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C elegans aging

Michael Mendler, Christin Riedinger, Andrea Schlotterer, Nadine Volk, Thomas Fleming, Stephan Herzig, Peter P Nawroth, Michael Morcos
BACKGROUND: Glucose derived metabolism generates reactive metabolites affecting the neuronal system and lifespan in C. elegans. Here, the role of the insulin homologue ins-7 and its downstream effectors in the generation of high glucose induced neuronal damage and shortening of lifespan was studied. RESULTS: In C. elegans high glucose conditions induced the expression of the insulin homologue ins-7. Abrogating ins-7 under high glucose conditions in non-neuronal cells decreased reactive oxygen species (ROS)-formation and accumulation of methylglyoxal derived advanced glycation endproducts (AGEs), prevented structural neuronal damage and normalised head motility and lifespan...
October 1, 2016: Journal of Diabetes and its Complications
Hema Negi, Aparna Shukla, Feroz Khan, Rakesh Pandey
Remarkably the c-Jun-NH2-terminal kinase (JNK) pathway is all evolutionarily conserved across species. In view of the hypothesis that increased stress resistance subdue aging, we investigated the role of ursolic acid (3β-Hydroxy-urs-12-en-28-oic acid; UA) in the pioneering aging model Caenorhabditis elegans with an increase in mean and maximum lifespan by up to 30%. Our genetic study unravelled the underlying pathway where JNK-1 is acting independently of insulin-IGF-1 signalling (IIS) pathway to modulate longevity...
October 20, 2016: Biochemical and Biophysical Research Communications
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...
October 12, 2016: Current Biology: CB
Shaul Yogev, Roshni Cooper, Richard Fetter, Mark Horowitz, Kang Shen
Axonal microtubule (MT) arrays are the major cytoskeleton substrate for cargo transport. How MT organization, i.e., polymer length, number, and minus-end spacing, is regulated and how it impinges on axonal transport are unclear. We describe a method for analyzing neuronal MT organization using light microscopy. This method circumvents the need for electron microscopy reconstructions and is compatible with live imaging of cargo transport and MT dynamics. Examination of a C. elegans motor neuron revealed how age, MT-associated proteins, and signaling pathways control MT length, minus-end spacing, and coverage...
October 19, 2016: Neuron
Antonia Piazzesi, Dražen Papić, Fabio Bertan, Paolo Salomoni, Pierluigi Nicotera, Daniele Bano
Chromatin structure orchestrates the accessibility to the genetic material. Replication-independent histone variants control transcriptional plasticity in postmitotic cells. The life-long accumulation of these histones has been described, yet the implications on organismal aging remain elusive. Here, we study the importance of the histone variant H3.3 in Caenorhabditis elegans longevity pathways. We show that H3.3-deficient nematodes have negligible lifespan differences compared to wild-type animals. However, H3...
October 18, 2016: Cell Reports
Asad Jan, Brandon Jansonius, Alberto Delaidelli, Syam Prakash Somasekharan, Forum Bhanshali, Milène Vandal, Gian Luca Negri, Don Moerman, Ian MacKenzie, Frédéric Calon, Michael R Hayden, Stefan Taubert, Poul H Sorensen
Soluble oligomers of amyloid-β (Aβ) impair synaptic plasticity, perturb neuronal energy homeostasis, and are implicated in Alzheimer's disease (AD) pathogenesis. Therefore, significant efforts in AD drug discovery research aim to prevent the formation of Aβ oligomers or block their neurotoxicity. The eukaryotic elongation factor-2 kinase (eEF2K) plays a critical role in synaptic plasticity, and couples neurotransmission to local dendritic mRNA translation. Recent evidence indicates that Aβ oligomers activate neuronal eEF2K, suggesting a potential link to Aβ induced synaptic dysfunction...
October 17, 2016: Acta Neuropathologica
Amelia Pollard, Freya Shephard, James Freed, Susan Liddell, Lisa Chakrabarti
Carbonic anhydrase inhibitors are used to treat glaucoma and cancers. Carbonic anhydrases perform a crucial role in the conversion of carbon dioxide and water into bicarbonate and protons. However, there is little information about carbonic anhydrase isoforms during the process of ageing. Mitochondrial dysfunction is implicit in ageing brain and muscle. We have interrogated isolated mitochondrial fractions from young adult and middle aged mouse brain and skeletal muscle. We find an increase of tissue specific carbonic anhydrases in mitochondria from middle-aged brain and skeletal muscle...
October 10, 2016: Aging
Li Dong, Matteo Cornaglia, Thomas Lehnert, Martin A M Gijs
Like other animals, C. elegans nematodes have the ability to socially interact and to communicate through exchange and sensing of small soluble signaling compounds that help them cope with complex environmental conditions. For the time being, worm biocommunication assays are being performed mainly on agar plates; however, microfluidic assays may provide significant advantages compared to traditional methods, such as control of signaling molecule concentrations and gradients or confinement of distinct worm populations in different microcompartments...
October 13, 2016: Lab on a Chip
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
William B Zhang, Drew B Sinha, William E Pittman, Erik Hvatum, Nicholas Stroustrup, Zachary Pincus
Although many genetic factors and lifestyle interventions are known to affect the mean lifespan of animal populations, the physiological variation displayed by individuals across their lifespans remains largely uncharacterized. Here, we use a custom culture apparatus to continuously monitor five aspects of aging physiology across hundreds of isolated Caenorhabditis elegans individuals kept in a constant environment from hatching until death. Aggregating these measurements into an overall estimate of senescence, we find two chief differences between longer- and shorter-lived individuals...
