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C elegans aging

Lucie Sauzéat, Anne Laurençon, Vincent Balter
Ageing is accompanied by important chemical deregulations resulting in bodily metal imbalances. The way and extent to which these deregulations are associated with ageing processes are however poorly understood and their use as potential biomarkers of ageing has not been investigated. In this study, we report whole-body elementary concentrations and copper and zinc isotopic compositions of Caenorhabditis elegans in ageing wild type (i.e. 'normal'-lived) and mutant (i.e. short and long-lived) strains. We show that the strains are characterized by different levels of mutation-related variations such as in phosphorus and magnesium as well as in zinc isotopic composition...
March 14, 2018: Metallomics: Integrated Biometal Science
Yujuan Li, Shuwen Guan, Cong Liu, Xinhua Chen, Yuemei Zhu, Yutong Xie, Jianbin Wang, Xue Ji, Liqin Li, Zhuohan Li, Yue Zhang, Xiangzhi Zeng, Mingquan Li
This study aims to investigate the neuroprotective effects of Coptis chinensis Franch polysaccharide (CCP) on Aβ1-42 transgenic CL4176 Caenorhabditis elegans, as well as its mechanism of action. The results in life span experiment showed that CCP could significantly increase the lifespan of C. elegans and the effect is in the descending order of 100 mg/L > 500 mg/L > 200 mg/L. The behavioral experiments also demonstrated that CCP at the concentration of 100 mg/L could delay the paralysis rate of C...
March 7, 2018: International Journal of Biological Macromolecules
Aristeidis P Sfakianos, Laura E Mellor, Yoke Fei Pang, Paraskevi Kritsiligkou, Hope Needs, Hussein Abou-Hamdan, Laurent Désaubry, Gino B Poulin, Mark P Ashe, Alan J Whitmarsh
Stress granules are cytoplasmic mRNA-protein complexes that form upon the inhibition of translation initiation and promote cell survival in response to environmental insults. However, they are often associated with pathologies, including neurodegeneration and cancer, and changes in their dynamics are implicated in ageing. Here we show that the mTOR effector kinases S6 kinase 1 (S6K1) and S6 kinase 2 (S6K2) localise to stress granules in human cells and are required for their assembly and maintenance after mild oxidative stress...
March 9, 2018: Cell Death and Differentiation
Ata Ghavidel, Kunal Baxi, Martin Prusinkiewicz, Cynthia Swan, Zach R Belak, Christopher H Eskiw, Carlos E Carvalho, Troy A Harkness
The yeast, Saccharomyces cerevisiae , like other higher eukaryotes, undergo a finite number of cell divisions before exiting the cell cycle due to the effects of aging. Here, we show that yeast aging begins with the nuclear exclusion of Hcm1 in young cells, resulting in loss of acidic vacuoles. Autophagy is required for healthy aging in yeast, with proteins targeted for turnover by autophagy directed to the vacuole. Consistent with this, vacuolar acidity is necessary for vacuolar function and yeast longevity...
March 8, 2018: G3: Genes—Genomes—Genetics
Yujie Li, Sandra Finkbeiner, Athina Ganner, Julia Gerber, Marinella Klein, Manuel Grafe, Jakob Kandzia, Antje Thien, Kathrin Thedieck, Gerhard Breves, Thomas Jank, Ralf Baumeister, Gerd Walz, Elke Neumann-Haefelin
The mechanistic target of rapamycin (mTOR) kinase is central to metabolism and growth, and has a conserved role in aging. mTOR functions in two complexes, mTORC1 and mTORC2. In diverse eukaryotes, inhibition of mTORC1 signaling increases lifespan. mTORC1 transduces anabolic signals to stimulate protein synthesis and inhibits autophagy. In this study, we demonstrate that CGEF-1, the C. elegans homolog of the human guanine nucleotide exchange factor Dbl, is a novel binding partner of RHEB-1 and activator of mTORC1 signaling in C...
February 9, 2018: Oncotarget
Yonghak Seo, Samuel Kingsley, Griffin Walker, Michelle A Mondoux, Heidi A Tissenbaum
As Western diets continue to include an ever-increasing amount of sugar, there has been a rise in obesity and type 2 diabetes. To avoid metabolic diseases, the body must maintain proper metabolism, even on a high-sugar diet. In both humans and Caenorhabditis elegans , excess sugar (glucose) is stored as glycogen. Here, we find that animals increased stored glycogen as they aged, whereas even young adult animals had increased stored glycogen on a high-sugar diet. Decreasing the amount of glycogen storage by modulating the C...
March 6, 2018: Proceedings of the National Academy of Sciences of the United States of America
Herbenya Peixoto, Mariana Roxo, Hector Koolen, Felipe da Silva, Emerson Silva, Markus Santhosh Braun, Xiaojuan Wang, Michael Wink
The tree popularly known in Brazil as mulateiro or pau-mulato ( Calycophyllum spruceanum (Benth.) K. Schum.) is deeply embedded in the herbal medicine of the Amazon region. Different preparations of the bark are claimed to have anti-aging, antioxidant, antimicrobial, emollient, wound healing, hemostatic, contraceptive, stimulant, and anti-diabetic properties. The current study aims to provide the first step towards a science-based evidence of the beneficial effects of C. spruceanum in the promotion of longevity and in the modulation of age-related markers...
