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https://www.readbyqxmd.com/read/28820880/knock-out-of-a-mitochondrial-sirtuin-protects-neurons-from-degeneration-in-caenorhabditis-elegans
#1
Rachele Sangaletti, Massimo D'Amico, Jeff Grant, David Della-Morte, Laura Bianchi
Sirtuins are NAD⁺-dependent deacetylases, lipoamidases, and ADP-ribosyltransferases that link cellular metabolism to multiple intracellular pathways that influence processes as diverse as cell survival, longevity, and cancer growth. Sirtuins influence the extent of neuronal death in stroke. However, different sirtuins appear to have opposite roles in neuronal protection. In Caenorhabditis elegans, we found that knock-out of mitochondrial sirtuin sir-2.3, homologous to mammalian SIRT4, is protective in both chemical ischemia and hyperactive channel induced necrosis...
August 18, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28815872/a-multimethod-computational-simulation-approach-for-investigating-mitochondrial-dynamics-and-dysfunction-in-degenerative-aging
#2
Timothy E Hoffman, Katherine J Barnett, Lyle Wallis, William H Hanneman
Research in biogerontology has largely focused on the complex relationship between mitochondrial dysfunction and biological aging. In particular, the mitochondrial free radical theory of aging (MFRTA) has been well accepted. However, this theory has been challenged by recent studies showing minimal increases in reactive oxygen species (ROS) as not entirely deleterious in nature, and even beneficial under the appropriate cellular circumstances. To assess these significant and nonintuitive observations in the context of a functional system, we have taken an in silico approach to expand the focus of the MFRTA by including other key mitochondrial stress response pathways, as they have been observed in the nematode Caenorhabditis elegans...
August 16, 2017: Aging Cell
https://www.readbyqxmd.com/read/28794203/the-myst-family-histone-acetyltransferase-complex-regulates-stress-resistance-and-longevity-through-transcriptional-control-of-daf-16-foxo-transcription-factors
#3
Takako Ikeda, Masaharu Uno, Sakiko Honjoh, Eisuke Nishida
The well-known link between longevity and the Sir2 histone deacetylase family suggests that histone deacetylation, a modification associated with repressed chromatin, is beneficial to longevity. However, the molecular links between histone acetylation and longevity remain unclear. Here, we report an unexpected finding that the MYST family histone acetyltransferase complex (MYS-1/TRR-1 complex) promotes rather than inhibits stress resistance and longevity in Caenorhabditis elegans Our results show that these beneficial effects are largely mediated through transcriptional up-regulation of the FOXO transcription factor DAF-16...
August 9, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28775361/a-conserved-neuronal-daf-16-foxo-plays-an-important-role-in-conveying-pheromone-signals-to-elicit-repulsion-behavior-in-caenorhabditis-elegans
#4
Donha Park, Jeong-Hoon Hahm, Saeram Park, Go Ha, Gyeong-Eon Chang, Haelim Jeong, Heekyeong Kim, Sunhee Kim, Eunji Cheong, Young-Ki Paik
Animals use pheromones as a conspecific chemical language to respond appropriately to environmental changes. The soil nematode Caenorhabditis elegans secretes ascaroside pheromones throughout the lifecycle, which influences entry into dauer phase in early larvae, in addition to sexual attraction and aggregation. In adult hermaphrodites, pheromone sensory signals perceived by worms usually elicit repulsion as an initial behavioral signature. However, the molecular mechanisms underlying neuronal pheromone sensory process from perception to repulsion in adult hermaphrodites remain poorly understood...
August 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28766017/pmk-1-p38-mapk-promotes-cadmium-stress-resistance-the-expression-of-skn-1-nrf-and-daf-16-target-genes-and-protein-biosynthesis-in-caenorhabditis-elegans
#5
Alex Keshet, Ansgar Mertenskötter, Sarah A Winter, Vanessa Brinkmann, Ramona Dölling, Rüdiger J Paul
The mechanisms of cadmium (Cd) resistance are complex and not sufficiently understood. The present study, therefore, aimed at assessing the roles of important components of stress-signaling pathways and of ABC transporters under severe Cd stress in Caenorhabditis elegans. Survival assays on mutant and control animals revealed a significant promotion of Cd resistance by the PMK-1 p38 MAP kinase, the transcription factor DAF-16/FoxO, and the ABC transporter MRP-1. Transcriptome profiling by RNA-Seq on wild type and a pmk-1 mutant under control and Cd stress conditions revealed, inter alia, a PMK-1-dependent promotion of gene expression for the translational machinery...
