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C elegans aging

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https://www.readbyqxmd.com/read/29786878/dietary-omega-3-fatty-acids-differentially-impact-acute-ethanol-responsive-behaviors-and-ethanol-consumption-in-dba-2j-versus-c57bl-6j-mice
#1
Jennifer T Wolstenholme, M Scott Bowers, Alexander B Pais, A Christian Pais, Ryan S Poland, Justin L Poklis, Andrew G Davies, Jill C Bettinger
BACKGROUND: Complex interactions between environmental and genetic factors influence the risk for developing alcohol use disorder (AUD) in humans. To date, studies of the impact of environment on AUD risk have primarily focused on psychological characteristics or on the effects of developmental exposure to ethanol. We recently observed that modifying levels of the long-chain ω-3 (LC ω-3) fatty acid, eicosapentaenoic acid (EPA), alters acute physiological responses to ethanol in C. elegans...
May 22, 2018: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/29776378/differential-induction-of-mutant-sod1-misfolding-and-aggregation-by-tau-and-%C3%AE-synuclein-pathology
#2
Michael C Pace, Guilian Xu, Susan Fromholt, John Howard, Benoit I Giasson, Jada Lewis, David R Borchelt
BACKGROUND: Prior studies in C. elegans demonstrated that the expression of aggregation-prone polyglutamine proteins in muscle wall cells compromised the folding of co-expressed temperature-sensitive proteins, prompting interest in whether the accumulation of a misfolded protein in pathologic features of human neurodegenerative disease burdens cellular proteostatic machinery in a manner that impairs the folding of other cellular proteins. METHODS: Mice expressing high levels of mutant forms of tau and α-synuclein (αSyn), which develop inclusion pathologies of the mutant protein in brain and spinal cord, were crossed to mice expressing low levels of mutant superoxide dismutase 1 fused to yellow fluorescent protein (G85R-SOD1:YFP) for aging and neuropathological evaluation...
May 18, 2018: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/29772745/tryptophan-containing-dual-neuroprotective-peptides-prolyl-endopeptidase-inhibition-and-caenorhabditis-elegans-protection-from-%C3%AE-amyloid-peptide-toxicity
#3
Paloma Manzanares, Roberto Martínez, Sandra Garrigues, Salvador Genovés, Daniel Ramón, Jose F Marcos, Patricia Martorell
Neuroprotective peptides represent an attractive pharmacological strategy for the prevention or treatment of age-related diseases, for which there are currently few effective therapies. Lactoferrin (LF)-derived peptides (PKHs) and a set of six rationally-designed tryptophan (W)-containing heptapeptides (PACEIs) were characterized as prolyl endopeptidase (PEP) inhibitors, and their effect on β-amyloid peptide (Aβ) toxicity in a Caenorhabditis elegans model of Alzheimer's disease (AD) was evaluated. Two LF-derived sequences, PKH8 and PKH11, sharing a W at the C-terminal end, and the six PACEI heptapeptides (PACEI48L to PACEI53L) exhibited significant in vitro PEP inhibition...
May 16, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29769649/organoruthenium-ii-complexes-ameliorates-oxidative-stress-and-impedes-the-age-associated-deterioration-in-caenorhabditis-elegans-through-jnk-1-daf-16-signalling
#4
G Devagi, A Mohankumar, G Shanmugam, S Nivitha, F Dallemer, P Kalaivani, P Sundararaj, R Prabhakaran
New ruthenium(II) complexes were synthesised and characterized by various spectro analytical techniques. The structure of the complexes 3 and 4 has been confirmed by X-ray crystallography. The complexes were subjected to study their anti-oxidant profile and were exhibited significantly greater in vitro DPPH radical scavenging activity than vitamin C. We found that complexes 1-4 confered tolerance to oxidative stress and extend the mean lifespan of mev-1 mutant worms and wild-type Caenorhabditis elegans. Further, mechanistic study and reporter gene expression analysis revealed that Ru(ƞ6 -p-cymene) complexes maintained the intracellular redox status and offers stress resistance through activating JNK-1/DAF-16 signaling axis and possibly by other antioxidant response pathway...
May 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29766797/anti-aging-and-anti-aggregation-properties-of-polyphenolic-compounds-in-c-elegans
#5
Nikoletta Papaevgeniou, Niki Chondrogianni
Polyphenols constitute a group of compounds that have been highly investigated for their beneficial effects against various pathologic and non-pathologic conditions and diseases. Among their multi-faceted properties, their anti-oxidant potential nominates them as ideal protective candidates for conditions characterized by elevated levels of oxidative stress, including aging and age-related diseases. The nematode Caenorhabditis elegans is a multicellular model organism that is highly exploited in studies related to aging and age-associated diseases...
