scholarly journals Guarana (Paullinia cupana) Extract Protects Caenorhabditis elegans Models for Alzheimer Disease and Huntington Disease through Activation of Antioxidant and Protein Degradation Pathways

2018 ◽  
Vol 2018 ◽  
pp. 1-16 ◽  
Author(s):  
Patrícia Ferreira Boasquívis ◽  
Giovanna Melo Martins Silva ◽  
Franciny Aparecida Paiva ◽  
Rodrigo Marinho Cavalcanti ◽  
Cecília Verônica Nunez ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Protein Misfolding ◽  
Therapeutic Potential ◽  
High Energy ◽  
Protective Effects ◽  
Independent Manner ◽  
Paullinia Cupana ◽  
Age Related ◽  
Polyq Protein ◽  
Underlying Mechanisms

Guarana (Paullinia cupana) is largely consumed in Brazil in high energy drinks and dietary supplements because of its stimulant activity on the central nervous system. Although previous studies have indicated that guarana has some protective effects in Parkinson’s (PD), Alzheimer’s (AD), and Huntington’s (HD) disease models, the underlying mechanisms are unknown. Here, we investigated the protective effects of guarana hydroalcoholic extract (GHE) in Caenorhabditis elegans models of HD and AD. GHE reduced polyglutamine (polyQ) protein aggregation in the muscle and also reduced polyQ-mediated neuronal death in ASH sensory neurons and delayed β-amyloid-induced paralysis in a caffeine-independent manner. Moreover, GHE’s protective effects were not mediated by caloric restriction, antimicrobial effects, or development and reproduction impairment. Inactivation of the transcription factors SKN-1 and DAF-16 by RNAi partially blocked the protective effects of GHE treatment in the AD model. We show that the protective effect of GHE is associated with antioxidant activity and modulation of proteostasis, since it increased the lifespan and proteasome activity, reduced intracellular ROS and the accumulation of autophagosomes, and increased the expression of SOD-3 and HSP-16.2. Our findings suggest that GHE has therapeutic potential in combating age-related diseases associated with protein misfolding and accumulation.

Microglial autophagy–associated phagocytosis is essential for recovery from neuroinflammation

2020 ◽  
Vol 5 (52) ◽  
pp. eabb5077
Author(s):  
Rasmus Berglund ◽  
Andre Ortlieb Guerreiro-Cacais ◽  
Milena Z. Adzemovic ◽  
Manuel Zeitelhofer ◽  
Harald Lund ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Wild Type ◽  
Cns Inflammation ◽  
Age Related ◽  
Microglial Phenotype ◽  
The Central Nervous System ◽  
Underlying Mechanisms ◽  
Myelin Degradation ◽  
Specific Deletion ◽  
Noncanonical Form

Multiple sclerosis (MS) is a leading cause of incurable progressive disability in young adults caused by inflammation and neurodegeneration in the central nervous system (CNS). The capacity of microglia to clear tissue debris is essential for maintaining and restoring CNS homeostasis. This capacity diminishes with age, and age strongly associates with MS disease progression, although the underlying mechanisms are still largely elusive. Here, we demonstrate that the recovery from CNS inflammation in a murine model of MS is dependent on the ability of microglia to clear tissue debris. Microglia-specific deletion of the autophagy regulator Atg7, but not the canonical macroautophagy protein Ulk1, led to increased intracellular accumulation of phagocytosed myelin and progressive MS-like disease. This impairment correlated with a microglial phenotype previously associated with neurodegenerative pathologies. Moreover, Atg7-deficient microglia showed notable transcriptional and functional similarities to microglia from aged wild-type mice that were also unable to clear myelin and recover from disease. In contrast, induction of autophagy in aged mice using the disaccharide trehalose found in plants and fungi led to functional myelin clearance and disease remission. Our results demonstrate that a noncanonical form of autophagy in microglia is responsible for myelin degradation and clearance leading to recovery from MS-like disease and that boosting this process has a therapeutic potential for age-related neuroinflammatory conditions.