August 1, 2017: Molecular Genetics and Genomics: MGG
https://www.readbyqxmd.com/read/28758742/effects-of-c-glycosides-from-apios-americana-leaves-against-oxidative-stress-during-hyperglycemia-through-regulating-mitogen-activated-protein-kinases-and-nuclear-factor-erythroid-2-related-factor-2
#6
Fujie Yan, Yunyun Yang, Lushuang Yu, Xiaodong Zheng
Main components of Apios americana leaves extract (ALE) were flavonoid C-glycosides, including vitexin (46.7%), schaftoside (18.9%), and orientin (4.32%). In vitro, ALE restored glucose consumption, glucose uptake, and glycogen content in glucose-induced hepatic cells. Exposure of HepG2 cells to high glucose resulted in reactive oxygen species and O2(-) accumulation, while ALE alleviated these increases by 47 ± 0.68 and 68 ± 0.74%, respectively. Glucose increased c-Jun N-terminal kinase (JNK) and decreased extracellular signal-regulated kinases 1 and 2 (ERK1/2) and p38 phosphorylation, while ALE reduced p-JNK and p-p38 but not p-ERK1/2, accompanied by nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1, and NAD(P)H quinine oxidoreductase 1 downregulation...
August 16, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28713491/mulberry-anthocyanin-extract-ameliorates-oxidative-damage-in-hepg2-cells-and-prolongs-the-lifespan-of-caenorhabditis-elegans-through-mapk-and-nrf2-pathways
#7
Fujie Yan, Yushu Chen, Ramila Azat, Xiaodong Zheng
Mulberry anthocyanins possess many pharmacological effects including liver protection, anti-inflammation, and anticancer. The aim of this study was to evaluate whether mulberry anthocyanin extract (MAE) exerts beneficial effects against oxidative stress damage in HepG2 cells and Caenorhabditis elegans. In vitro, MAE prevented cytotoxicity, increased glucose consumption and uptake, and eliminated excessive intracellular free radicals in H2O2-induced cells. Moreover, MAE pretreatment maintained Nrf2, HO-1, and p38 MAPK stimulation and abolished upregulation of p-JNK, FOXO1, and PGC-1α that were involved in oxidative stress and insulin signalling modulation...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28696216/regulation-of-lysosomal-function-by-the-daf-16-forkhead-transcription-factor-couples-reproduction-to-aging-in-caenorhabditis-elegans
#8
Kunal Baxi, Ata Ghavidel, Brandon Waddell, Troy A Harkness, Carlos E de Carvalho
Aging in eukaryotes is accompanied by widespread deterioration of the somatic tissue. Yet, abolishing germ cells delays the age-dependent somatic decline in Caenorhabditis elegans In adult worms lacking germ cells, the activation of the DAF-9/DAF-12 steroid signalling pathway in the gonad recruits DAF-16 activity in the intestine to promote longevity-associated phenotypes. However, the impact of this pathway on the fitness of normally reproducing animals is less clear. Here, we explore the link between progeny production and somatic aging and identify the loss of lysosomal acidity, a critical regulator of the proteolytic output of these organelles, as a novel biomarker of aging in C...
July 10, 2017: Genetics
https://www.readbyqxmd.com/read/28676501/lifespan-extension-by-peroxidase-dual-oxidase-mediated-ros-signaling-through-pyrroloquinoline-quinone-in-c-elegans
#9
Hiroyuki Sasakura, Hiroki Moribe, Masahiko Nakano, Kazuto Ikemoto, Kosei Takeuchi, Ikue Mori
Reactive oxygen species (ROS), originally characterized based on their harmful effects on cells or organisms, are now recognized as important signal molecules regulating various biological processes. In particular, low levels of ROS released from mitochondria extend lifespan. Here, we identified a novel mechanism of generating appropriate levels of ROS at the plasma membrane through a peroxidase/dual oxidase system, which could extend lifespan in Caenorhabditis elegans (C. elegans). A redox co-factor, pyrroloquinoline quinone (PQQ), activates dual oxidase (DUOX)/BLI-3 to produce the ROS H2O2 at the plasma membrane, which is subsequently degraded by peroxidase/MLT-7, eventually ensuring the adequate levels of ROS...
July 4, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28669960/-effect-of-herba-scutellariae-barbatae-flavonoids-in-delaying-aging-of-caenorhabditis-elegans-and-human-umbilical-vein-endothelial-cells-in-vitro
#10
Wei Zhou, Jing-Ming Lin, Su-Li Wang, Hai-Zhen Lin
OBJECTIVE: To explore the effects of Herba Scutellariae Barbatae flavonoids (HF) in delaying aging of Caenorhabditis elegans and human umbilical vein endothelial cells (HUVECs) in vitro. METHODS: The effects of 30 or 50 mg/L of HF on nematode life span, reproductive capacity, oxidative stress, and antioxidant enzyme activity of C. elegans were assessed, and the effects of HF on the expressions of the genes encoding antioxidant enzymes and the aging-related genes were analyzed using real-time RT-PCR in both C...
