scholarly journals Two phases of aging separated by the Smurf transition as a public path to death

2015 ◽  
Author(s):  
Emilie Dambroise ◽  
Lea Monnier ◽  
Lu Ruisheng ◽  
Hugo Aguilaniu ◽  
Jean-Stephane Joly ◽  
...  
Keyword(s):  
Homo Sapiens ◽  
Intestinal Barrier ◽  
Drosophila Virilis ◽  
Physiological Changes ◽  
Barrier Dysfunction ◽  
Risk Of Death ◽  
Invertebrate Species ◽  
The Past ◽  
Age Dependent ◽  
Two Phases

Aging s most obvious characteristic is the time dependent increase of an individual s probability to die. This lifelong process is accompanied by a large number of molecular and physiological changes. Although numerous genes involved in aging have been identified in the past decades its leading factors have yet to be determined. To identify the very processes driving aging we have developed in the past years an assay to identify physiologically old individuals in a synchronized population of Drosophila melanogaster. Those individuals show an age-dependent increase of intestinal permeability followed by a high risk of death. Here we show that this physiological marker of aging is conserved in 3 invertebrate species Drosophila mojavensis, Drosophila virilis, Caenorhabditis elegans and 1 vertebrate specie Danio rerio. Our findings suggest that intestinal barrier dysfunction may be an important event in the aging process conserved across a broad range of species, thus raising the possibility that it may also be the case in Homo sapiens.

scholarly journals Systemic brain derived neurotrophic factor but not intestinal barrier integrity is associated with cognitive decline and incident Alzheimer’s disease

PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0240342
Author(s):  
Robin M. Voigt ◽  
Shohreh Raeisi ◽  
Jingyun Yang ◽  
Sue Leurgans ◽  
Christopher B. Forsyth ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Pilot Study ◽  
Neurotrophic Factor ◽  
Intestinal Barrier ◽  
Brain Derived Neurotrophic Factor ◽  
Barrier Dysfunction ◽  
Barrier Integrity ◽  
Risk Of Death ◽  
Intestinal Barrier Integrity ◽  
Global Cognition

The inflammatory hypothesis posits that sustained neuroinflammation is sufficient to induce neurodegeneration and the development of Alzheimer’s disease (AD) and Alzheimer’s dementia. One potential source of inflammation is the intestine which harbors pro-inflammatory microorganisms capable of promoting neuroinflammation. Systemic inflammation is robustly associated with neuroinflammation as well as low levels of brain derived neurotrophic factor (BDNF) in the systemic circulation and brain. Thus, in this pilot study, we tested the hypothesis that intestinal barrier dysfunction precedes risk of death, incident AD dementia and MCI, cognitive impairment and neuropathology. Serum BDNF was associated with changes in global cognition, working memory, and perceptual speed but not risk of death, incident AD dementia, incident MCI, or neuropathology. Neither of the markers of intestinal barrier integrity examined, including lipopolysaccharide binding protein (LBP) nor intestinal fatty acid binding protein (IFABP), were associated with risk of death, incident AD dementia, incident mild cognitive impairment (MCI), change in cognition (global or domains), or neuropathology. Taken together, the data in this pilot study suggest that intestinal barrier dysfunction does not precede diagnosis of AD or MCI, changes in cognition, or brain pathology. However, since MCI and AD are related to global cognition, the findings with BDNF and the contiguous cognitive measures suggest low power with the trichotomous cognitive status measures. Future studies with larger sample sizes are necessary to further investigate the results from this pilot study.

Introduction

2018 ◽  
Author(s):  
Gianfranco Pacchioni
Keyword(s):  
Industrial Revolution ◽  
Homo Sapiens ◽  
Modern Society ◽  
Full Time ◽  
Human Race ◽  
Hunter Gatherers ◽  
The Past ◽  
The World ◽  
The Universe ◽  
Radical Transformation

