scholarly journals Aronia melanocarpa polysaccharide ameliorates inflammation and aging in mice by modulating the AMPK/SIRT1/NF-κB signaling pathway and gut microbiota

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yingchun Zhao ◽  
Xinglong Liu ◽  
Yinan Zheng ◽  
Wencong Liu ◽  
Chuanbo Ding
Keyword(s):  
Signaling Pathway ◽  
Brain Tissue ◽  
Brain Aging ◽  
Biological Activities ◽  
Intestinal Flora ◽  
Neurological Deficits ◽  
Aging Brain ◽  
Stress Injury ◽  
Intestinal Microbes ◽  
Aronia Melanocarpa

AbstractAronia melanocarpa is a natural medicinal plant that has a variety of biological activities, its fruit is often used for food and medicine. Aronia melanocarpa polysaccharide (AMP) is the main component of the Aronia melanocarpa fruit. This research evaluated the delay and protection of AMP obtained from Aronia melanocarpa fruit on aging mice by d-Galactose (D-Gal) induction and explored the effect of supplementing AMP on the metabolism of the intestinal flora of aging mice. The aging model was established by intraperitoneal injection of D-Gal (200 mg/kg to 1000 mg/kg) once per 3 days for 12 weeks. AMP (100 and 200 mg/kg) was given daily by oral gavage after 6 weeks of D-Gal-induced. The results showed that AMP treatment significantly improved the spatial learning and memory impairment of aging mice determined by the eight-arm maze test. H&E staining showed that AMP significantly reversed brain tissue pathological damage and structural disorders. AMP alleviated inflammation and oxidative stress injury in aging brain tissue by regulating the AMPK/SIRT1/NF-κB and Nrf2/HO-1 signaling pathways. Particularly, AMP reduced brain cell apoptosis and neurological deficits by activating the PI3K/AKT/mTOR signaling pathway and its downstream apoptotic protein family. Importantly, 16S rDNA analysis indicated the AMP treatment significantly retarded the aging process by improving the composition of intestinal flora and abundance of beneficial bacteria. In summary, this study found that AMP delayed brain aging in mice by inhibiting inflammation and regulating intestinal microbes, which providing the possibility for the amelioration and treatment of aging and related metabolic diseases.

scholarly journals Aronia Melanocarpa Polysaccharide Ameliotates Inflammation and Aging in Mice by Modulating AMPK/SIRT1/NF-κB Signaling Pathway and Gut Microbiota

2021 ◽  
Author(s):  
Yingchun Zhao ◽  
Xinglong Liu ◽  
Yinan Zheng ◽  
Wencong Liu ◽  
Chuanbo Ding
Keyword(s):  
Signaling Pathway ◽  
Brain Tissue ◽  
Brain Aging ◽  
Biological Activities ◽  
Intestinal Flora ◽  
Neurological Deficits ◽  
Aging Brain ◽  
Stress Injury ◽  
Intestinal Microbes ◽  
Aronia Melanocarpa

Abstract Aronia melanocarpa, as a natural medicinal plant, has been widely proved to have a variety of biological activities used as a novel food and medicine. Aronia melanocarpa polysaccharide (AMP) is the main component of the Aronia melanocarpa. The purpose of this research is to evaluate the delay and protection of AMP on aging mice by D-galactose (D-gal) induced, and to explore the effect of supplementing AMP on the metabolism of the intestinal flora of aging organisms.The aging model was established by intraperitoneal injection of D-gal (200 mg/kg to 1000 mg/kg) once per 3 days for 12 weeks, and administer AMP (100 and 200 mg/kg) were given daily by oral gavage after 6 weeks of D-Gal-induced.The results showed that AMP treatment significantly improved the spatial learning and memory impairment of aging mice through the eight-arm maze test, and H&E staining provedthat AMP significantly reversed brain tissue pathological damage and structural disorders.AMP alleviated inflammation and oxidative stress injury in aging brain tissue by regulating AMPK/SIRT1/NF-κB and Nrf2/HO-1 signaling pathways. Particularly, AMP reduced brain cell apoptosis and neurological deficits by activating PI3K/AKT/mTOR signaling pathway and its downstream apoptotic protein family.Importantly, 16S rDNA analysis indicated the AMP treatment significantly redarded the aging process by improving the composition of intestinal flora and abundance of beneficial bacteria. In summary, this study found that AMP delayed brain aging in mice by inhibiting inflammatory and regulating intestinal microbes, which providing the possibility for the amelioration and treatment of aging and related metabolic diseases.

