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C elegans aging

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https://www.readbyqxmd.com/read/28220799/impact-of-genetic-background-and-experimental-reproducibility-on-identifying-chemical-compounds-with-robust-longevity-effects
#1
Mark Lucanic, W Todd Plummer, Esteban Chen, Jailynn Harke, Anna C Foulger, Brian Onken, Anna L Coleman-Hulbert, Kathleen J Dumas, Suzhen Guo, Erik Johnson, Dipa Bhaumik, Jian Xue, Anna B Crist, Michael P Presley, Girish Harinath, Christine A Sedore, Manish Chamoli, Shaunak Kamat, Michelle K Chen, Suzanne Angeli, Christina Chang, John H Willis, Daniel Edgar, Mary Anne Royal, Elizabeth A Chao, Shobhna Patel, Theo Garrett, Carolina Ibanez-Ventoso, June Hope, Jason L Kish, Max Guo, Gordon J Lithgow, Monica Driscoll, Patrick C Phillips
Limiting the debilitating consequences of ageing is a major medical challenge of our time. Robust pharmacological interventions that promote healthy ageing across diverse genetic backgrounds may engage conserved longevity pathways. Here we report results from the Caenorhabditis Intervention Testing Program in assessing longevity variation across 22 Caenorhabditis strains spanning 3 species, using multiple replicates collected across three independent laboratories. Reproducibility between test sites is high, whereas individual trial reproducibility is relatively low...
February 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28198373/hormetic-heat-stress-and-hsf-1-induce-autophagy-to-improve-survival-and-proteostasis-in-c-elegans
#2
Caroline Kumsta, Jessica T Chang, Jessica Schmalz, Malene Hansen
Stress-response pathways have evolved to maintain cellular homeostasis and to ensure the survival of organisms under changing environmental conditions. Whereas severe stress is detrimental, mild stress can be beneficial for health and survival, known as hormesis. Although the universally conserved heat-shock response regulated by transcription factor HSF-1 has been implicated as an effector mechanism, the role and possible interplay with other cellular processes, such as autophagy, remains poorly understood...
February 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28196094/innate-immunity-mediated-longevity-and-longevity-induced-by-germ-cell-removal-converge-on-the-c-type-lectin-domain-protein-irg-7
#3
Elad Yunger, Modi Safra, Mor Levi-Ferber, Anat Haviv-Chesner, Sivan Henis-Korenblit
In C. elegans, removal of the germline triggers molecular events in the neighboring intestine, which sends an anti-aging signal to the rest of the animal. In this study, we identified an innate immunity related gene, named irg-7, as a novel mediator of longevity in germlineless animals. We consider irg-7 to be an integral downstream component of the germline longevity pathway because its expression increases upon germ cell removal and its depletion interferes with the activation of the longevity-promoting transcription factors DAF-16 and DAF-12 in germlineless animals...
February 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28194725/otophylloside-b-protects-against-a%C3%AE-toxicity-in-caenorhabditis-elegans-models-of-alzheimer-s-disease
#4
Jie Yang, Xiao-Bing Huang, Qin-Li Wan, Ai-Jun Ding, Zhong-Lin Yang, Ming-Hua Qiu, Hua-Ying Sun, Shu-Hua Qi, Huai-Rong Luo
Alzheimer's disease (AD) is a major public health concern worldwide and the few drugs currently available only treat the symptoms. Hence, there is a strong need to find more effective anti-AD agents. Cynanchum otophyllum is a traditional Chinese medicine for treating epilepsy, and otophylloside B (Ot B), isolated from C. otophyllum, is the essential active component. Having previously identified anti-aging effects of Ot B, we evaluated Ot B for AD prevention in C. elegans models of AD and found that Ot B extended lifespan, increased heat stress-resistance, delayed body paralysis, and increased the chemotaxis response...
February 13, 2017: Natural Products and Bioprospecting
https://www.readbyqxmd.com/read/28178240/c-elegans-neurons-jettison-protein-aggregates-and-mitochondria-under-neurotoxic-stress
#5
Ilija Melentijevic, Marton L Toth, Meghan L Arnold, Ryan J Guasp, Girish Harinath, Ken C Nguyen, Daniel Taub, J Alex Parker, Christian Neri, Christopher V Gabel, David H Hall, Monica Driscoll
The toxicity of misfolded proteins and mitochondrial dysfunction are pivotal factors that promote age-associated functional neuronal decline and neurodegenerative disease. Accordingly, neurons invest considerable cellular resources in chaperones, protein degradation, autophagy and mitophagy to maintain proteostasis and mitochondrial quality. Complicating the challenges of neuroprotection, misfolded human disease proteins and mitochondria can move into neighbouring cells via unknown mechanisms, which may promote pathological spread...