About 10,000 years ago, at the beginning of the agriculturalrevolution, on the whole earth lived between 5 and 8 million hunter-gatherers, all belonging to the Homo sapiens species. Five thousand years later, freed from the primary needs for survival, some belonging to that species enjoyed the privilege of devoting themselves to philosophical speculation and the search for transcendental truths. It was only in the past two hundred years, however, with the advent of the Industrial Revolution, that reaping nature’s secrets and answering fundamental questions posed by the Universe have become for many full-time activities, on the way to becoming a real profession. Today the number of scientists across the globe has reached and exceeded 10 million, that is, more than the whole human race 10,000 years ago. If growth continues at the current rate, in 2050 we will have 35 million people committed full-time to scientific research. With what consequences, it remains to be understood. For almost forty years I myself have been concerned with science in a continuing, direct, and passionate way. Today I perceive, along with many colleagues, especially of my generation, that things are evolving and have changed deeply, in ways unimaginable until a few years ago and, in some respects, not without danger. What has happened in the world of science in recent decades is more than likely a mirror of a similar and equally radical transformation taking place in modern society, particularly with the advent ...

scholarly journals BAFF Blockade Attenuates Inflammatory Responses and Intestinal Barrier Dysfunction in a Murine Endotoxemia Model

2020 ◽  
Vol 11 ◽  
Author(s):  
Runze Quan ◽  
Chaoyue Chen ◽  
Wei Yan ◽  
Ying Zhang ◽  
Xi Zhao ◽  
...  
Keyword(s):  
Barrier Function ◽  
Intestinal Inflammation ◽  
Inflammatory Responses ◽  
Survival Rates ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Barrier Dysfunction ◽  
Protein Levels ◽  
Lps Challenge ◽  
Endotoxemia Model

B cell-activating factor (BAFF) production is increased in septic patients. However, the specific role of BAFF in sepsis remains unknown. This study was designed to investigate the expression and function of BAFF in an experimental endotoxemia model and to identify the potential mechanisms. We established an endotoxemia mouse (6–8 weeks, 20–22 g) model by administering 30 mg/kg lipopolysaccharide (LPS). BAFF levels in the circulating system and organ tissues were measured 4 and 8 h after LPS injection. Survival rates in the endotoxemia mice were monitored for 72 h after BAFF blockade. The effects of BAFF blockade on systemic and local inflammation, organ injuries, and intestinal barrier function were also evaluated 4 h after LPS treatment. BAFF production was systemically and locally elevated after LPS challenge. BAFF blockade improved the survival rate, systemic inflammation, and multi-organ injuries. Moreover, BAFF blockade attenuated both intestinal inflammation and impaired intestinal permeability. BAFF blockade upregulated ZO-1 and occludin protein levels via the NF-κB/MLCK/MLC signaling pathway. These results suggested that BAFF blockade protects against lethal endotoxemia at least partially by alleviating inflammation, multi-organ injuries, and improving intestinal barrier function and provides a novel focus for further research on sepsis and experimental evidence for clinical therapy.

“So Quick Bright Things Come to Confusion”

1987 ◽  
Vol 13 (2-3) ◽  
pp. 169-187
Author(s):  
Alexander Morgan Capron
Keyword(s):  
Homo Sapiens ◽  
Care Delivery ◽  
Well Being ◽  
Workplace Safety ◽  
Selective Abortion ◽  
Self Identity ◽  
The Past ◽  
Adverse Impacts ◽  
The Rich ◽  
Insurance Discrimination

In the past several decades, the problems facing those of us who labor in the vineyards of health policy and ethics have been the problems of success — first medicine's and then, though to a lesser extent, our own. By this I mean that it has been the remarkable fruits of biomedicine, from research to health care delivery, that have produced the rich harvest of ethical, social and legal issues that have drawn our, and society's, attention.In the basic science laboratory, scientists have developed means to splice pieces of DNA together, raising questions from workplace safety to the reengineering of homo sapiens. Of more immediate concern, tests for genetic susceptibility to disease in one's self and one's offspring have been developed, thereby generating questions about employment and insurance discrimination, selective abortion, and adverse impacts on self-identity and well-being.

scholarly journals STAT3 Signalling via the IL-6ST/gp130 Cytokine Receptor Promotes Epithelial Integrity and Intestinal Barrier Function during DSS-Induced Colitis

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 187
Author(s):  
Lokman Pang ◽  
Jennifer Huynh ◽  
Mariah G. Alorro ◽  
Xia Li ◽  
Matthias Ernst ◽  
...  
Keyword(s):  
Barrier Function ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Intestinal Epithelial ◽  
Barrier Dysfunction ◽  
Epithelial Integrity ◽  
Barrier Integrity ◽  
Gp130 Receptor ◽  
Stat3 Signalling