scholarly journals Exosomes and Micro-RNAs in Aging Process

Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 968
Author(s):  
Yousra Hamdan ◽  
Loubna Mazini ◽  
Gabriel Malka
Keyword(s):  
Messenger Rna ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Biological Fluids ◽  
Cell Types ◽  
Exosome Biogenesis ◽  
Age Related ◽  
Micro Rnas ◽  
Underlying Mechanisms ◽  
Almost All

Exosomes are the main actors of intercellular communications and have gained great interest in the new cell-free regenerative medicine. These nanoparticles are secreted by almost all cell types and contain lipids, cytokines, growth factors, messenger RNA, and different non-coding RNA, especially micro-RNAs (mi-RNAs). Exosomes’ cargo is released in the neighboring microenvironment but is also expected to act on distant tissues or organs. Different biological processes such as cell development, growth and repair, senescence, migration, immunomodulation, and aging, among others, are mediated by exosomes and principally exosome-derived mi-RNAs. Moreover, their therapeutic potential has been proved and reinforced by their use as biomarkers for disease diagnostics and progression. Evidence has increasingly shown that exosome-derived mi-RNAs are key regulators of age-related diseases, and their involvement in longevity is becoming a promising issue. For instance, mi-RNAs such as mi-RNA-21, mi-RNA-29, and mi-RNA-34 modulate tissue functionality and regeneration by targeting different tissues and involving different pathways but might also interfere with long life expectancy. Human mi-RNAs profiling is effectively related to the biological fluids that are reported differently between young and old individuals. However, their underlying mechanisms modulating cell senescence and aging are still not fully understood, and little was reported on the involvement of mi-RNAs in cell or tissue longevity. In this review, we summarize exosome biogenesis and mi-RNA synthesis and loading mechanism into exosomes’ cargo. Additionally, we highlight the molecular mechanisms of exosomes and exosome-derived mi-RNA regulation in the different aging processes.

scholarly journals Neuroprotective Effects of Glochidion zeylanicum Leaf Extract against H2O2/Glutamate-Induced Toxicity in Cultured Neuronal Cells and Aβ-Induced Toxicity in Caenorhabditis elegans

Biology ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 800
Author(s):  
Chatrawee Duangjan ◽  
Panthakarn Rangsinth ◽  
Shaoxiong Zhang ◽  
Xiaojie Gu ◽  
Michael Wink ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Caenorhabditis Elegans ◽  
Leaf Extract ◽  
Neuronal Cells ◽  
Antioxidant Properties ◽  
Ros Generation ◽  
Protective Effects ◽  
Neuroprotective Effects ◽  
Antioxidant Genes ◽  
Age Related

Oxidative stress plays a crucial role in the development of age-related neurodegenerative diseases. Previously, Glochidion zeylanicum methanol (GZM) extract has been reported to have antioxidant and anti-aging properties. However, the effect of GZM on neuroprotection has not been reported yet; furthermore, the mechanism involved in its antioxidant properties remains unresolved. The study is aimed to demonstrate the neuroprotective properties of GZM extract and their underlying mechanisms in cultured neuronal (HT-22 and Neuro-2a) cells and Caenorhabditis elegans models. GZM extract exhibited protective effects against glutamate/H2O2-induced toxicity in cultured neuronal cells by suppressing the intracellular reactive oxygen species (ROS) generation and enhancing the expression of endogenous antioxidant enzymes (SODs, GPx, and GSTs). GZM extract also triggered the expression of SIRT1/Nrf2 proteins and mRNA transcription of antioxidant genes (NQO1, GCLM, and EAAT3) which are the master regulators of cellular defense against oxidative stress. Additionally, GZM extract exhibited protective effects to counteract β-amyloid (Aβ)-induced toxicity in C. elegans and promoted neuritogenesis properties in Neuro-2a cells. Our observations suggest that GZM leaf extract has interesting neuritogenesis and neuroprotective potential and can possibly act as potential contender for the treatment of oxidative stress-induced Alzheimer’s disease (AD) and related neurodegenerative conditions; however, this needs to be studied further in other in vivo systems.

scholarly journals NMN Rescues Endothelial Function and Neurovascular Coupling, Improving Cognitive Function in Aged Mice