February 8, 2017: Nature
https://www.readbyqxmd.com/read/28177875/metabolomic-signature-associated-with-reproduction-regulated-aging-in-caenorhabditis-elegans
#6
Qin-Li Wan, Xiaohuo Shi, Jiangxin Liu, Ai-Jun Ding, Yuan-Zhu Pu, Zhigang Li, Gui-Sheng Wu, Huai-Rong Luo
In Caenorhabditis elegans (C. elegans), ablation of germline stem cells (GSCs) leads to infertility, which extends lifespan. It has been reported that aging and reproduction are both inextricably associated with metabolism. However, few studies have investigated the roles of polar small molecules metabolism in regulating longevity by reproduction. In this work, we combined the nuclear magnetic resonance (NMR) and ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) to profile the water-soluble metabolome in C...
February 6, 2017: Aging
https://www.readbyqxmd.com/read/28155715/screening-lifespan-extending-drugs-in-caenorhabditis-elegans-via-label-propagation-on-drug-protein-networks
#7
Hui Liu, Mengmeng Guo, Ting Xue, Jihong Guan, Libo Luo, Ziheng Zhuang
BACKGROUND: One of the most challenging tasks in the exploration of anti-aging is to discover drugs that can promote longevity and delay the incidence of age-associated diseases of human. Up to date, a number of drugs, including some antioxidants, metabolites and synthetic compounds, have been found to effectively delay the aging of nematodes and insects. RESULTS: We proposed a label propagation algorithm on drug-protein network to infer drugs that can extend the lifespan of C...
December 23, 2016: BMC Systems Biology
https://www.readbyqxmd.com/read/28133928/n-%C3%AE-l-glutamyl-l-selenomethionine-enhances-stress-resistance-and-ameliorates-aging-indicators-via-the-selenoprotein-trxr-1-in-caenorhabditis-elegans
#8
Chun-Han Chang, Chi-Tang Ho, Vivian Hsiu-Chuan Liao
SCOPE: Selenium is an essential trace nutrient for human health. This study investigates the organic form of selenium, N-γ-(L-Glutamyl)-L-selenomethionine (Glu-SeMet), for its effects on aging indicators and stress resistance. The role of the selenoprotein TRXR-1 was also evaluated in Caenorhabditis elegans. METHODS AND RESULTS: Glu-SeMet-treated wild-type N2 worms showed increased survival upon oxidative and thermal stress challenges. However, Glu-SeMet treatment did not extend the lifespan of wild-type N2 C...
January 29, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/28128482/piceatannol-extends-the-lifespan-of-caenorhabditis-elegans-via-daf-16
#9
Peiyi Shen, Yiren Yue, Quancai Sun, Nandita Kasireddy, Kee-Hong Kim, Yeonhwa Park
Piceatannol is a natural stilbene with many beneficial effects, such as antioxidative, anti-inflammatory, antiatherogenic activities; however, its role on aging is not known. In this study, we used Caenorhabditis elegans as an animal model to study the effect of piceatannol on its lifespan and investigated the underlying mechanisms. The results showed that 50 and 100 µM piceatannol significantly extended the lifespan of C. elegans without altering the growth rate, worm size and progeny production. Piceatannol delayed the age-related decline of pumping rate and locomotive activity, and protected the worms from heat and oxidative stress...
January 27, 2017: BioFactors
https://www.readbyqxmd.com/read/28125727/myosin-storage-myopathy-in-c-elegans-and-human-cultured-muscle-cells
#10
Martin Dahl-Halvarsson, Malgorzata Pokrzywa, Manish Rauthan, Marc Pilon, Homa Tajsharghi
Myosin storage myopathy is a protein aggregate myopathy associated with the characteristic subsarcolemmal accumulation of myosin heavy chain in muscle fibers. Despite similar histological findings, the clinical severity and age of onset are highly variable, ranging from no weakness to severe impairment of ambulation, and usually childhood-onset to onset later in life. Mutations located in the distal end of the tail of slow/ß-cardiac myosin heavy chain are associated with myosin storage myopathy. Four missense mutations (L1793P, R1845W, E1883K and H1901L), two of which have been reported in several unrelated families, are located within or closed to the assembly competence domain...
