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Life extension c elegans

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
Lan Chen, Ju Zhang, Jie Xu, Lu Wan, Kaixuan Teng, Jin Xiang, Rui Zhang, Zebo Huang, Yongmei Liu, Wenhua Li, Xin Liu
The scorpion has been extensively used in various pharmacological profiles or as food supplies. The exploration of scorpion venom has been reported due to the presence of recombinant peptides. rBmαTX14 is an α-neurotoxin extracted from the venom gland of the East Asian scorpion Buthus martensii Karsch and can affect ion channel conductance. Here, we investigated the functions of rBmαTX14 using the Caenorhabditis elegans model. Using western blot analysis, rBmαTX14 was shown to be expressed both in the cytoplasm and inclusion bodies in the E...
2016: PloS One
Erin Munkácsy, Maruf H Khan, Rebecca K Lane, Megan B Borror, Jae H Park, Alex F Bokov, Alfred L Fisher, Christopher D Link, Shane L Rea
Mitochondrial dysfunction underlies numerous age-related pathologies. In an effort to uncover how the detrimental effects of mitochondrial dysfunction might be alleviated, we examined how the nematode C. elegans not only adapts to disruption of the mitochondrial electron transport chain, but in many instances responds with extended lifespan. Studies have shown various retrograde responses are activated in these animals, including the well-studied ATFS-1-dependent mitochondrial unfolded protein response (UPRmt)...
July 2016: PLoS Genetics
Sandeep Kumar, Nicholas Dietrich, Kerry Kornfeld
Animal aging is characterized by progressive, degenerative changes in many organ systems. Because age-related degeneration is a major contributor to disability and death in humans, treatments that delay age-related degeneration are desirable. However, no drugs that delay normal human aging are currently available. To identify drugs that delay age-related degeneration, we used the powerful Caenorhabditis elegans model system to screen for FDA-approved drugs that can extend the adult lifespan of worms. Here we show that captopril extended mean lifespan...
February 2016: PLoS Genetics
Cheng-Wei Wu, Kenneth B Storey
The biological process of aging is the primary determinant of lifespan, but the factors that influence the rate of aging are not yet clearly understood and remain a challenging question. Mammals are characterized by >100-fold differences in maximal lifespan, influenced by relative variances in body mass and metabolic rate. Recent discoveries have identified long-lived mammalian species that deviate from the expected longevity quotient. A commonality among many long-lived species is the capacity to undergo metabolic rate depression, effectively re-programming normal metabolism in response to extreme environmental stress and enter states of torpor or hibernation...
February 2016: Biomolecular Concepts
Shaun Calvert, Robi Tacutu, Samim Sharifi, Rute Teixeira, Pratul Ghosh, João Pedro de Magalhães
Caloric restriction (CR), a reduction in calorie intake without malnutrition, retards aging in several animal models from worms to mammals. Developing CR mimetics, compounds that reproduce the longevity benefits of CR without its side effects, is of widespread interest. Here, we employed the Connectivity Map to identify drugs with overlapping gene expression profiles with CR. Eleven statistically significant compounds were predicted as CR mimetics using this bioinformatics approach. We then tested rapamycin, allantoin, trichostatin A, LY-294002 and geldanamycin in Caenorhabditis elegans...
April 2016: Aging Cell
Nicole E Seah, C Daniel de Magalhaes Filho, Anna P Petrashen, Hope R Henderson, Jade Laguer, Julissa Gonzalez, Andrew Dillin, Malene Hansen, Louis R Lapierre
Autophagy-dependent longevity models in C. elegans display altered lipid storage profiles, but the contribution of lipid distribution to life-span extension is not fully understood. Here we report that lipoprotein production, autophagy and lysosomal lipolysis are linked to modulate life span in a conserved fashion. We find that overexpression of the yolk lipoprotein VIT/vitellogenin reduces the life span of long-lived animals by impairing the induction of autophagy-related and lysosomal genes necessary for longevity...
2016: Autophagy
Jeong-Hoon Hahm, Sunhee Kim, Race DiLoreto, Cheng Shi, Seung-Jae V Lee, Coleen T Murphy, Hong Gil Nam
Ageing is marked by physical decline. Caenorhabditis elegans is a valuable model for identifying genetic regulatory mechanisms of ageing and longevity. Here we report a simple method to assess C. elegans' maximum physical ability based on the worms' maximum movement velocity. We show maximum velocity declines with age, correlates well with longevity, accurately reports movement ability and, if measured in mid-adulthood, is predictive of maximal lifespan. Contrary to recent findings, we observe that maximum velocity of worm with mutations in daf-2(e1370) insulin/IGF-1 signalling scales with lifespan...