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 121-121
Author(s):  
Stefano Tarantini ◽  
Andriy Yabluchanskiy ◽  
Praveen Ballabh ◽  
Eszter Farkas ◽  
Joseph Baur ◽  
...  
Keyword(s):  
Cognitive Function ◽  
Cognitive Decline ◽  
Spatial Working Memory ◽  
Therapeutic Potential ◽  
Critical Role ◽  
Neurovascular Coupling ◽  
Protective Effects ◽  
Doppler Flowmetry ◽  
Aged Mice ◽  
Age Related

Abstract Adjustment of cerebral blood flow (CBF) to neuronal activity via neurovascular coupling (NVC) has an essential role in maintenance of healthy cognitive function. In aging increased oxidative stress and cerebromicrovascular endothelial dysfunction impair NVC, contributing to cognitive decline. There is increasing evidence showing that a decrease in NAD+ availability with age plays a critical role in a range of age-related cellular impairments but its role in impaired NVC responses remains unexplored. The present study was designed to test the hypothesis that restoring NAD+ concentration may exert beneficial effects on NVC responses in aging. To test this hypothesis 24-month-old C57BL/6 mice were treated with nicotinamide mononucleotide (NMN), a key NAD+ intermediate, for 2 weeks. NVC was assessed by measuring CBF responses (laser Doppler flowmetry) evoked by contralateral whisker stimulation. We found that NVC responses were significantly impaired in aged mice. NMN supplementation rescued NVC responses by increasing endothelial NO-mediated vasodilation, which was associated with significantly improved spatial working memory and gait coordination. These findings are paralleled by the sirtuin-dependent protective effects of NMN on mitochondrial production of reactive oxygen species and mitochondrial bioenergetics in cultured cerebromicrovascular endothelial cells derived from aged animals. Thus, a decrease in NAD+ availability contributes to age-related cerebromicrovascular dysfunction, exacerbating cognitive decline. The cerebromicrovascular protective effects of NMN highlight the preventive and therapeutic potential of NAD+ intermediates as effective interventions in patients at risk for vascular cognitive impairment (VCI).

scholarly journals Spatiotemporal regulation of autophagy during Caenorhabditis elegans aging

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Jessica T Chang ◽  
Caroline Kumsta ◽  
Andrew B Hellman ◽  
Linnea M Adams ◽  
Malene Hansen
Keyword(s):  
Caenorhabditis Elegans ◽  
Body Wall ◽  
Lifespan Extension ◽  
Autophagic Flux ◽  
Wild Type ◽  
C Elegans ◽  
Spatiotemporal Regulation ◽  
Age Related ◽  
Autophagic Activity ◽  
Underlying Mechanisms

Autophagy has been linked to longevity in many species, but the underlying mechanisms are unclear. Using a GFP-tagged and a new tandem-tagged Atg8/LGG-1 reporter, we quantified autophagic vesicles and performed autophagic flux assays in multiple tissues of wild-type Caenorhabditis elegans and long-lived daf-2/insulin/IGF-1 and glp-1/Notch mutants throughout adulthood. Our data are consistent with an age-related decline in autophagic activity in the intestine, body-wall muscle, pharynx, and neurons of wild-type animals. In contrast, daf-2 and glp-1 mutants displayed unique age- and tissue-specific changes in autophagic activity, indicating that the two longevity paradigms have distinct effects on autophagy during aging. Although autophagy appeared active in the intestine of both long-lived mutants, inhibition of intestinal autophagy significantly abrogated lifespan extension only in glp-1 mutants. Collectively, our data suggest that autophagic activity normally decreases with age in C. elegans, whereas daf-2 and glp-1 long-lived mutants regulate autophagy in distinct spatiotemporal-specific manners to extend lifespan.

scholarly journals Maintenance of type 2 glycolytic myofibers with age by Mib1-Actn3 axis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ji-Yun Seo ◽  
Jong-Seol Kang ◽  
Ye Lynne Kim ◽  
Young-Woo Jo ◽  
Ji-Hoon Kim ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Atrophy ◽  
Muscle Function ◽  
Therapeutic Potential ◽  
Chronic Exercise ◽  
Skeletal Muscle Function ◽  
Age Related ◽  
Underlying Mechanisms ◽  
Exercise Induced