2017: PloS One
https://www.readbyqxmd.com/read/28121014/membrane-ion-channels-and-receptors-in-animal-lifespan-modulation
#11
REVIEW
Yi Sheng, Lanlan Tang, Lijun Kang, Rui Xiao
Acting in the interfaces between environment and membrane compartments, membrane ion channels and receptors transduce various physical and chemical cues into downstream signaling events. Not surprisingly, these membrane proteins play essential roles in a wide range of cellular processes such as sensory perception, synaptic transmission, cellular growth and development, fate determination, and apoptosis. However, except insulin and insulin-like growth factor receptors, the functions of membrane receptors in animal lifespan modulation have not been well appreciated...
January 25, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28119113/quantitative-proteomics-analysis-of-caenorhabditis-elegans-upon-germ-cell-loss
#12
Yuan-Zhu Pu, Qin-Li Wan, Ai-Jun Ding, Huai-Rong Luo, Gui-Sheng Wu
: The abrogation of the germ cells in Caenorhabditis elegans (C. elegans) by either genetic means or cell ablation results in about 60% increase of longevity. Upon the inhibition of germline stem cell proliferation, certain signaling molecules inhibit the target of rapamycin (TOR), activate the transcription factors including DAF-16, DAF-12, and PHA-4, leading to altered fatty acid lipolysis, autophagy, stress resistance, and the extended lifespan. But the exact cascades and interactions of those signaling pathways are still obscure...
March 6, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28119052/rbti-reduced-%C3%AE-amyloid-induced-toxicity-by-promoting-autophagy-lysosomal-degradation-via-daf-16-in-caenorhabditis-elegans
#13
Jiao Li, Xiaodong Cui, Xiaoli Ma, Zhuanhua Wang
Alzheimer's disease (AD) is an age-related neurodegenerative disease, of which β-amyloid (Aβ) induced toxicity was suggested as a main cause. Some substances with prolongevity effects have been shown to be protective against AD. In a previous study we demonstrated that a recombinant buckwheat trypsin inhibitor (rBTI) could prolonge the lifespan in Caenorhabditis elegans (C. elegans). Here, we investigated whether rBTI may benefit to mitigate the AD symptom by feeding the AD model C. elegans CL4176. CL4176 is a transgenic C...
January 21, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28117661/sexually-dimorphic-control-of-gene-expression-in-sensory-neurons-regulates-decision-making-behavior-in-c-elegans
#14
Zoë A Hilbert, Dennis H Kim
Animal behavior is directed by the integration of sensory information from internal states and the environment. Neuroendocrine regulation of diverse behaviors of Caenorhabditis elegans is under the control of the DAF-7/TGF-β ligand that is secreted from sensory neurons. Here, we show that C. elegans males exhibit an altered, male-specific expression pattern of daf-7 in the ASJ sensory neuron pair with the onset of reproductive maturity, which functions to promote male-specific mate-searching behavior. Molecular genetic analysis of the switch-like regulation of daf-7 expression in the ASJ neuron pair reveals a hierarchy of regulation among multiple inputs-sex, age, nutritional status, and microbial environment-which function in the modulation of behavior...
January 24, 2017: ELife
https://www.readbyqxmd.com/read/28109444/monitoring-protein-synthesis-in-caenorhabditis-elegans-using-silac
#15
M Miyagi
The static levels of proteins are the net results of their production and clearance regulated by the activities of proteins involved in their synthesis, degradation, and transportation. Therefore, the information on the rates of protein synthesis and clearance is needed to understand the underlying dynamic nature of a proteome. In this chapter, the experimental technique, we use in our laboratory for monitoring the synthesis of individual proteins in Caenorhabditis elegans (C. elegans) is described. The technique utilizes a preisotopically labeled amino acid ((13)C6-Lys) as a precursor for protein synthesis and monitors the kinetics of the precursor incorporation into the newly synthesized proteins...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28107363/age-dependent-neuroendocrine-signaling-from-sensory-neurons-modulates-the-effect-of-dietary-restriction-on-longevity-of-caenorhabditis-elegans
#16
Marissa Fletcher, Dennis H Kim
Dietary restriction extends lifespan in evolutionarily diverse animals. A role for the sensory nervous system in dietary restriction has been established in Drosophila and Caenorhabditis elegans, but little is known about how neuroendocrine signals influence the effects of dietary restriction on longevity. Here, we show that DAF-7/TGFβ, which is secreted from the C. elegans amphid, promotes lifespan extension in response to dietary restriction in C. elegans. DAF-7 produced by the ASI pair of sensory neurons acts on DAF-1/TGFβ receptors expressed on interneurons to inhibit the co-SMAD DAF-3...