October 5, 2016: Cell Systems
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
Dong-Kyu Kim, Tae Ho Kim, Seung-Jae Lee
Aging is the most important risk factor for human neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. Pathologically, these diseases are characterized by the deposition of specific protein aggregates in neurons and glia, representing the impairment of neuronal proteostasis. However, the mechanism by which aging affects the proteostasis system and promotes protein aggregation remains largely unknown. The short lifespan and ample genetic resources of Caenorhabditis elegans (C. elegans) have made this species a favorite model organism for aging research, and the development of proteinopathy models in this organism has helped us to understand how aging processes affect protein aggregation and neurodegeneration...
October 7, 2016: Experimental & Molecular Medicine
Shu G Chen, Vilius Stribinskis, Madhavi J Rane, Donald R Demuth, Evelyne Gozal, Andrew M Roberts, Rekha Jagadapillai, Ruolan Liu, Kyonghwan Choe, Bhooma Shivakumar, Francheska Son, Shunying Jin, Richard Kerber, Anthony Adame, Eliezer Masliah, Robert P Friedland
Misfolded alpha-synuclein (AS) and other neurodegenerative disorder proteins display prion-like transmission of protein aggregation. Factors responsible for the initiation of AS aggregation are unknown. To evaluate the role of amyloid proteins made by the microbiota we exposed aged rats and transgenic C. elegans to E. coli producing the extracellular bacterial amyloid protein curli. Rats exposed to curli-producing bacteria displayed increased neuronal AS deposition in both gut and brain and enhanced microgliosis and astrogliosis compared to rats exposed to either mutant bacteria unable to synthesize curli, or to vehicle alone...
October 6, 2016: Scientific Reports
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
Laurent Mouchiroud, Vincenzo Sorrentino, Evan G Williams, Matteo Cornaglia, Michael V Frochaux, Tao Lin, Amandine A Nicolet-Dit-Félix, Gopal Krishnamani, Tarik Ouhmad, Martin A M Gijs, Bart Deplancke, Johan Auwerx
Phenotyping strategies in simple model organisms such as D. melanogaster and C. elegans are often broadly limited to growth, aging, and fitness. Recently, a number of physical setups and video tracking software suites have been developed to allow for accurate, quantitative, and high-throughput analysis of movement in flies and worms. However, many of these systems require precise experimental setups and/or fixed recording formats. We report here an update to the Parallel Worm Tracker software, which we termed the Movement Tracker...
October 3, 2016: Current Protocols in Neuroscience
Stephanie M Zimmerman, Stuart K Kim
Aging is accompanied by large-scale changes in the proteome, which could have important consequences for cellular and organismal physiology. In this commentary, we review recent studies characterizing the aging proteome in C. elegans. We assess the evidence that the rates of protein synthesis, folding, and degradation change with age in C. elegans, and evaluate whether changes in these pathways limit normal lifespan. We also discuss large-scale studies measuring changes in the proteome with age that suggest that a failure to excrete reproductive proteins in post-reproductive animals plays a role in changing protein levels with age...
2016: Worm
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
Heran Ma, Yudan Ma, Zhixian Zhang, Ziyuan Zhao, Ran Lin, Jinming Zhu, Yi Guo, Li Xu
The antioxidant properties of l-arginine (l-Arg) in vivo, and its effect on enhancing resistance to oxidative stress and heat stress in Caenorhabditis elegans were investigated. C. elegans, a worm model popularly used in molecular and developmental biology, was used in the present study. Here, we report that l-Arg, at a concentration of 1 mM, prolonged C. elegans life by 26.98% and 37.02% under oxidative and heat stress, respectively. Further experiments indicated that the longevity-extending effects of l-Arg may be exerted by its free radical scavenging capacity and the upregulation of aging-associated gene expression in worms...
2016: International Journal of Environmental Research and Public Health
Siegfried Hekimi, Ying Wang, Alycia Noë
It has become clear that mitochondrial reactive oxygen species (mtROS) are not simply villains and mitochondria the hapless targets of their attacks. Rather, it appears that mitochondrial dysfunction itself and the signaling function of mtROS can have positive effects on lifespan, helping to extend longevity. If events in the mitochondria can lead to better cellular homeostasis and better survival of the organism in ways beyond providing ATP and biosynthetic products, we can conjecture that they act on other cellular components through appropriate signaling pathways...
2016: Frontiers in Genetics
David Desjardins, Briseida Cacho-Valadez, Ju-Ling Liu, Ying Wang, Callista Yee, Kristine Bernard, Arman Khaki, Lionel Breton, Siegfried Hekimi
Reactive oxygen species (ROS) are potentially toxic, but they are also signaling molecules that modulate aging. Recent observations that ROS can promote longevity have to be reconciled with the numerous claims about the benefits of antioxidants on lifespan. Here, three antioxidants [N-acetylcysteine (NAC), vitamin C, and resveratrol (RSV)] were tested on Caenorhabditis elegans mutants that alter drug uptake, mitochondrial function, and ROS metabolism. We observed that like pro-oxidants, antioxidants can both lengthen and shorten lifespan, dependent on concentration, genotypes, and conditions...
September 28, 2016: Aging Cell
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