AbstractAge-associated muscle atrophy is a debilitating condition associated with loss of muscle mass and function with age that contributes to limitation of mobility and locomotion. However, the underlying mechanisms of how intrinsic muscle changes with age are largely unknown. Here we report that, with age, Mind bomb-1 (Mib1) plays important role in skeletal muscle maintenance via proteasomal degradation-dependent regulation of α-actinin 3 (Actn3). The disruption of Mib1 in myofibers (Mib1ΔMF) results in alteration of type 2 glycolytic myofibers, muscle atrophy, impaired muscle function, and Actn3 accumulation. After chronic exercise, Mib1ΔMF mice show muscle atrophy even at young age. However, when Actn3 level is downregulated, chronic exercise-induced muscle atrophy is ameliorated. Importantly, the Mib1 and Actn3 levels show clinical relevance in human skeletal muscles accompanied by decrease in skeletal muscle function with age. Together, these findings reveal the significance of the Mib1-Actn3 axis in skeletal muscle maintenance with age and suggest the therapeutic potential for the treatment or amelioration of age-related muscle atrophy.

scholarly journals Oolonghomobisflavans from Camellia sinensis increase Caenorhabditis elegans lifespan and healthspan

GeroScience ◽  
2021 ◽  
Author(s):  
Chatrawee Duangjan ◽  
Sean P. Curran
Keyword(s):  
Caenorhabditis Elegans ◽  
Camellia Sinensis ◽  
Healthy Aging ◽  
Health Benefits ◽  
Normal Diet ◽  
Bioactive Molecules ◽  
Protective Effects ◽  
Oolong Tea ◽  
Age Related ◽  
Antioxidant Agents

AbstractTea polyphenols are widely considered as excellent antioxidant agents which can contribute to human health and longevity. However, the identification of the active biomolecules in complex tea extracts that promote health and longevity are not fully known. Here we used the nematode Caenorhabditis elegans to analyze the health benefits and longevity effects of Camellia sinensis oolong tea extracts (QFT, NFT, and CFT) and oolonghomobisflavan A and oolonghomobisflavan B, which are present in oolong tea extracts. Our results showed that oolong tea extracts and oolonghomobisflavans prolong lifespan and improved healthspan by curtailing the age-related decline in muscle activity and the accumulation of age pigment (lipofuscin). We found that the lifespan and healthspan promoting effects of oolong tea extracts and oolonghomobisflavans were positively correlated with the stress resistance via DAF-16/FOXO transcription factor. Furthermore, oolong tea extracts and oolonghomobisflavans displayed protective effects against Aβ- and polyQ-induced neuro/proteotoxicity. Overall, our study provides new evidence to support the health benefits of oolong tea and importantly identify oolonghomobisflavans as potent bioactive molecules that promote health when supplemented with a normal diet. As such, oolonghomobisflavans represent a valuable new class of compounds that promote healthy aging.

scholarly journals Methionine Restriction Prevents Lipopolysaccharide-Induced Acute Lung Injury via Modulating CSE/H2S Pathway

Nutrients ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 322
Author(s):  
Jiaxiang Duan ◽  
Lunli Xiang ◽  
Zhen Yang ◽  
Li Chen ◽  
Jianteng Gu ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Immune Cell ◽  
Therapeutic Potential ◽  
Alveolar Epithelial Cell ◽  
Receptor Protein ◽  
Protective Effects ◽  
Methionine Restriction ◽  
Production Of Hydrogen ◽  
Underlying Mechanisms

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) result in high mortality, whereas effective treatments are limited. Methionine restriction (MR) has been reported to offer various benefits against multiple pathological processes of organ injuries. However, it remains unknown whether MR has any potential therapeutic value for ALI/ARDS. The current study was set to investigate the therapeutic potential of MR on lipopolysaccharide (LPS)-induced ALI and its underlying mechanisms. We found that MR attenuated LPS-induced pulmonary edema, hemorrhage, atelectasis, and alveolar epithelial cell injuries in mice. MR upregulated cystathionine-gamma-lyase (CSE) expression and enhanced the production of hydrogen sulfide (H2S). MR also inhibited the activation of Toll-like receptors 4 (TLR4)/NF-κB/NOD-like receptor protein 3 (NLRP3), then reduced IL-1β, IL-6, and TNF-α release and immune cell infiltration. Moreover, the protective effects of MR on LPS-induced ALI were abrogated by inhibiting CSE, whereas exogenous H2S treatment alone mimicked the protective effects of MR in Cse−/− mice after LPS administration. In conclusion, our findings showed that MR attenuated LPS-induced lung injury through CSE and H2S modulation. This work suggests that developing MR towards clinical use for ALI/ARDS patients may be a valuable strategy.