Bioinformatic Analysis Reveals Key Genes and Pathways in Aging Brain of Senescence-accelerated Mouse P8 (SAMP8)

2018 ◽  
Vol 17 (9) ◽  
pp. 712-722 ◽  
Author(s):  
Jiaqi Li ◽  
Yuzhi Zhou ◽  
Guanhua Du ◽  
Xuemei Qin ◽  
Li Gao
Keyword(s):  
Signaling Pathway ◽  
Gene Network ◽  
Brain Aging ◽  
Aging Brain ◽  
Hub Genes ◽  
Qrt Pcr ◽  
Key Genes ◽  
Samp8 Mice ◽  
Key Pathways ◽  
Senescence Accelerated Mouse

Background: Aging is a complex process accompanied with the decline of the different physiological functions. Numerous differentially expressed genes (DEGs) have been found in the aging brain of senescence-accelerated mouse P8 (SAMP8), however, it was challenging to screen out the crucial ones. Objective: This study aimed to explore the crucial genes and pathways in aging brain of SAMP8 mice, which would be beneficial for understanding the pathogenesis of brain aging. Methods: Firstly, 430 genes that are differentially expressed in SAMP8 mice versus SAMR1 mice were obtained from 9 gene expression studies, and gene-gene network was constructed. Clustering analysis and topological analysis were used to single out the hub genes from this network. Secondly, pathway enrichment analysis was utilized to identify the key pathways from the 430 DEGs, and the DEGs in key pathways were considered as functional genes. Thirdly, the inner-network between hub genes and functional genes was constructed, and the key genes were predicted. Parts of the key genes were experimentally verified by quantitative real-time PCR (qRT-PCR), and the associated transcription factors (TFs) were predicted. Results: Our results revealed that 12 crucial genes might affect brain aging, including Trp53, Bcl2, Tnf, Casp9, Fos, Il6, Ptgs2, Il1b, Bdnf, Cdkn1a, Pik3c3, Rps6ka1, among which Casp9, Fos, Ptgs2, Cdkn1a, Pik3c3, and Rps6ka1 had been verified by qRT-PCR in 10-moth-old SAMP8 mice. Five functional groups including mitogen-activated protein kinase (MAPK) signaling pathway, neurotrophin signaling pathway, Hepatitis B, Alzheimer's disease and Oxytocin signaling pathway were significantly changed during aging process in SAMP8 mice. Two key transcription factors of c-Fos and C/EBPbeta were predicted by constructing a TF-target gene network. Conclusion: These putative genes and pathways are closely related to brain senescence and our results would gain new insight into the pathogenesis of brain aging.

Phanginin R Induces Cytoprotective Autophagy via JNK/c-Jun Signaling Pathway in Non-Small Cell Lung Cancer A549 Cells

2020 ◽  
Vol 20 (8) ◽  
pp. 982-988 ◽  
Author(s):  
Le-Le Zhang ◽  
Han Bao ◽  
Yu-Lian Xu ◽  
Xiao-Ming Jiang ◽  
Wei Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Signaling Pathway ◽  
Cell Lung Cancer ◽  
Biological Activities ◽  
A549 Cells ◽  
Immunofluorescence Assay ◽  
Small Cell ◽  
Autophagic Flux ◽  
Small Cell Lung

