depression, anxiety, autism, Alzheimer’s diseases, Parkinson’s disease, stroke. Change blood–brain barrier permeability, vascular physiology, structure are among most critical causes development downstream neurological dysfunction. In this review, we will discuss following parts: Overview technical approaches used microbiome studies Microbiota immunity Gut Microbiota-induced Neuropsychiatric diseases ■ Stress depression Pain migraine Autism spectrum Neurodegenerative disease Amyotrophic lateral sclerosis Multiple Cerebrovascular Atherosclerosis Stroke Arteriovenous malformation Conclusions perspectives

Язык: Английский

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Secretory Products of the Human GI Tract Microbiome and Their Potential Impact on Alzheimer's Disease (AD): Detection of Lipopolysaccharide (LPS) in AD Hippocampus

Frontiers in Cellular and Infection Microbiology, Год журнала: 2017, Номер 7

Опубликована: Июль 11, 2017

Although the potential contribution of human gastrointestinal (GI) tract microbiome to health, aging and disease is becoming increasingly acknowledged, molecular mechanics signaling pathways just how this accomplished not well understood. Major bacterial species GI tract, such as abundant Gram-negative bacilli Bacteroides fragilis (B. fragilis) Escherichia coli (E. coli), secrete a remarkably complex array pro-inflammatory neurotoxins which, when released from confines healthy are pathogenic highly detrimental homeostatic function neurons in central nervous system (CNS). For first time here we report presence lipopolysaccharide (LPS) brain lysates hippocampus superior temporal lobe neocortex Alzheimer's (AD) brains. Mean LPS levels varied 2-fold increases 3-fold hippocampus, AD over age-matched controls, however some samples advanced hippocampal cases exhibited up 26-fold increase controls. This 'Perspectives' paper will further highlight very recent research on CNS, update current findings that implicate microbiome-derived an important internal contributor inflammatory degeneration CNS.

Язык: Английский

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Alzheimer’s Disease Microbiome Is Associated with Dysregulation of the Anti-Inflammatory P-Glycoprotein Pathway

mBio, Год журнала: 2019, Номер 10(3)

Опубликована: Май 6, 2019

Studies of the intestinal microbiome and AD have demonstrated associations with composition at genus level among matched cohorts. We move this body literature forward by more deeply investigating via metagenomics comparing patients against those without dementia other types. also exploit machine learning approaches that combine both metagenomic clinical data. Finally, our functional studies using stool samples from elders demonstrate how c can affect health dysregulation P-glycoprotein pathway. contributes directly to inflammatory disorders intestine. Since has been long thought be linked chronic bacterial infections as a possible etiology, findings therefore fill gap in knowledge field research identifying nexus between microbiome, loss homeostasis, inflammation may underlie neurodegenerative disorder.

Язык: Английский

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