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C elegans aging

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https://www.readbyqxmd.com/read/28698593/differential-adiponectin-signalling-couples-er-stress-with-lipid-metabolism-to-modulate-ageing-in-c-elegans
#1
Emmanouil Kyriakakis, Nikolaos Charmpilas, Nektarios Tavernarakis
The metabolic and endocrine functions of adipose tissue and the ability of organisms to cope with cellular stress have a direct impact on physiological ageing and the aetiology of various diseases such as obesity-related pathologies and cancer. The endocrine effects of adipose tissue are mediated by secreted adipokines, which modulate metabolic processes and influence related maladies. Although a plethora of molecules and signaling pathways associate ageing with proteotoxic stress and cellular metabolism, our understanding of how these pathways interconnect to coordinate organismal physiology remains limited...
July 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28696216/regulation-of-lysosomal-function-by-the-daf-16-forkhead-transcription-factor-couples-reproduction-to-aging-in-caenorhabditis-elegans
#2
Kunal Baxi, Ata Ghavidel, Brandon Waddell, Troy A Harkness, Carlos E de Carvalho
Aging in eukaryotes is accompanied by widespread deterioration of the somatic tissue. Yet, abolishing germ cells delays the age-dependent somatic decline in Caenorhabditis elegans In adult worms lacking germ cells, the activation of the DAF-9/DAF-12 steroid signalling pathway in the gonad recruits DAF-16 activity in the intestine to promote longevity-associated phenotypes. However, the impact of this pathway on the fitness of normally reproducing animals is less clear. Here, we explore the link between progeny production and somatic aging and identify the loss of lysosomal acidity, a critical regulator of the proteolytic output of these organelles, as a novel biomarker of aging in C...
July 10, 2017: Genetics
https://www.readbyqxmd.com/read/28679685/changes-of-protein-turnover-in-aging-caenorhabditis-elegans
#3
Ineke Dhondt, Vladislav A Petyuk, Sophie Bauer, Heather M Brewer, Richard D Smith, Geert Depuydt, Bart P Braeckman
Protein turnover rates severely decline in aging organisms, including C. elegans However, limited information is available on turnover dynamics at the individual protein level during aging. We followed changes in protein turnover at one-day resolution using a multiple-pulse (15)N-labeling and accurate mass spectrometry approach. Forty percent of the proteome shows gradual slowdown in turnover with age, while only few proteins show increased turnover. Decrease in protein turnover was consistent for only a minority of functionally related protein subsets, including tubulins and vitellogenins, while randomly diverging turnover patterns with age were the norm...
July 5, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28679124/pharynx-mitochondrial-ca2-dynamics-in-live-c-elegans-worms-during-aging
#4
Pilar Alvarez-Illera, Paloma García-Casas, Jessica Arias-Del-Val, Rosalba I Fonteriz, Javier Alvarez, Mayte Montero
Progressive decline in mitochondrial function is generally considered one of the hallmarks of aging. We have expressed a Ca2+ sensor in the mitochondrial matrix of C. elegans pharynx cells and we have measured for the first time mitochondrial [Ca2+] ([Ca2+]M) dynamics in the pharynx of live C. elegans worms during aging. Our results show that worms stimulated with serotonin display a pharynx [Ca2+]M oscillatory kinetics that includes both high frequency oscillations (up to about 1Hz) and very prolonged "square-wave" [Ca2+]M increases, indicative of energy depletion of the pharynx cells...
June 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28675140/spatiotemporal-regulation-of-autophagy-during-caenorhabditis-elegans-aging
#5
Jessica T Chang, Caroline Kumsta, Andrew B Hellman, Linnea M Adams, Malene Hansen
Autophagy has been linked to longevity in many species, but the underlying mechanisms are unclear. Using a GFP-tagged and a new tandem-tagged Atg8/LGG-1 reporter, we quantified autophagic vesicles and performed autophagic flux assays in multiple tissues of wild-type Caenorhabditis elegans and long-lived daf-2/insulin/IGF-1 and glp-1/Notch mutants throughout adulthood. Our data are consistent with an age-related decline in autophagic activity in the intestine, body-wall muscle, pharynx, and neurons of wild-type animals...