May 15, 2018: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/29763691/insights-on-the-age-dependent-neurodegeneration-induced-by-monocrotophos-an-organophosphorous-insecticide-in-caenorhabditis-elegans-fed-high-glucose-evidence-in-wild-and-transgenic-strains
#6
Chinnu Salim, Nidheesh Thadathil, M Muralidhara, P S Rajini
The higher susceptibility of high glucose fed C. elegans to Monocrotophos (MCP, an organophosphorus insecticide) - induced dopaminergic (DA) neuronal degeneration was recently demonstrated. Employing this acute exposure model, the impact of MCP on DA degeneration among worms of two age groups (8 and 13 d old) fed control (CO) and high glucose (GF) diet with specific focus on phenotypic alterations, oxidative impairments and associated molecular perturbations employing both wild (N2) and transgenic strains(BZ555 and NL5901) was investigated...
May 12, 2018: Comparative Biochemistry and Physiology. Toxicology & Pharmacology: CBP
https://www.readbyqxmd.com/read/29760342/1-2-3-triazolyl-ester-of-ketorolac-15k-boosting-both-heat-endurance-and-lifespan-of-c-elegans-by-down-regulating-pak1-at-nm-levels
#7
Binh C Nguyen, Sung-A Kim, Seong-Min Won, Sang-Kyu Park, Yoshihiro Uto, Hiroshi Maruta
PAK1 (RAC/CDC42-activated kinase 1) is the major oncogenic/ageing kinase, and its dysfunction extends the healthy lifespan of C. elegans by activating HSP16 gene. 15K is a highly cell-permeable 1,2,3-triazolyl ester of ketorolac that down-regulates both PAK1 and its down-stream COX-2 in R- and S-forms, respectively. 15K is 500-5,000 times more potent than ketorolac, an old pain-killer, inhibiting the growth of cancer cell lines with IC50 ranging 5-24 nM. Scores of natural and synthetic PAK1-blockers have been shown to extend the lifespan of small animals such as C...
2018: Drug Discoveries & Therapeutics
https://www.readbyqxmd.com/read/29760078/chaperone-ampylation-modulates-aggregation-and-toxicity-of-neurodegenerative-disease-associated-polypeptides
#8
Matthias C Truttmann, David Pincus, Hidde L Ploegh
Proteostasis is critical to maintain organismal viability, a process counteracted by aging-dependent protein aggregation. Chaperones of the heat shock protein (HSP) family help control proteostasis by reducing the burden of unfolded proteins. They also oversee the formation of protein aggregates. Here, we explore how AMPylation, a posttranslational protein modification that has emerged as a powerful modulator of HSP70 activity, influences the dynamics of protein aggregation. We find that adjustments of cellular AMPylation levels in Caenorhabditis elegans directly affect aggregation properties and associated toxicity of amyloid-β (Aβ), of a polyglutamine (polyQ)-extended polypeptide, and of α-synuclein (α-syn)...
May 14, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29748634/gene-by-environment-interactions-that-disrupt-mitochondrial-homeostasis-cause-neurodegeneration-in-c-elegans-parkinson-s-models
#9
Hanna Kim, Rylee J Perentis, Guy A Caldwell, Kim A Caldwell
Parkinson's disease (PD) is a complex multifactorial disorder where environmental factors interact with genetic susceptibility. Accumulating evidence suggests that mitochondria have a central role in the progression of neurodegeneration in sporadic and/or genetic forms of PD. We previously reported that exposure to a secondary metabolite from the soil bacterium, Streptomyces venezuelae, results in age- and dose-dependent dopaminergic (DA) neurodegeneration in Caenorhabditis elegans and human SH-SY5Y neurons...
May 10, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29709599/autophagy-in-c-elegans-development
#10
REVIEW
Nicholas J Palmisano, Alicia Meléndez
Autophagy involves the sequestration of cytoplasmic contents in a double-membrane structure referred to as the autophagosome and the degradation of its contents upon delivery to lysosomes. Autophagy activity has a role in multiple biological processes during the development of the nematode Caenorhabditis elegans. Basal levels of autophagy are required to remove aggregate prone proteins, paternal mitochondria, and spermatid-specific membranous organelles. During larval development, autophagy is required for the remodeling that occurs during dauer development, and autophagy can selectively degrade components of the miRNA-induced silencing complex, and modulate miRNA-mediated silencing...