The intestinal epithelium provides a barrier against commensal and pathogenic microorganisms. Barrier dysfunction promotes chronic inflammation, which can drive the pathogenesis of inflammatory bowel disease (IBD) and colorectal cancer (CRC). Although the Signal Transducer and Activator of Transcription-3 (STAT3) is overexpressed in both intestinal epithelial cells and immune cells in IBD patients, the role of the interleukin (IL)-6 family of cytokines through the shared IL-6ST/gp130 receptor and its associated STAT3 signalling in intestinal barrier integrity is unclear. We therefore investigated the role of STAT3 in retaining epithelial barrier integrity using dextran sulfate sodium (DSS)-induced colitis in two genetically modified mouse models, to either reduce STAT1/3 activation in response to IL-6 family cytokines with a truncated gp130∆STAT allele (GP130∆STAT/+), or by inducing short hairpin-mediated knockdown of Stat3 (shStat3). Here, we show that mice with reduced STAT3 activity are highly susceptible to DSS-induced colitis. Mechanistically, the IL-6/gp130/STAT3 signalling cascade orchestrates intestinal barrier function by modulating cytokine secretion and promoting epithelial integrity to maintain a defence against bacteria. Our study also identifies a crucial role of STAT3 in controlling intestinal permeability through tight junction proteins. Thus, therapeutically targeting the IL-6/gp130/STAT3 signalling axis to promote barrier function may serve as a treatment strategy for IBD patients.

Perturbation of gut microbiota plays an important role in micro/nanoplastics-induced gut barrier dysfunction

Nanoscale ◽  
2021 ◽  
Author(s):  
Jiyan Qiao ◽  
Rui Chen ◽  
Mengjie Wang ◽  
Ru Bai ◽  
Xuejing Cui ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Intestinal Barrier ◽  
Barrier Dysfunction ◽  
Gut Barrier ◽  
Bacterial Composition

Exposure to micro/nanoplastics (M/NPLs) deteriorates the intestinal barrier by disturbing the bacterial composition in the gut.

scholarly journals Obeticholic Acid Inhibits Anxiety via Alleviating Gut Microbiota-Mediated Microglia Accumulation in the Brain of High-Fat High-Sugar Diet Mice

Nutrients ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 940
Author(s):  
Li Wu ◽  
Yuqiu Han ◽  
Zhipeng Zheng ◽  
Shuai Zhu ◽  
Jun Chen ◽  
...  
Keyword(s):  
Metabolic Disorders ◽  
Intestinal Barrier ◽  
Behavioral Performance ◽  
High Fat ◽  
Barrier Dysfunction ◽  
Obeticholic Acid ◽  
Promising Agent ◽  
Serum Biochemical ◽  
Lipid Metabolites ◽  
The Brain

Anxiety is one of the complications of metabolic disorders (MDs). Obeticholic acid (OCA), the bile acids (BAs) derivative, is a promising agent for improving MDs in association with gut dysbiosis. Yet, its protective effect on MDs-driven anxiety remains unknown. Here, we assessed the serum biochemical parameters and behavioral performance by open field and Morris water maze tests in HFHS diet-induced MDs mice after OCA intervention for nine and 18 weeks. Moreover, antibiotics intervention for microbial depletion was conducted simultaneously. We found that OCA treatment inhibited the initiation and progression of anxiety in HFHS diet-MDs mice via a microbiota–BAs–brain axis: OCA decreased the neuroinflammatory microglia and IL-1β expression in the hippocampus, reversed intestinal barrier dysfunction and serum proinflammatory LPS to a normal level, modified the microbial community, including the known anxiety-related Rikenellaceae and Alistipes, and improved the microbial metabolites especially the increased BAs in feces and circulation. Moreover, the OCA-reversed bile acid taurocholate linked disordered serum lipid metabolites and indole derivatives to anxiety as assessed by network analysis. Additionally, microbial depletion with antibiotics also improved the anxiety, microgliosis and BAs enrichment in the experimental MDs mice. Together, these findings provide microbiota–BAs–brain axis as a novel therapeutic target for MDs-associated neuropsychiatric disorders.

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