November 20, 2015: Nature Communications
Nausicaa Poullet, Anne Vielle, Clotilde Gimond, Céline Ferrari, Christian Braendle
Thermal developmental plasticity represents a key organismal adaptation to maintain reproductive capacity in contrasting and fluctuating temperature niches. Although extensively studied, research on thermal plasticity has mainly focused on phenotypic outcomes, such as adult life history, rather than directly measuring plasticity of underlying developmental processes. How thermal plasticity of developmental phenotypes maps into plasticity of resulting final phenotypes, and how such mapping relationships evolve, thus remain poorly understood...
November 2015: Evolution & Development
Nadine Urban, Dimitrios Tsitsipatis, Andrea Gille, Ingrit Hamann, Xiaoqing Hou, Lars-Oliver Klotz
Diethyl maleate (DEM) is a thiol-depleting agent frequently employed in cell culture analyses. Here, we investigated the effect of DEM exposure on insulin signaling at the level of FoxO transcription factor activity and its potential consequences for stress resistance and life span. Exposure of HepG2 human hepatoma cells to subcytotoxic concentrations of DEM resulted in nuclear accumulation of overexpressed EGFP-tagged FoxO1a. DEM-induced nuclear accumulation overrode insulin-induced nuclear exclusion of FoxO1a...
October 2014: Free Radical Biology & Medicine
Jyotsna Asthana, Deepti Yadav, Aakanksha Pant, A K Yadav, M M Gupta, Rakesh Pandey
The advancements in the field of gerontology have unraveled the signaling pathways that regulate life span, suggesting that it might be feasible to modulate aging. To this end, we isolated a novel phytomolecule Acacetin 7-O-α-l-rhamnopyranosyl (1-2) β-D-xylopyranoside (ARX) from Premna integrifolia and evaluated its antiaging effects in Caenorhabditis elegans The spectral data analysis revealed the occurrence of a new compound ARX. Out of the three tested pharmacological doses of ARX, viz. 5, 25, and 50 µM, the 25-µM dose was able to extend life span in C...
September 2016: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
Franziska Schwarz, Zehra Karadeniz, Antje Fischer-Rosinsky, Diana M Willmes, Joachim Spranger, Andreas L Birkenfeld
Reducing the expression of the Indy (Acronym for 'I'm Not Dead, Yet') gene in lower organisms promotes longevity and leads to a phenotype that resembles various aspects of caloric restriction. In C. elegans, the available data on life span extension is controversial. Therefore, the aim of this study was to determine the role of the C. elegans INDY homolog CeNAC2 in life span regulation and to delineate possible molecular mechanisms. siRNA against Indy/CeNAC2 was used to reduce expression of Indy/CeNAC2. Mean life span was assessed in four independent experiments, as well as whole body fat content and AMPK activation...
August 2015: Aging
Albert Tzong-Yang Chen, Chunfang Guo, Omar A Itani, Breane G Budaitis, Travis W Williams, Christopher E Hopkins, Richard C McEachin, Manjusha Pande, Ana R Grant, Sawako Yoshina, Shohei Mitani, Patrick J Hu
FoxO transcription factors promote longevity across taxa. How they do so is poorly understood. In the nematode Caenorhabditis elegans, the A- and F-isoforms of the FoxO transcription factor DAF-16 extend life span in the context of reduced DAF-2 insulin-like growth factor receptor (IGFR) signaling. To elucidate the mechanistic basis for DAF-16/FoxO-dependent life span extension, we performed an integrative analysis of isoform-specific daf-16/FoxO mutants. In contrast to previous studies suggesting that DAF-16F plays a more prominent role in life span control than DAF-16A, isoform-specific daf-16/FoxO mutant phenotypes and whole transcriptome profiling revealed a predominant role for DAF-16A over DAF-16F in life span control, stress resistance, and target gene regulation...
October 2015: Genetics
A Pant, J Asthana, A K Yadav, L Rathor, S Srivastava, M M Gupta, R Pandey
The discovery of bioactive molecules modulating aging in living organism promotes development of natural therapeutics for curing age-related afflictions. The progression in age-related disorders can be attributed to increment in intracellular reactive oxygen species (ROS) and oxidative stress level. To this end, we isolated an iridoid verminoside (VMS) from Stereospermum suaveolens (Roxb.) DC. and evaluated its effect on Caenorhabditis elegans. The present study delineates VMS-mediated alteration of intracellular ROS, oxidative stress, and life span in C...