February 27, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Bi Zhang, Jianke Gong, Wenyuan Zhang, Rui Xiao, Jianfeng Liu, X Z Shawn Xu
Tissue-tissue communications are integral to organismal aging, orchestrating a body-wide aging process. The brain plays a key role in this process by detecting and processing signals from the environment and then communicating them to distal tissues such as the gut to regulate longevity. How this is achieved, however, is poorly understood. Here, using Caenorhabditis elegans as a model, we identified two distinct neuroendocrine signaling circuits by which the worm nervous system senses cool and warm environmental temperatures through cool- and warm-sensitive neurons and then signals the gut to extend and shorten life span, respectively...
February 1, 2018: Genes & Development
Stijn Mouton, Magda Grudniewska, Lisa Glazenburg, Victor Guryev, Eugene Berezikov
Animals show a large variability of lifespan, ranging from short-lived as Caenorhabditis elegans to immortal as Hydra. A fascinating case is flatworms, in which reversal of aging by regeneration is proposed, yet conclusive evidence for this rejuvenation-by-regeneration hypothesis is lacking. We tested this hypothesis by inducing regeneration in the sexual free-living flatworm Macrostomum lignano. We studied survival, fertility, morphology, and gene expression as a function of age. Here, we report that after regeneration, genes expressed in the germline are upregulated at all ages, but no signs of rejuvenation are observed...
February 28, 2018: Aging Cell
Jason F Cooper, Jeremy M Van Raamsdonk
Parkinson's disease (PD) is an adult onset neurodegenerative disease that is characterized by selective degeneration of neurons primarily in the substantia nigra. At present, the pathogenesis of PD is incompletely understood and there are no neuroprotective treatments available. Accurate animal models of PD provide the opportunity to elucidate disease mechanisms and identify therapeutic targets. This review focuses on C. elegans models of PD, including both genetic and toxicant models. This microscopic worm offers several advantages for the study of PD including ease of genetic manipulation, ability to complete experiments rapidly, low cost, and ability to perform large scale screens for disease modifiers...
2018: Journal of Parkinson's Disease
Dhaval Patel, Chuan Xu, Sureshbabu Nagarajan, Zhengchang Liu, Wayne O Hemphill, Runhua Shi, Vladimir N Uversky, Guy A Caldwell, Kim A Caldwell, Stephan N Witt
We probed the role of alpha-synuclein (α-syn) in modulating sorting nexin 3 (Snx3)-retromer-mediated recycling of iron transporters in Saccharomyces cerevisiae and Caenorhabditis elegans. In yeast, the membrane-bound heterodimer Fet3/Ftr1 is the high affinity iron importer. Fet3 is a membrane-bound multicopper ferroxidase, whose ferroxidase domain is orthologous to human ceruloplasmin (Cp), that oxidizes external Fe+2 to Fe+3; the Fe+3 ions then channel through the Ftr1 permease into the cell. When the concentration of external iron is low (< 1 µM), Fet3/Ftr1 is maintained on the plasma membrane by retrograde endocytic-recycling; whereas, when the concentration of external iron is high (> 10 µM), Fet3/Ftr1 is endocytosed and shunted to the vacuole for degradation...
February 14, 2018: Human Molecular Genetics
Sudip Mondal, Evan Hegarty, James J Sahn, Luisa L Scott, Sertan K Gökçe, Christopher Martin, Navid Ghorashian, Praveen Navoda Satarasinghe, Sangeetha Iyer, Wisath Sae-Lee, Timothy Hodges, Jonathan T Pierce, Stephen F Martin, Adela Ben-Yakar
The nematode Caenorhabditis elegans, with tractable genetics and a well-defined nervous system, provides a unique whole-animal model system to identify novel drug targets and therapies for neurodegenerative diseases. Large-scale drug or target screens in models that recapitulate the subtle age- and cell-specific aspects of neurodegenerative diseases are limited by a technological requirement for high-throughput analysis of neuronal morphology. Recently we developed a model of amyloid precursor protein-induced neurodegeneration that exhibits progressive degeneration of select cholinergic neurons...
February 9, 2018: ACS Chemical Neuroscience
Christin Riedinger, Michael Mendler, Andrea Schlotterer, Thomas Fleming, Jürgen Okun, Hans-Peter Hammes, Stephan Herzig, Peter P Nawroth
The enzyme AICAR-transformylase/IMP cyclohydrolase (ATIC) catalyzes the last two steps of purine de-novo synthesis. It metabolizes AICAR, which is an AMP analogue, leading to activation of AMPK. It was investigated whether the AICAR-ATIC pathway plays a role in the high glucose (HG) mediated DNA damage response and AICAR mediated AMPK activation, explaining the detrimental effects of glucose on neuronal damages and shortening of lifespan. HG up-regulated the expression and activity of Caenorhabditis elegans homologue of ATIC, C55F2...