January 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28093294/strehler-mildvan-correlation-is-a-degenerate-manifold-of-gompertz-fit
#17
Andrei E Tarkhov, Leonid I Menshikov, Peter O Fedichev
Gompertz empirical law of mortality is often used in practical research to parametrize survival fraction as a function of age with the help of just two quantities: the Initial Mortality Rate (IMR) and the Gompertz exponent, inversely proportional to the Mortality Rate Doubling Time (MRDT). The IMR is often found to be inversely related to the Gompertz exponent, which is the dependence commonly referred to as Strehler-Mildvan (SM) correlation. In this paper, we address fundamental uncertainties of the Gompertz parameters inference from experimental Kaplan-Meier plots and show, that a least squares fit often leads to an ill-defined non-linear optimization problem, which is extremely sensitive to sampling errors and the smallest systematic demographic variations...
January 16, 2017: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/28076789/reduced-insulin-igf-1-signaling-restores-the-dynamic-properties-of-key-stress-granule-proteins-during-aging
#18
Marie C Lechler, Emily D Crawford, Nicole Groh, Katja Widmaier, Raimund Jung, Janine Kirstein, Jonathan C Trinidad, Alma L Burlingame, Della C David
Low-complexity "prion-like" domains in key RNA-binding proteins (RBPs) mediate the reversible assembly of RNA granules. Individual RBPs harboring these domains have been linked to specific neurodegenerative diseases. Although their aggregation in neurodegeneration has been extensively characterized, it remains unknown how the process of aging disturbs RBP dynamics. We show that a wide variety of RNA granule components, including stress granule proteins, become highly insoluble with age in C. elegans and that reduced insulin/insulin-like growth factor 1 (IGF-1) daf-2 receptor signaling efficiently prevents their aggregation...
January 10, 2017: Cell Reports
https://www.readbyqxmd.com/read/28076775/nutritional-programming-of-lifespan-by-foxo-inhibition-on-sugar-rich-diets
#19
Adam J Dobson, Marina Ezcurra, Charlotte E Flanagan, Adam C Summerfield, Matthew D W Piper, David Gems, Nazif Alic
Consumption of unhealthy diets is exacerbating the burden of age-related ill health in aging populations. Such diets can program mammalian physiology to cause long-term, detrimental effects. Here, we show that, in Drosophila melanogaster, an unhealthy, high-sugar diet in early adulthood programs lifespan to curtail later-life survival despite subsequent dietary improvement. Excess dietary sugar promotes insulin-like signaling, inhibits dFOXO-the Drosophila homolog of forkhead box O (FOXO) transcription factors-and represses expression of dFOXO target genes encoding epigenetic regulators...
January 10, 2017: Cell Reports
https://www.readbyqxmd.com/read/28039571/identification-of-a-previously-undetected-metabolic-defect-in-the-complex-ii-caenorhabditis-elegans-mev-1-mutant-strain-using-respiratory-control-analysis
#20
Sheng Fong, Li Fang Ng, Li Theng Ng, Philip K Moore, Barry Halliwell, Jan Gruber
Hypometabolism may play an important role in the pathogenesis of ageing and ageing-related diseases. The nematode Caenorhabditis elegans offers the opportunity to study "living mitochondria" in a small (~1 mm) animal replete with a highly stereotypical, yet complex, anatomy and physiology. Basal oxygen consumption rate is often employed as a proxy for energy metabolism in this context. This parameter is traditionally measured using single-chamber Clark electrodes without the addition of metabolic modulators...
December 30, 2016: Biogerontology
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