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https://www.readbyqxmd.com/read/27906968/structural-and-functional-recovery-of-sensory-cilia-in-c-elegans-ift-mutants-upon-aging
#1
Astrid Cornils, Ashish K Maurya, Lauren Tereshko, Julie Kennedy, Andrea G Brear, Veena Prahlad, Oliver E Blacque, Piali Sengupta
The majority of cilia are formed and maintained by the highly conserved process of intraflagellar transport (IFT). Mutations in IFT genes lead to ciliary structural defects and systemic disorders termed ciliopathies. Here we show that the severely truncated sensory cilia of hypomorphic IFT mutants in C. elegans transiently elongate during a discrete period of adult aging leading to markedly improved sensory behaviors. Age-dependent restoration of cilia morphology occurs in structurally diverse cilia types and requires IFT...
December 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27905558/microrna-mir-34-provides-robustness-to-environmental-stress-response-via-the-daf-16-network-in-c-elegans
#2
Meltem Isik, T Keith Blackwell, Eugene Berezikov
Diverse stresses and aging alter expression levels of microRNAs, suggesting a role for these posttranscriptional regulators of gene expression in stress modulation and longevity. Earlier studies demonstrated a central role for the miR-34 family in promoting cell cycle arrest and cell death following stress in human cells. However, the biological significance of this response was unclear. Here we show that in C. elegans mir-34 upregulation is necessary for developmental arrest, correct morphogenesis, and adaptation to a lower metabolic state to protect animals against stress-related damage...
December 1, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27896020/identification-of-phenolic-secondary-metabolites-from-schotia-brachypetala-sond-fabaceae-and-demonstration-of-their-antioxidant-activities-in-caenorhabditis-elegans
#3
Mansour Sobeh, Esraa ElHawary, Herbenya Peixoto, Rola M Labib, Heba Handoussa, Noha Swilam, Ahmed H El-Khatib, Farukh Sharapov, Tamer Mohamed, Sonja Krstin, Michael W Linscheid, Abdel Nasser Singab, Michael Wink, Nahla Ayoub
BACKGROUND: Schotia brachypetala Sond. (Fabaceae) is an endemic tree of Southern Africa whose phytochemistry and pharmacology were slightly studied. The present work aimed at profiling the major phenolics compounds present in the hydro-alcohol extract from S. brachypetala leaves (SBE) using LC/HRESI/MS/MS and NMR and prove their antioxidant capabilities using novel methods. METHODS: In vitro assays; DPPH, TEAC persulfate decolorizing kinetic and FRAP assays, and in vivo assays: Caenorhabditis elegans strains maintenance, Intracellular ROS in C...
2016: PeerJ
https://www.readbyqxmd.com/read/27882602/the-resveratrol-derivatives-trans-3-5-dimethoxy-4-fluoro-4-hydroxystilbene-and-trans-2-4-5-trihydroxystilbene-decrease-oxidative-stress-and-prolong-lifespan-in-caenorhabditis-elegans
#4
Nadine Fischer, Christian Büchter, Karoline Koch, Sabrina Albert, René Csuk, Wim Wätjen
OBJECTIVES: Resveratrol (trans-3,4',5-trihydroxystilbene (1)) was previously shown to extend the lifespan of different model organisms. However, its pharmacological efficiency is controversially discussed. Therefore, the bioactivity of four newly synthesized stilbenes (trans-3,5-dimethoxy-4-fluoro-4'-hydroxystilbene (3), trans-4'-hydroxy-3,4,5-trifluorostilbene (4), trans-2,5-dimethoxy-4'-hydroxystilbene (5), trans-2,4',5-trihydroxystilbene (6)) was compared to (1) and pterostilbene (trans-3,5-dimethoxy-4'-hydroxystilbene (2)) in the established model organism Caenorhabditis elegans...
November 23, 2016: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/27864060/fos-1-functions-as-a-transcriptional-activator-downstream-of-the-c-elegans-jnk-homolog-kgb-1
#5
Zhe Zhang, Limeng Liu, Kwame Twumasi-Boateng, Dena H S Block, Michael Shapira
JNK proteins are conserved stress-activated MAP kinases. In C. elegans, the JNK-homolog KGB-1 plays essential roles in protection from heavy metals and protein folding stress. However, the contributions of KGB-1 are age-dependent, providing protection in larvae, but reducing stress resistance and shortening lifespan in adults. Attenuation of DAF-16 was linked to the detrimental contributions of KGB-1 in adults, but its involvement in KGB-1-dependent protection in larvae remains unclear. To characterize age-dependent contributions of KGB-1, we used microarray analysis to measure gene expression following KGB-1 activation either in developing larvae or in adults, achieved by knocking down its negative phosphatase regulator vhp-1...