June 20, 2017: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
https://www.readbyqxmd.com/read/28638078/the-stress-response-factor-daf-16-foxo-is-required-for-multiple-compound-families-to-prolong-the-function-of-neurons-with-huntington-s-disease
#11
Francesca Farina, Emmanuel Lambert, Lucie Commeau, François-Xavier Lejeune, Nathalie Roudier, Cosima Fonte, J Alex Parker, Jacques Boddaert, Marc Verny, Etienne-Emile Baulieu, Christian Neri
Helping neurons to compensate for proteotoxic stress and maintain function over time (neuronal compensation) has therapeutic potential in aging and neurodegenerative disease. The stress response factor FOXO3 is neuroprotective in models of Huntington's disease (HD), Parkinson's disease and motor-neuron diseases. Neuroprotective compounds acting in a FOXO-dependent manner could thus constitute bona fide drugs for promoting neuronal compensation. However, whether FOXO-dependent neuroprotection is a common feature of several compound families remains unknown...
June 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28612944/the-skn-1-nrf2-transcription-factor-can-protect-against-oxidative-stress-and-increase-lifespan-in-c-%C3%A2-elegans-by-distinct-mechanisms
#12
Jennifer M A Tullet, James W Green, Catherine Au, Alexandre Benedetto, Maximillian A Thompson, Emily Clark, Ann F Gilliat, Adelaide Young, Kathrin Schmeisser, David Gems
In C. elegans, the skn-1 gene encodes a transcription factor that resembles mammalian Nrf2 and activates a detoxification response. skn-1 promotes resistance to oxidative stress (Oxr) and also increases lifespan, and it has been suggested that the former causes the latter, consistent with the theory that oxidative damage causes aging. Here, we report that effects of SKN-1 on Oxr and longevity can be dissociated. We also establish that skn-1 expression can be activated by the DAF-16/FoxO transcription factor, another central regulator of growth, metabolism, and aging...
June 14, 2017: Aging Cell
https://www.readbyqxmd.com/read/28576866/heat-induced-calcium-leakage-causes-mitochondrial-damage-in-caenorhabditis-elegans-body-wall-muscles
#13
Kenta Momma, Takashi Homma, Ruri Isaka, Surabhi Sudevan, Atsushi Higashitani
Acute onset of organ failure in heatstroke is triggered by rhabdomyolysis of skeletal muscle. To gain insight into heat-induced muscle breakdown, we investigated alterations of Ca(2+) homeostasis and mitochondrial morphology in vivo in body-wall muscles of Caenorhabditis elegans exposed to elevated temperature. Heat stress for 3h at 35°C increased the concentration of free cytosolic Ca(2+), and led to mitochondrial fragmentation and subsequent dysfunction in the muscle cells. A similar mitochondrial fragmentation phenotype is induced in the absence of heat stress by treatment with a calcium ionophore, ionomycin...
June 1, 2017: Genetics
https://www.readbyqxmd.com/read/28571752/insights-into-the-differential-toxicological-and-antioxidant-effects-of-4-phenylchalcogenil-7-chloroquinolines-in-caenorhabditis-elegans
#14
Willian G Salgueiro, Bruna S Goldani, Tanara V Peres, Antonio Miranda-Vizuete, Michael Aschner, João Batista Teixeira da Rocha, Diego Alves, Daiana S Ávila
Organic selenium and tellurium compounds are known for their broad-spectrum effects in a variety of experimental disease models. However, these compounds commonly display high toxicity and the molecular mechanisms underlying these deleterious effects have yet to be elucidated. Thus, the need for an animal model that is inexpensive, amenable to high-throughput analyses, and feasible for molecular studies is highly desirable to improve organochalcogen pharmacological and toxicological characterization. Herein, we use Caenorhabdtis elegans (C...
May 30, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28562327/the-protein-kinase-mbk-1-contributes-to-lifespan-extension-in-daf-2-mutant-and-germline-deficient-caenorhabditis-elegans
#15
Hildegard I D Mack, Peichuan Zhang, Bryan R Fonslow, John R Yates
In Caenorhabditis elegans, reduction of insulin/IGF-1 like signaling and loss of germline stem cells both increase lifespan by activating the conserved transcription factor DAF-16 (FOXO). While the mechanisms that regulate DAF-16 nuclear localization in response to insulin/IGF-1 like signaling are well characterized, the molecular pathways that act in parallel to regulate DAF-16 transcriptional activity, and the pathways that couple DAF-16 activity to germline status, are not fully understood at present. Here, we report that inactivation of MBK-1, the C...