April 27, 2018: Developmental Biology
https://www.readbyqxmd.com/read/29709515/5-methoxyindole-2-carboxylic-acid-mica-suppresses-a%C3%AE-mediated-pathology-in-c-elegans
#11
Waqar Ahmad, Paul R Ebert
Alzheimer's disease (AD) is an age-related disease characterized by loss of memory and disrupted thinking that is associated with altered energy metabolism. Variants of an important enzyme of energy metabolism, dihydrolipoamide dehydrogenase (dld), have been genetically linked to late-onset AD. Moreover, reduced activity of DLD-containing enzyme complexes is associated with AD progression. To understand how energy metabolism influences AD progression, we exposed C. elegans expressing human Aβ peptide to the chemical inhibitor of DLD, 2-methoxyindole-5-carboxylic acid (MICA)...
April 27, 2018: Experimental Gerontology
https://www.readbyqxmd.com/read/29708551/assessing-lysosomal-alkalinization-in-the-intestine-of-live-caenorhabditis-elegans
#12
Kunal Baxi, Carlos E de Carvalho
The nematode Caenorhabditis elegans (C. elegans) is a model system that is widely used to study longevity and developmental pathways. Such studies are facilitated by the transparency of the animal, the ability to do forward and reverse genetic assays, the relative ease of generating fluorescently labeled proteins, and the use of fluorescent dyes that can either be microinjected into the early embryo or incorporated into its food (E. coli strain OP50) to label cellular organelles (e.g. 9-diethylamino-5H-benzo(a)phenoxazine-5-one and (3-{2-[(1H,1'H-2,2'-bipyrrol-5-yl-kappaN(1))methylidene]-2H-pyrrol-5-yl-kappaN}-N-[2-(dimethylamino)ethyl]propanamidato)(difluoro)boron)...
April 13, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29670680/gengnianchun-extends-the-lifespan-of-caenorhabditis-elegans-via-the-insulin-igf-1-signalling-pathway
#13
Fanhui Meng, Jun Li, Yanqiu Rao, Wenjun Wang, Yan Fu
Gengnianchun (GNC), a traditional Chinese medicine (TCM), is believed to have beneficial effects on ageing-related diseases, such as antioxidant properties and effects against A β -induced toxicity. We previously found that GNC extended the lifespan of Caenorhabditis elegans . However, the mechanism underlying this effect was unclear. In this study, we further explored the mechanisms of GNC using a C. elegans model. GNC significantly increased the lifespan of C. elegans and enhanced oxidative and thermal stress resistance...
2018: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29656871/activation-of-g-%C3%AE-q-signaling-enhances-memory-consolidation-and-slows-cognitive-decline
#14
Rachel N Arey, Geneva M Stein, Rachel Kaletsky, Amanda Kauffman, Coleen T Murphy
Perhaps the most devastating decline with age is the loss of memory. Therefore, identifying mechanisms to restore memory function with age is critical. Using C. elegans associative learning and memory assays, we identified a gain-of-function Gαq signaling pathway mutant that forms a long-term (cAMP response element binding protein [CREB]-dependent) memory following one conditioned stimulus-unconditioned stimulus (CS-US) pairing, which usually requires seven CS-US pairings. Increased CREB activity in AIM interneurons reduces the threshold for memory consolidation through transcription of a set of previously identified "long-term memory" genes...
April 6, 2018: Neuron
https://www.readbyqxmd.com/read/29656019/proteomic-identification-of-virulence-related-factors-in-young-and-aging-c-elegans-infected-with-pseudomonas-aeruginosa
#15
Christina D King, Daljeet Singh, Kyle Holden, Annie B Govan, Scott A Keith, Arjumand Ghazi, Renã A S Robinson
The molecular mechanisms that distinguish immunosenescence from general age-related decline are poorly understood. We addressed this by exposing Day 1 and Day 5 adults of Caenorhabditis elegans to Pseudomonas aeruginosa strain PA01, an opportunistic pathogen. Day 5 adult C. elegans exhibited greater vulnerability to infection as compared to Day 1 C. elegans. Using TMT6 -plex isobaric labeling and reductive dimethylation, we identified 55 proteins whose levels were altered following infection of Day 1 and Day 5 adults...