2015: Free Radical Research
Alfonso Schiavi, Silvia Maglioni, Konstantinos Palikaras, Anjumara Shaik, Flavie Strappazzon, Vanessa Brinkmann, Alessandro Torgovnick, Natascha Castelein, Sasha De Henau, Bart P Braeckman, Francesco Cecconi, Nektarios Tavernarakis, Natascia Ventura
Frataxin is a nuclear-encoded mitochondrial protein involved in the biogenesis of Fe-S-cluster-containing proteins and consequently in the functionality of the mitochondrial respiratory chain. Similar to other proteins that regulate mitochondrial respiration, severe frataxin deficiency leads to pathology in humans--Friedreich's ataxia, a life-threatening neurodegenerative disorder--and to developmental arrest in the nematode C. elegans. Interestingly, partial frataxin depletion extends C. elegans lifespan, and a similar anti-aging effect is prompted by reduced expression of other mitochondrial regulatory proteins from yeast to mammals...
July 20, 2015: Current Biology: CB
Christian Büchter, Liang Zhao, Susannah Havermann, Sebastian Honnen, Gerhard Fritz, Peter Proksch, Wim Wätjen
2,3,5,4'-Tetrahydroxystilbene-2-O-β-D-glucoside (TSG) was isolated from Polygonum multiflorum, a plant which is traditionally used as an anti-ageing drug. We have analysed ageing-related effects of TSG in the model organism C. elegans in comparison to resveratrol. TSG exerted a high antioxidative capacity both in a cell-free assay and in the nematode. The antioxidative capacity was even higher compared to resveratrol. Presumably due to its antioxidative effects, treatment with TSG decreased the juglone-mediated induction of the antioxidative enzyme SOD-3; the induction of the GST-4 by juglone was diminished slightly...
2015: Oxidative Medicine and Cellular Longevity
Manish Rauthan, Parmida Ranji, Ragda Abukar, Marc Pilon
The mevalonate pathway is responsible for the synthesis of cholesterol, coenzyme Q, and prenyl groups essential for small GTPase modification and function, and for the production of dolichols important for protein glycosylation. Statins, i.e., cholesterol-lowering drugs that inhibit the rate-limiting enzyme in the mevalonate pathway, HMG-CoA reductase, are lethal to Caenorhabditis elegans even though this animal lacks the branch of the mevalonate pathway that leads to cholesterol synthesis. To better understand the effects of statins that are not related to cholesterol, we have adopted the strategy of isolating statin-resistant C...
August 2015: G3: Genes—Genomes—Genetics
Bi Zhang, Rui Xiao, Elizabeth A Ronan, Yongqun He, Ao-Lin Hsu, Jianfeng Liu, X Z Shawn Xu
Temperature profoundly affects aging in both poikilotherms and homeotherms. A general belief is that lower temperatures extend lifespan, whereas higher temperatures shorten it. Although this "temperature law" is widely accepted, it has not been extensively tested. Here, we systematically evaluated the role of temperature in lifespan regulation in C. elegans. We found that, although exposure to low temperatures at the adult stage prolongs lifespan, low-temperature treatment at the larval stage surprisingly reduces lifespan...
June 9, 2015: Cell Reports
Jiao Li, Xiaodong Cui, Zhuanhua Wang, Yuying Li
Buckwheat trypsin inhibitor (BTI) is a low molecular weight polypeptide extracted from buckwheat. This study examined the effects of BTI on the lifespan of Caenorhabditis elegans (C. elegans) and investigated the mechanism involved. Our results showed that recombinant BTI (rBTI) extended life expectancy by mimicking calorie restriction (CR) in C. elegans. rBTI promoted formation of reactive oxygen species (ROS) via increasing respiration, induced activities of ROS defense enzymes by activating DAF-16, and increased oxidative stress resistance and survival rates...
July 2015: Experimental Gerontology
Alison Callahan, Juan José Cifuentes, Michel Dumontier
BACKGROUND: Extensive studies have been carried out on Caenorhabditis elegans as a model organism to elucidate mechanisms of aging and the effects of perturbing known aging-related genes on lifespan and behavior. This research has generated large amounts of experimental data that is increasingly difficult to integrate and analyze with existing databases and domain knowledge. To address this challenge, we demonstrate a scalable and effective approach for automatic evidence gathering and evaluation that leverages existing experimental data and literature-curated facts to identify genes involved in aging and lifespan regulation in C...
2015: BMC Bioinformatics
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