May 25, 2017: Aging
https://www.readbyqxmd.com/read/28557996/the-cell-non-autonomous-function-of-atg-18-is-essential-for-neuroendocrine-regulation-of-caenorhabditis-elegans-lifespan
#16
Justin Minnerly, Jiuli Zhang, Thomas Parker, Tiffany Kaul, Kailiang Jia
Dietary restriction (DR) and reduced insulin growth factor (IGF) signaling extend lifespan in Caenorhabditis elegans and other eukaryotic organisms. Autophagy, an evolutionarily conserved lysosomal degradation pathway, has emerged as a central pathway regulated by various longevity signals including DR and IGF signaling in promoting longevity in a variety of eukaryotic organisms. However, the mechanism remains unclear. Here we show that the autophagy protein ATG-18 acts cell non-autonomously in neuronal and intestinal tissues to maintain C...
May 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28549065/c-elegans-daf-16-foxo-interacts-with-tgf-%C3%A3-bmp-signaling-to-induce-germline-tumor-formation-via-mtorc1-activation
#17
Wenjing Qi, Yijian Yan, Dietmar Pfeifer, Erika Donner V Gromoff, Yimin Wang, Wolfgang Maier, Ralf Baumeister
Activation of the FOXO transcription factor DAF-16 by reduced insulin/IGF signaling (IIS) is considered to be beneficial in C. elegans due to its ability to extend lifespan and to enhance stress resistance. In the germline, cell-autonomous DAF-16 activity prevents stem cell proliferation, thus acting tumor-suppressive. In contrast, hypodermal DAF-16 causes a tumorous germline phenotype characterized by hyperproliferation of the germline stem cells and rupture of the adjacent basement membrane. Here we show that cross-talk between DAF-16 and the transforming growth factor ß (TGFß)/bone morphogenic protein (BMP) signaling pathway causes germline hyperplasia and results in disruption of the basement membrane...
May 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28533928/leucine-nicotinic-acid-synergy-stimulates-ampk-sirt1-signaling-and-regulates-lipid-metabolism-and-lifespan-in-caenorhabditis-elegans-and-hyperlipidemia-and-atherosclerosis-in-mice
#18
Antje Bruckbauer, Jheelam Banerjee, Quiang Cao, Xin Cui, Jia Jing, Lin Zha, Fenfen Li, Bingzhong Xue, Hang Shi, Michael B Zemel
BACKGROUND/AIMS: Nicotinic acid (NA), a lipid-lowering drug, serves as a source of NAD(+), the cofactor for Sirt1. Leucine (Leu) stimulates the AMPK/Sirt1 axis and amplifies the effects of other AMPK/Sirt1 activating compounds. Therefore, we tested the interactive effects of leucine and low dose NA on AMPK/Sirt1 signaling and downstream effects of lipid metabolism in cell culture, C. elegans and mice. METHODS: LDL-receptor knockout mice were fed an atherogenic Western diet supplemented with leucine (24 g/kg diet) and sub-therapeutic NA combinations (50 mg/kg diet and 250 mg/kg diet) or low therapeutic NA (1000 mg/kg diet) for 8 weeks to evaluate markers of hyperlipidemia and atherosclerosis...
2017: American Journal of Cardiovascular Disease
https://www.readbyqxmd.com/read/28507100/the-microrna-machinery-regulates-fasting-induced-changes-in-gene-expression-and-longevity-in-caenorhabditis-elegans
#19
Akiko Kogure, Masaharu Uno, Takako Ikeda, Eisuke Nishida
Intermittent fasting (IF) is a dietary restriction regimen that extends the lifespans of Caenorhabditis elegans and mammals by inducing changes in gene expression. However, how IF induces these changes and promotes longevity remains unclear. One proposed mechanism involves gene regulation by microRNAs (miRNAs), small non-coding RNAs (∼22 nucleotides) that repress gene expression and whose expression can be altered by fasting. To test this proposition, we examined the role of the miRNA machinery in fasting-induced transcriptional changes and longevity in C...
July 7, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28505088/1-4-naphthoquinone-triggers-nematode-lethality-by-inducing-oxidative-stress-and-activating-insulin-igf-signaling-pathway-in-caenorhabditis-elegans
#20
Jia Wang, Guangzhi Zeng, Xiaobing Huang, Zhe Wang, Ninghua Tan
Plant-parasitic nematodes are destructive pathogens causing enormous economic losses worldwide. With the withdrawal of fumigants, organophosphates and carbamates, pathogenic nematode control is more difficult. Phytochemicals are the plant secondary metabolites and are friendly for men and the environment. For developing new nematocidal candidates, we screened 790 phytochemicals using the model organism Caenorhabditis elegans and found 10 active compounds, 3 of which were further evaluated for their inhibitory activities against egg hatching of C...
May 13, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
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