July 4, 2017: ELife
https://www.readbyqxmd.com/read/28674941/coffee-extract-and-caffeine-enhance-the-heat-shock-response-and-promote-proteostasis-in-an-hsf-1-dependent-manner-in-caenorhabditis-elegans
#6
Jessica Brunquell, Stephanie Morris, Alana Snyder, Sandy D Westerheide
As the population ages, there is a critical need to uncover strategies to combat diseases of aging. Studies in the soil-dwelling nematode Caenorhabditis elegans have demonstrated the protective effects of coffee extract and caffeine in promoting the induction of conserved longevity pathways including the insulin-like signaling pathway and the oxidative stress response. We were interested in determining the effects of coffee and caffeine treatment on the regulation of the heat shock response. The heat shock response is a highly conserved cellular response that functions as a cytoprotective mechanism during stress, mediated by the heat shock transcription factor HSF-1...
July 4, 2017: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/28673026/3%C3%AE-hydroxy-urs-12-en-28-oic-acid-modulates-dietary-restriction-mediated-longevity-and-ameliorates-toxic-protein-aggregation-in-c-elegans
#7
Hema Negi, Shilpi Khare Saikia, Rakesh Pandey
Species from lower invertebrates to a spectrum of mammals show anti-aging health benefits of phytochemical(s). Here, we explored the pro-longevity effects of a natural triterpenoid, ursolic acid (3β-hydroxy-urs-12-en-28-oic acid; UA) in Caenorhabditis elegans with maximal lifespan being evident at 25µM UA. Similar to eat-2 mutants, UA uptake by worm results in reduced fat storage and attenuation of reactive oxygen species (ROS), independent of superoxide dismutase(s) activation. The genetic requirements for UA mediated longevity are quite similar to dietary restriction (DR) achieved through SKN-1/ NRF-2 exhibiting up regulation of downstream target genes gcs-1 and daf-9...
June 30, 2017: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/28669960/-effect-of-herba-scutellariae-barbatae-flavonoids-in-delaying-aging-of-caenorhabditis-elegans-and-human-umbilical-vein-endothelial-cells-in-vitro
#8
Wei Zhou, Jing-Ming Lin, Su-Li Wang, Hai-Zhen Lin
OBJECTIVE: To explore the effects of Herba Scutellariae Barbatae flavonoids (HF) in delaying aging of Caenorhabditis elegans and human umbilical vein endothelial cells (HUVECs) in vitro. METHODS: The effects of 30 or 50 mg/L of HF on nematode life span, reproductive capacity, oxidative stress, and antioxidant enzyme activity of C. elegans were assessed, and the effects of HF on the expressions of the genes encoding antioxidant enzymes and the aging-related genes were analyzed using real-time RT-PCR in both C...
June 20, 2017: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
https://www.readbyqxmd.com/read/28667441/lifespan-extending-and-stress-resistance-properties-of-brazilin-from-caesalpinia-sappan-in-caenorhabditis-elegans
#9
Eun Byeol Lee, Ming Ming Xing, Dae Keun Kim
This study contributes to the continual discovery of lifespan-extending compounds from plants, using the Caenorhabditis elegans model system. An ethyl acetate soluble fraction of methanol extract from the heartwood of Caesalpinia sappan showed a significant lifespan-extending activity. Subsequent activity-guided chromatography of the ethyl acetate-soluble fraction led to the isolation of brazilin. Brazilin showed potent 2,2-diphenyl-1-picrylhydrazyl radical scavenging and superoxide anion quenching activities and also revealed a lifespan-extending activity in C...
June 30, 2017: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/28659967/behavioral-phenotyping-and-pathological-indicators-of-parkinson-s-disease-in-c-elegans-models
#10
REVIEW
Malabika Maulik, Swarup Mitra, Abel Bult-Ito, Barbara E Taylor, Elena M Vayndorf
Parkinson's disease (PD) is a neurodegenerative disorder with symptoms that progressively worsen with age. Pathologically, PD is characterized by the aggregation of α-synuclein in cells of the substantia nigra in the brain and loss of dopaminergic neurons. This pathology is associated with impaired movement and reduced cognitive function. The etiology of PD can be attributed to a combination of environmental and genetic factors. A popular animal model, the nematode roundworm Caenorhabditis elegans, has been frequently used to study the role of genetic and environmental factors in the molecular pathology and behavioral phenotypes associated with PD...
2017: Frontiers in Genetics
https://www.readbyqxmd.com/read/28644434/ageing-and-hypoxia-cause-protein-aggregation-in-mitochondria
#11
Daniel M Kaufman, Xia Wu, Barbara A Scott, Omar A Itani, Marc R Van Gilst, James E Bruce, C Michael Crowder
Aggregation of cytosolic proteins is a pathological finding in disease states, including ageing and neurodegenerative diseases. We have previously reported that hypoxia induces protein misfolding in Caenorhabditis elegans mitochondria, and electron micrographs suggested protein aggregates. Here, we seek to determine whether mitochondrial proteins actually aggregate after hypoxia and other cellular stresses. To enrich for mitochondrial proteins that might aggregate, we performed a proteomics analysis on purified C...