February 2, 2018: Journal of Biological Chemistry
Fang Li, Xiaoli Ma, Xiaodong Cui, Jiao Li, Zhuanhua Wang
Glutaredoxin (Grx) is a polypeptide with low molecular weight, which has been extracted from buckwheat and has been suggested to have multiple functions revolving around oxidative stress responses and cell signaling. Here, we report the antioxidant activity of recombinant buckwheat Grx (rbGrx) to reduce aging effects in Caenorhabditis elegans as well as the mechanism involved. Our results showed that rbGrx beneficially affected the health span of C. elegans, including pharyngeal-pumping rate, locomotion, and lipofuscin accumulation...
February 4, 2018: Experimental Gerontology
Lloyd Davis, Sebastian Greiss
Site-specific incorporation of unnatural amino acids (UAAs) has greatly expanded the toolkit available to study biological phenomena in single cells. However, to address questions involving complex cellular interactions such as development, ageing, and the functions of the nervous system it is often necessary to use multicellular model organisms. The nematode Caenorhabditis elegans was the first organism to have its genetic code expanded. Due to its small size, ease of cultivation, and excellent UAA incorporation efficiency, C...
2018: Methods in Molecular Biology
Vivian Hsiu-Chuan Liao
There is growing need and interest in finding specific compounds in natural products that have health benefits. Despite ongoing efforts to discover such compounds, the scientific evidence lags behind the vision, and it is important to find an effective paradigm for discovering such compounds. The model organism Caenorhabditis elegans offers a promising solution for studying the potential bioactivity and molecular mechanisms of natural compounds in vivo. This perspective discusses its use to study potential human health benefits, with focus on antioxidative, anti-aging, antimetabolic disorders (diabetes and obesity), and antineurodegenerative activities (Alzheimer's disease and Parkinson's disease), with practical examples...
February 28, 2018: Journal of Agricultural and Food Chemistry
Hui-Fang Chiu, Su-Chun Hsiao, Yan-Ying Lu, Yi-Chun Han, You-Cheng Shen, Kamesh Venkatakrishnan, Chin-Kun Wang
Pearl is one of the well-known traditional Chinese medicine (TCM) prescribed for treating various skin and bone related disorders due to its abundant proteins and mineral contents. The present investigation focused on antioxidation and life span prolonging effects from different extracts of pearl powder. During in vitro studies, various oxidative indices were evaluated, along with lifespan-prolonging effect were checked using wild-type Caenorhabditis elegans. For the clinical trial, 20 healthy middle-aged subjects were recruited and separated into 2 groups as experimental and placebo group, who received 3 g of pearl powder/d (n = 10) and 3 g of placebo/d (n = 10) for 8 weeks, respectively...
January 2018: Journal of Food and Drug Analysis
Samuel Sofela, Sarah Sahloul, Mehdi Rafeie, Taehong Kwon, Jongyoon Han, Majid Ebrahimi Warkiani, Yong-Ak Song
In this study, we report the use of a high-throughput microfluidic spiral chip to screen out eggs from a mixed age nematode population, which can subsequently be cultured to a desired developmental stage. For the sorting of a mixture containing three different developmental stages, eggs, L1 and L4, we utilized a microfluidic spiral chip with a trapezoidal channel to obtain a sorting efficiency of above 97% and a sample purity (SP) of above 80% for eggs at different flow rates up to 10 mL min-1. The result demonstrated a cost-effective, simple, and highly efficient method for synchronizing C...
January 26, 2018: Lab on a Chip
Makiko Ueda, Tetsuya Sato, Yasuyuki Ohkawa, Yoshihiro H Inoue
MicroRNAs (miRNAs) are involved in the regulation of important biological processes. Here, we describe a novel Drosophila miRNAs involved in aging. We selected eight Drosophila miRNAs, displaying high homology with seed sequences of aging-related miRNAs characterized in other species, and investigated whether the over-expression of these miRNAs affected aging in Drosophila adult flies. The lifespan of adults over-expressing miR-305, a miRNA showing high homology with miR-239 in C. elegans, was significantly shorter...
January 5, 2018: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
Dong-Kyu Kim, Kyu-Won Cho, Woo Jung Ahn, Dayana Perez-Acuña, Hyunsu Jeong, He-Jin Lee, Seung-Jae Lee
Huntington disease (HD) is an inherited neurodegenerative disorder characterized by motor and cognitive dysfunction caused by expansion of polyglutamine (polyQ) repeat in exon 1 of huntingtin (HTT). In patients, the number of glutamine residues in polyQ tracts are over 35, and it is correlated with age of onset, severity, and disease progression. Expansion of polyQ increases the propensity for HTT protein aggregation, process known to be implicated in neurodegeneration. These pathological aggregates can be transmitted from neuron to another neuron, and this process may explain the pathological spreading of polyQ aggregates...
December 2017: Experimental Neurobiology
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