November 15, 2016: Cellular Signalling
https://www.readbyqxmd.com/read/27854075/benzimidazole-derivative-m084-extends-the-lifespan-of-caenorhabditis-elegans-in-a-daf-16-foxo-dependent-way
#6
Ai-Jun Ding, Gui-Sheng Wu, Bin Tang, Xuechuan Hong, Michael X Zhu, Huai-Rong Luo
With the growth of aging population, there is increasing demand to develop strategy to improve the aging process and aging-related diseases. Benzimidazole and its derivatives are crucial heterocyclic backbone of many drugs and compounds with diverse therapeutic applications, including alleviation of aging-related diseases. Here, we investigate if the benzimidazole derivative n-butyl-[1H]-benzimidazol-2-amine (M084), a novel inhibitor of TRPC4 and TRPC5 channels and antidepressant, could affect the lifespan of Caenorhabditis elegans (C...
November 16, 2016: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/27853905/an-antidiabetic-polyherbal-phytomedicine-confers-stress-resistance-and-extends-lifespan-in-caenorhabditis-elegans
#7
Laxmi Rathor, Aakanksha Pant, Harshika Awasthi, Dayanandan Mani, Rakesh Pandey
An Ayurvedic polyherbal extract (PHE) comprising six herbs viz. Berberis aristata, Cyperus rotundus, Cedrus deodara, Emblica officinalis, Terminalia chebula and Terminalia bellirica is mentioned as an effective anti-hyperglycemic agent in 'Charaka Samhita', the classical text of Ayurveda. Previously, antidiabetic drug metformin was found to elicit antiaging effects and PHE was also found to exhibit antidiabetic effects in humans. Therefore, we screened it for its in vivo antioxidant antiaging effect on stress and lifespan using human homologous Caenorhabditis elegans model system...
November 16, 2016: Biogerontology
https://www.readbyqxmd.com/read/27810910/the-lysosomal-membrane-protein-scav-3-maintains-lysosome-integrity-and-adult-longevity
#8
Yuan Li, Baohui Chen, Wei Zou, Xin Wang, Yanwei Wu, Dongfeng Zhao, Yanan Sun, Yubing Liu, Lianwan Chen, Long Miao, Chonglin Yang, Xiaochen Wang
Lysosomes degrade macromolecules and recycle metabolites as well as being involved in diverse processes that regulate cellular homeostasis. The lysosome is limited by a single phospholipid bilayer that forms a barrier to separate the potent luminal hydrolases from other cellular constituents, thus protecting the latter from unwanted degradation. The mechanisms that maintain lysosomal membrane integrity remain unknown. Here, we identified SCAV-3, the Caenorhabditis elegans homologue of human LIMP-2, as a key regulator of lysosome integrity, motility, and dynamics...
October 24, 2016: Journal of Cell Biology
https://www.readbyqxmd.com/read/27791111/foxo6-affects-plxna4-mediated-neuronal-migration-during-mouse-cortical-development
#9
Ricardo H Paap, Saskia Oosterbroek, Cindy M R J Wagemans, Lars von Oerthel, Raymond D Schellevis, Annemarie J A Vastenhouw-van der Linden, Marian J A Groot Koerkamp, Marco F M Hoekman, Marten P Smidt
The forkhead transcription factor FoxO6 is prominently expressed during development of the murine neocortex. However, its function in cortical development is as yet unknown. We now demonstrate that cortical development is altered in FoxO6(+/-) and FoxO6(-/-) mice, showing migrating neurons halted in the intermediate zone. Using a FoxO6-directed siRNA approach, we substantiate the requirement of FoxO6 for a correct radial migration in the developing neocortex. Subsequent genome-wide transcriptome analysis reveals altered expression of genes involved in cell adhesion, axon guidance, and gliogenesis upon silencing of FoxO6 We then show that FoxO6 binds to DAF-16-binding elements in the Plexin A4 (Plxna4) promoter region and affects Plxna4 expression...