Current Advances in the Biological Activity of Polysaccharides in Dendrobium with Intriguing Therapeutic Potential

2018 ◽  
Vol 25 (14) ◽  
pp. 1663-1681 ◽  
Author(s):  
Chun-Ting Lee ◽  
Heng-Chun Kuo ◽  
Yung-Hsiang Chen ◽  
Ming-Yen Tsai
Keyword(s):  
Biological Activity ◽  
Therapeutic Potential ◽  
Biological Activities ◽  
Biological Effects ◽  
Herbal Medicines ◽  
Research Field ◽  
Protective Effects ◽  
Pharmacological Effects ◽  
The Family ◽  
Anti Tumor Activity

The polysaccharides in many plants are attracting worldwide attention because of their biological activities and medical properties, such as anti-viral, anti-oxidative, antichronic inflammation, anti-hypertensive, immunomodulation, and neuron-protective effects, as well as anti-tumor activity. Denodrobium species, a genus of the family orchidaceae, have been used as herbal medicines for hundreds of years in China due to their pharmacological effects. These effects include nourishing the Yin, supplementing the stomach, increasing body fluids, and clearing heat. Recently, numerous researchers have investigated possible active compounds in Denodrobium species, such as lectins, phenanthrenes, alkaloids, trigonopol A, and polysaccharides. Unlike those of other plants, the biological effects of polysaccharides in Dendrobium are a novel research field. In this review, we focus on these novel findings to give readers an overall picture of the intriguing therapeutic potential of polysaccharides in Dendrobium, especially those of the four commonly-used Denodrobium species: D. huoshanense, D. offininale, D. nobile, and D. chrysotoxum.

Anthocyanins As Modulators of Cell Redox-Dependent Pathways in Non-Communicable Diseases

2020 ◽  
Vol 27 (12) ◽  
pp. 1955-1996 ◽  
Author(s):  
Antonio Speciale ◽  
Antonella Saija ◽  
Romina Bashllari ◽  
Maria Sofia Molonia ◽  
Claudia Muscarà ◽  
...  
Keyword(s):  
Human Health ◽  
Biological Activities ◽  
Wide Spectrum ◽  
Antioxidant Defenses ◽  
Noncommunicable Diseases ◽  
Protective Effects ◽  
Pathological Conditions ◽  
Chronic Pulmonary Diseases ◽  
Underlying Mechanisms

: Chronic Noncommunicable Diseases (NCDs), mostly represented by cardiovascular diseases, diabetes, chronic pulmonary diseases, cancers, and several chronic pathologies, are one of the main causes of morbidity and mortality, and are mainly related to the occurrence of metabolic risk factors. Anthocyanins (ACNs) possess a wide spectrum of biological activities, such as anti-inflammatory, antioxidant, cardioprotective and chemopreventive properties, which are able to promote human health. Although ACNs present an apparent low bioavailability, their metabolites may play an important role in the in vivo protective effects observed. : This article directly addresses the scientific evidences supporting that ACNs could be useful to protect human population against several NCDs not only acting as antioxidant but through their capability to modulate cell redox-dependent signaling. In particular, ACNs interact with the NF-κB and AP-1 signal transduction pathways, which respond to oxidative signals and mediate a proinflammatory effect, and the Nrf2/ARE pathway and its regulated cytoprotective proteins (GST, NQO, HO-1, etc.), involved in both cellular antioxidant defenses and elimination/inactivation of toxic compounds, so countering the alterations caused by conditions of chemical/oxidative stress. In addition, supposed crosstalks could contribute to explain the protective effects of ACNs in different pathological conditions characterized by an altered balance among these pathways. Thus, this review underlines the importance of specific nutritional molecules for human health and focuses on the molecular targets and the underlying mechanisms of ACNs against various diseases.

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