Background: Cassane-type diterpenoids are widely distributed in the medical plants of genus Caesalpinia. To date, plenty of cassane diterpenoids have been isolated from the genus Caesalpinia, and some of them were documented to exhibit multiple biological activities. However, the effects of these compounds on autophagy have never been reported. Objective: To investigate the effects and mechanisms of the cassane diterpenoids including Phanginin R (PR) on autophagy in Non-Small Cell Lung Cancer (NSCLC) A549 cells. Methods: Western blot analysis and immunofluorescence assay were performed to investigate the effects of the compounds on autophagic flux in A549 cells. The pathway inhibitor and siRNA interference were used to investigate the mechanism of PR. MTT assay was performed to detect cell viability. Results: PR treatment upregulated the expression of phosphatidylethanolamine-modified microtubule-associated protein Light-Chain 3 (LC3-II) in A549 cells. Immunofluorescence assay showed that PR treatment increased the production of red-fluorescent puncta in mRFP-GFP-LC3 plasmid-transfected cells, indicating PR promoted autophagic flux in A549 cells. PR treatment activated the c-Jun N-terminal Kinase (JNK) signaling pathway while it did not affect the classical Akt/mammalian Target of Rapamycin (mTOR) pathway. Pretreatment with the JNK inhibitor SP600125 or siRNA targeting JNK or c-Jun suppressed PR-induced autophagy. In addition, cotreatment with the autophagy inhibitor Chloroquine (CQ) or inhibition of the JNK/c-Jun signaling pathway increased PR-induced cytotoxicity. Conclusion: PR induced cytoprotective autophagy in NSCLC A549 cells via the JNK/c-Jun signaling pathway, and autophagy inhibition could further improve the anti-cancer potential of PR.

scholarly journals Chromosome Instability, Aging and Brain Diseases

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1256
Author(s):  
Ivan Y. Iourov ◽  
Yuri B. Yurov ◽  
Svetlana G. Vorsanova ◽  
Sergei I. Kutsev
Keyword(s):  
Brain Aging ◽  
Chromosome Instability ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Accelerated Aging ◽  
Brain Diseases ◽  
Aging Brain ◽  
Ontogenetic Changes ◽  
Health And Disease

Chromosome instability (CIN) has been repeatedly associated with aging and progeroid phenotypes. Moreover, brain-specific CIN seems to be an important element of pathogenic cascades leading to neurodegeneration in late adulthood. Alternatively, CIN and aneuploidy (chromosomal loss/gain) syndromes exhibit accelerated aging phenotypes. Molecularly, cellular senescence, which seems to be mediated by CIN and aneuploidy, is likely to contribute to brain aging in health and disease. However, there is no consensus about the occurrence of CIN in the aging brain. As a result, the role of CIN/somatic aneuploidy in normal and pathological brain aging is a matter of debate. Still, taking into account the effects of CIN on cellular homeostasis, the possibility of involvement in brain aging is highly likely. More importantly, the CIN contribution to neuronal cell death may be responsible for neurodegeneration and the aging-related deterioration of the brain. The loss of CIN-affected neurons probably underlies the contradiction between reports addressing ontogenetic changes of karyotypes within the aged brain. In future studies, the combination of single-cell visualization and whole-genome techniques with systems biology methods would certainly define the intrinsic role of CIN in the aging of the normal and diseased brain.

scholarly journals Sea urchin larvae utilize light for regulating the pyloric opening

BMC Biology ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Junko Yaguchi ◽  
Shunsuke Yaguchi
Keyword(s):  
Signaling Pathway ◽  
Digestive Tract ◽  
Sea Urchin ◽  
Visual Information ◽  
Biological Activities ◽  
Regulatory System ◽  
Sister Group ◽  
Animal Evolution ◽  
Deuterostome Evolution ◽  
Visual Systems