October 24, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27783623/maternal-diet-and-insulin-like-signaling-control-intergenerational-plasticity-of-progeny-size-and-starvation-resistance
#10
Jonathan D Hibshman, Anthony Hung, L Ryan Baugh
Maternal effects of environmental conditions produce intergenerational phenotypic plasticity. Adaptive value of these effects depends on appropriate anticipation of environmental conditions in the next generation, and mismatch between conditions may contribute to disease. However, regulation of intergenerational plasticity is poorly understood. Dietary restriction (DR) delays aging but maternal effects have not been investigated. We demonstrate maternal effects of DR in the roundworm C. elegans. Worms cultured in DR produce fewer but larger progeny...
October 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27773573/a-caenorhabditis-elegans-model-elucidates-a-conserved-role-for-trpa1-nrf-signaling-in-reactive-%C3%AE-dicarbonyl-detoxification
#11
Jyotiska Chaudhuri, Neelanjan Bose, Jianke Gong, David Hall, Alexander Rifkind, Dipa Bhaumik, T Harshani Peiris, Manish Chamoli, Catherine H Le, Jianfeng Liu, Gordon J Lithgow, Arvind Ramanathan, X Z Shawn Xu, Pankaj Kapahi
Reactive α-dicarbonyls (α-DCs), like methylglyoxal (MGO), accumulate with age and have been implicated in aging and various age-associated pathologies, such as diabetic complications and neurodegenerative disorders like Alzheimer's and Parkinson's diseases. Evolutionarily conserved glyoxalases are responsible for α-DC detoxification; however, their core biochemical regulation has remained unclear. We have established a Caenorhabditis elegans model, based on an impaired glyoxalase (glod-4/GLO1), to broadly study α-DC-related stress...
November 21, 2016: Current Biology: CB
https://www.readbyqxmd.com/read/27730721/lin-28-balances-longevity-and-germline-stem-cell-number-in-caenorhabditis-elegans-through-let-7-akt-daf-16-axis
#12
Dan Wang, Lei Hou, Shuhei Nakamura, Ming Su, Fang Li, Weiyang Chen, Yizhen Yan, Christopher D Green, Di Chen, Hong Zhang, Adam Antebi, Jing-Dong J Han
The RNA-binding protein LIN-28 was first found to control developmental timing in Caenorhabditis elegans. Later, it was found to play important roles in pluripotency, metabolism, and cancer in mammals. Here we report that a low dosage of lin-28 enhanced stress tolerance and longevity, and reduced germline stem/progenitor cell number in C. elegans. The germline LIN-28-regulated microRNA let-7 was required for these effects by targeting akt-1/2 and decreasing their protein levels. AKT-1/2 and the downstream DAF-16 transcription factor were both required for the lifespan and germline stem cell effects of lin-28...
October 11, 2016: Aging Cell
https://www.readbyqxmd.com/read/27717342/impact-is-a-gcn2-inhibitor-that-limits-lifespan-in-caenorhabditis-elegans
#13
Rafael C Ferraz, Henrique Camara, Evandro A De-Souza, Silas Pinto, Ana Paula F Pinca, Richard C Silva, Vitor N Sato, Beatriz A Castilho, Marcelo A Mori
BACKGROUND: The General Control Nonderepressible 2 (GCN2) kinase is a conserved member of the integrated stress response (ISR) pathway that represses protein translation and helps cells to adapt to conditions of nutrient shortage. As such, GCN2 is required for longevity and stress resistance induced by dietary restriction (DR). IMPACT is an ancient protein that inhibits GCN2. RESULTS: Here, we tested whether IMPACT down-regulation mimics the effects of DR in C. elegans...
October 7, 2016: BMC Biology
https://www.readbyqxmd.com/read/27716821/correction-daf-16-and-tcer-1-facilitate-adaptation-to-germline-loss-by-restoring-lipid-homeostasis-and-repressing-reproductive-physiology-in-c-elegans
#14
Francis Raj Gandhi Amrit, Elizabeth Marie Steenkiste, Ramesh Ratnappan, Shaw-Wen Chen, T Brooke McClendon, Dennis Kostka, Judith Yanowitz, Carissa Perez Olsen, Arjumand Ghazi
[This corrects the article DOI: 10.1371/journal.pgen.1005788.].
October 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27704837/ages-rage-related-neurodegeneration-daf-16-as-a-mediator-insulin-as-an-ameliorant-and-c-elegans-as-an-expedient-research-model
#15
Adi Pinkas, Michael Aschner
Advanced glycation end-products (AGEs) are non-enzymatically glycated proteins, lipids and nucleic acids. These compounds both originate exogenously and are formed endogenously, and are associated, along with one of their receptors - RAGE, with a variety of pathologies and neurodegeneration. Some of their deleterious effects include affecting insulin signaling and FOXO-related pathways in both receptor-dependent and -independent manner. A potential ameliorating agent for these effects is insulin, which is being studied in several in vivo and in vitro models; one of these models is C...