April 12, 2018: Journal of Proteomics
https://www.readbyqxmd.com/read/29626130/the-gene-regulatory-program-of-acrobeloides-nanus-reveals-conservation-of-phylum-specific-expression
#16
Philipp H Schiffer, Avital L Polsky, Alison G Cole, Julia I R Camps, Michael Kroiher, David H Silver, Vladislav Grishkevich, Leon Anavy, Georgios Koutsovoulos, Tamar Hashimshony, Itai Yanai
The evolution of development has been studied through the lens of gene regulation by examining either closely related species or extremely distant animals of different phyla. In nematodes, detailed cell- and stage-specific expression analyses are focused on the model Caenorhabditis elegans , in part leading to the view that the developmental expression of gene cascades in this species is archetypic for the phylum. Here, we compared two species of an intermediate evolutionary distance: the nematodes C. elegans (clade V) and Acrobeloides nanus (clade IV)...
April 6, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29618610/roll-maneuvers-are-essential-for-active-reorientation-of-caenorhabditis-elegans-in-3d-media
#17
Alejandro Bilbao, Amar K Patel, Mizanur Rahman, Siva A Vanapalli, Jerzy Blawzdziewicz
Locomotion of the nematode Caenorhabditis elegans is a key observable used in investigations ranging from behavior to neuroscience to aging. However, while the natural environment of this model organism is 3D, quantitative investigations of its locomotion have been mostly limited to 2D motion. Here, we present a quantitative analysis of how the nematode reorients itself in 3D media. We identify a unique behavioral state of C. elegans -a roll maneuver-which is an essential component of 3D locomotion in burrowing and swimming...
April 4, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29615793/association-between-hypertension-and-circulating-vascular-related-micrornas
#18
Jamie G Hijmans, Kyle J Diehl, Tyler D Bammert, Philip J Kavlich, Grace M Lincenberg, Jared J Greiner, Brian L Stauffer, Christopher A DeSouza
microRNAs (miRNAs) have a key role in regulating inflammation, vascular health and in turn, cardiovascular disease. Specifically, altered circulating expression of miR-17, miR-21, miR-34a, miR-92a, miR-126, miR-145, miR-146a, and miR-150 has been linked with the pathogenesis and progression of cardiovascular disease. The aim of this study was to determine whether the circulating profile of these vascular-related miRNAs is disrupted with hypertension. Thirty sedentary, middle-aged adults were studied: 15 normotensive (10M/5F; age: 56 ± 1 year; BP: 113/71 ± 2/1 mmHg) and 15 hypertensive (10M/5F; 56 ± 2 year; 140/87 ± 2/2 mmHg)...
April 4, 2018: Journal of Human Hypertension
https://www.readbyqxmd.com/read/29607782/influence-of-overweight-and-obesity-on-circulating-inflammation-related-microrna
#19
Jamie G Hijmans, Kyle J Diehl, Tyler D Bammert, Philip J Kavlich, Grace M Lincenberg, Jared J Greiner, Brian L Stauffer, Christopher A DeSouza
BACKGROUND: Increased cardiovascular disease risk and prevalence associated with overweight and obesity is due, in part, to heightened inflammatory burden. The mechanisms underlying adiposity-related amplification of inflammation are not fully understood. Alterations in regulators of inflammatory processes such as microRNAs (miRs), however, is thought to play a pivotal role. OBJECTIVE: The aim of this study was to determine the influence of overweight and obesity, independent of other cardiovascular risk factors, on circulating expression of miR-34a, miR-126, miR-146a, miR-150 and miR-181b...
April 2, 2018: MicroRNA
https://www.readbyqxmd.com/read/29590100/glial-loss-of-the-metallo-%C3%AE-lactamase-domain-containing-protein-swip-10-induces-age-and-glutamate-signaling-dependent-dopamine-neuron-degeneration
#20
Chelsea L Gibson, Joseph T Balbona, Ashlin Niedzwiecki, Peter Rodriguez, Ken C Q Nguyen, David H Hall, Randy D Blakely
Across phylogeny, glutamate (Glu) signaling plays a critical role in regulating neural excitability, thus supporting many complex behaviors. Perturbed synaptic and extrasynaptic Glu homeostasis in the human brain has been implicated in multiple neuropsychiatric and neurodegenerative disorders including Parkinson's disease, where theories suggest that excitotoxic insults may accelerate a naturally occurring process of dopamine (DA) neuron degeneration. In C. elegans, mutation of the glial expressed gene, swip-10, results in Glu-dependent DA neuron hyperexcitation that leads to elevated DA release, triggering DA signaling-dependent motor paralysis...
March 28, 2018: PLoS Genetics
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