Abstract Background Light is essential for various biological activities. In particular, visual information through eyes or eyespots is very important for most of animals, and thus, the functions and developmental mechanisms of visual systems have been well studied to date. In addition, light-dependent non-visual systems expressing photoreceptor Opsins have been used to study the effects of light on diverse animal behaviors. However, it remains unclear how light-dependent systems were acquired and diversified during deuterostome evolution due to an almost complete lack of knowledge on the light-response signaling pathway in Ambulacraria, one of the major groups of deuterostomes and a sister group of chordates. Results Here, we show that sea urchin larvae utilize light for digestive tract activity. We found that photoirradiation of larvae induces pyloric opening even without addition of food stimuli. Micro-surgical and knockdown experiments revealed that this stimulating light is received and mediated by Go(/RGR)-Opsin (Opsin3.2 in sea urchin genomes) cells around the anterior neuroectoderm. Furthermore, we found that the anterior neuroectodermal serotoninergic neurons near Go-Opsin-expressing cells are essential for mediating light stimuli-induced nitric oxide (NO) release at the pylorus. Our results demonstrate that the light>Go-Opsin>serotonin>NO pathway functions in pyloric opening during larval stages. Conclusions The results shown here will lead us to understand how light-dependent systems of pyloric opening functioning via neurotransmitters were acquired and established during animal evolution. Based on the similarity of nervous system patterns and the gut proportions among Ambulacraria, we suggest the light>pyloric opening pathway may be conserved in the clade, although the light signaling pathway has so far not been reported in other members of the group. In light of brain-gut interactions previously found in vertebrates, we speculate that one primitive function of anterior neuroectodermal neurons (brain neurons) may have been to regulate the function of the digestive tract in the common ancestor of deuterostomes. Given that food consumption and nutrient absorption are essential for animals, the acquirement and development of brain-based sophisticated gut regulatory system might have been important for deuterostome evolution.

Aging Brain, Aging Mind

1992 ◽  
Vol 267 (3) ◽  
pp. 134-142 ◽  
Author(s):  
Dennis J. Selkoe
Keyword(s):  
Brain Aging ◽  
Aging Brain

scholarly journals A fiber-deprived diet causes cognitive impairment and hippocampal microglia-mediated synaptic loss through the gut microbiota and metabolites

Microbiome ◽  
2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Hongli Shi ◽  
Xing Ge ◽  
Xi Ma ◽  
Mingxuan Zheng ◽  
Xiaoying Cui ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Gut Microbiota ◽  
Neurodegenerative Diseases ◽  
Dietary Fiber ◽  
Brain Aging ◽  
Synaptic Proteins ◽  
Aging Brain ◽  
Normal Brain ◽  
Fiber Intake ◽  
Synaptic Ultrastructure

Abstract Background Cognitive impairment, an increasing mental health issue, is a core feature of the aging brain and neurodegenerative diseases. Industrialized nations especially, have experienced a marked decrease in dietary fiber intake, but the potential mechanism linking low fiber intake and cognitive impairment is poorly understood. Emerging research reported that the diversity of gut microbiota in Western populations is significantly reduced. However, it is unknown whether a fiber-deficient diet (which alters gut microbiota) could impair cognition and brain functional elements through the gut-brain axis. Results In this study, a mouse model of long-term (15 weeks) dietary fiber deficiency (FD) was used to mimic a sustained low fiber intake in humans. We found that FD mice showed impaired cognition, including deficits in object location memory, temporal order memory, and the ability to perform daily living activities. The hippocampal synaptic ultrastructure was damaged in FD mice, characterized by widened synaptic clefts and thinned postsynaptic densities. A hippocampal proteomic analysis further identified a deficit of CaMKIId and its associated synaptic proteins (including GAP43 and SV2C) in the FD mice, along with neuroinflammation and microglial engulfment of synapses. The FD mice also exhibited gut microbiota dysbiosis (decreased Bacteroidetes and increased Proteobacteria), which was significantly associated with the cognitive deficits. Of note, a rapid differentiating microbiota change was observed in the mice with a short-term FD diet (7 days) before cognitive impairment, highlighting a possible causal impact of the gut microbiota profile on cognitive outcomes. Moreover, the FD diet compromised the intestinal barrier and reduced short-chain fatty acid (SCFA) production. We exploit these findings for SCFA receptor knockout mice and oral SCFA supplementation that verified SCFA playing a critical role linking the altered gut microbiota and cognitive impairment. Conclusions This study, for the first time, reports that a fiber-deprived diet leads to cognitive impairment through altering the gut microbiota-hippocampal axis, which is pathologically distinct from normal brain aging. These findings alert the adverse impact of dietary fiber deficiency on brain function, and highlight an increase in fiber intake as a nutritional strategy to reduce the risk of developing diet-associated cognitive decline and neurodegenerative diseases.

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