October 5, 2016: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/27690135/mutations-in-nonessential-eif3k-and-eif3l-genes-confer-lifespan-extension-and-enhanced-resistance-to-er-stress-in-caenorhabditis-elegans
#16
Douglas J Cattie, Claire E Richardson, Kirthi C Reddy, Elan M Ness-Cohn, Rita Droste, Mary K Thompson, Wendy V Gilbert, Dennis H Kim
The translation initiation factor eIF3 is a multi-subunit protein complex that coordinates the assembly of the 43S pre-initiation complex in eukaryotes. Prior studies have demonstrated that not all subunits of eIF3 are essential for the initiation of translation, suggesting that some subunits may serve regulatory roles. Here, we show that loss-of-function mutations in the genes encoding the conserved eIF3k and eIF3l subunits of the translation initiation complex eIF3 result in a 40% extension in lifespan and enhanced resistance to endoplasmic reticulum (ER) stress in Caenorhabditis elegans...
September 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27668945/cell-cycle-controls-stress-response-and-longevity-in-c-elegans
#17
Matthias Dottermusch, Theresa Lakner, Tobias Peyman, Marinella Klein, Gerd Walz, Elke Neumann-Haefelin
Recent studies have revealed a variety of genes and mechanisms that influence the rate of aging progression. In this study, we identified cell cycle factors as potent regulators of health and longevity in C. elegans. Focusing on the cyclin-dependent kinase 2 (cdk-2) and cyclin E (cye-1), we show that inhibition of cell cycle genes leads to tolerance towards environmental stress and longevity. The reproductive system is known as a key regulator of longevity in C. elegans. We uncovered the gonad as the central organ mediating the effects of cell cycle inhibition on lifespan...
September 25, 2016: Aging
https://www.readbyqxmd.com/read/27647012/antioxidant-and-neuroprotective-effects-of-dictyophora-indusiata-polysaccharide-in-caenorhabditis-elegans
#18
Ju Zhang, Ruona Shi, Haifeng Li, Yanxia Xiang, Lingyun Xiao, Minghua Hu, Fangli Ma, Chung Wah Ma, Zebo Huang
ETHNOPHARMACOLOGICAL RELEVANCE: Dictyophora indusiata is a medicinal mushroom traditionally used in China for a variety of conditions, including inflammatory and neural diseases. D. indusiata polysaccharides (DiPS) are shown to have in vitro antioxidant activity but in vivo evidence is lacking. This study aimes to explore the antioxidant capacity and related neuroptotective activities of DiPS using wild-type and neurodegenerative Caenorhabditis elegans models. MATERIALS AND METHODS: The antioxidant capacities of DiPS were first determined using paraquat survival and Pgst-4::GFP expression assays in wild-type and transgenic C...
November 4, 2016: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/27626670/foxo-daf-16-activation-slows-down-turnover-of-the-majority-of-proteins-in-c-%C3%A2-elegans
#19
Ineke Dhondt, Vladislav A Petyuk, Huaihan Cai, Lieselot Vandemeulebroucke, Andy Vierstraete, Richard D Smith, Geert Depuydt, Bart P Braeckman
Most aging hypotheses assume the accumulation of damage, resulting in gradual physiological decline and, ultimately, death. Avoiding protein damage accumulation by enhanced turnover should slow down the aging process and extend the lifespan. However, lowering translational efficiency extends rather than shortens the lifespan in C. elegans. We studied turnover of individual proteins in the long-lived daf-2 mutant by combining SILeNCe (stable isotope labeling by nitrogen in Caenorhabditiselegans) and mass spectrometry...
September 13, 2016: Cell Reports
https://www.readbyqxmd.com/read/27623524/an-intestinal-microrna-modulates-the-homeostatic-adaptation-to-chronic-oxidative-stress-in-c-elegans
#20
Masaomi Kato, Mohammed Abul Kashem, Chao Cheng
Adaptation to an environmental or metabolic perturbation is a feature of the evolutionary process. Recent insights into microRNA function suggest that microRNAs serve as key players in a robust adaptive response against stress in animals through their capacity to fine-tune gene expression. However, it remains largely unclear how a microRNA-modulated downstream mechanism contributes to the process of homeostatic adaptation. Here we show that loss of an intestinally expressed microRNA gene, mir-60, in the nematode C...
September 12, 2016: Aging
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