June 23, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28638078/the-stress-response-factor-daf-16-foxo-is-required-for-multiple-compound-families-to-prolong-the-function-of-neurons-with-huntington-s-disease
#12
Francesca Farina, Emmanuel Lambert, Lucie Commeau, François-Xavier Lejeune, Nathalie Roudier, Cosima Fonte, J Alex Parker, Jacques Boddaert, Marc Verny, Etienne-Emile Baulieu, Christian Neri
Helping neurons to compensate for proteotoxic stress and maintain function over time (neuronal compensation) has therapeutic potential in aging and neurodegenerative disease. The stress response factor FOXO3 is neuroprotective in models of Huntington's disease (HD), Parkinson's disease and motor-neuron diseases. Neuroprotective compounds acting in a FOXO-dependent manner could thus constitute bona fide drugs for promoting neuronal compensation. However, whether FOXO-dependent neuroprotection is a common feature of several compound families remains unknown...
June 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28632756/identification-of-atf-7-and-the-insulin-signaling-pathway-in-the-regulation-of-metallothionein-in-c-elegans-suggests-roles-in-aging-and-reactive-oxygen-species
#13
Julie A Hall, Matthew K McElwee, Jonathan H Freedman
It has been proposed that aging results from the lifelong accumulation of intracellular damage via reactions with reactive oxygen species (ROS). Metallothioneins are conserved cysteine-rich proteins that function as efficient ROS scavengers and may affect longevity. To better understand mechanisms controlling metallothionein expression, the regulatory factors and pathways that controlled cadmium-inducible transcription of the C. elegans metallothionein gene, mtl-1, were identified. The transcription factor ATF-7 was identified in both ethylmethanesulfonate mutagenesis and candidate gene screens...
2017: PloS One
https://www.readbyqxmd.com/read/28627510/glycogen-controls-caenorhabditis-elegans-lifespan-and-resistance-to-oxidative-stress
#14
Ivan Gusarov, Bibhusita Pani, Laurent Gautier, Olga Smolentseva, Svetlana Eremina, Ilya Shamovsky, Olga Katkova-Zhukotskaya, Alexander Mironov, Evgeny Nudler
A high-sugar diet has been associated with reduced lifespan in organisms ranging from worms to mammals. However, the mechanisms underlying the harmful effects of glucose are poorly understood. Here we establish a causative relationship between endogenous glucose storage in the form of glycogen, resistance to oxidative stress and organismal aging in Caenorhabditis elegans. We find that glycogen accumulated on high dietary glucose limits C. elegans longevity. Glucose released from glycogen and used for NADPH/glutathione reduction renders nematodes and human hepatocytes more resistant against oxidative stress...
June 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28622510/microbial-genetic-composition-tunes-host-longevity
#15
Bing Han, Priya Sivaramakrishnan, Chih-Chun J Lin, Isaiah A A Neve, Jingquan He, Li Wei Rachel Tay, Jessica N Sowa, Antons Sizovs, Guangwei Du, Jin Wang, Christophe Herman, Meng C Wang
Homeostasis of the gut microbiota critically influences host health and aging. Developing genetically engineered probiotics holds great promise as a new therapeutic paradigm to promote healthy aging. Here, through screening 3,983 Escherichia coli mutants, we discovered that 29 bacterial genes, when deleted, increase longevity in the host Caenorhabditis elegans. A dozen of these bacterial mutants also protect the host from age-related progression of tumor growth and amyloid-beta accumulation. Mechanistically, we discovered that five bacterial mutants promote longevity through increased secretion of the polysaccharide colanic acid (CA), which regulates mitochondrial dynamics and unfolded protein response (UPR(mt)) in the host...
June 15, 2017: Cell
https://www.readbyqxmd.com/read/28622501/microbiome-and-longevity-gut-microbes-send-signals-to-host-mitochondria
#16
Jan Gruber, Brian K Kennedy
The microbiome has emerged as a major determinant of the functioning of host organisms, affecting both health and disease. Here, Han et al. use the workhorse of aging research, C. elegans, to identify specific mechanisms by which gut bacteria influence mitochondrial dynamics and aging, a first step toward analogous manipulations to modulate human aging.
June 15, 2017: Cell
https://www.readbyqxmd.com/read/28620943/drug-repurposing-for-aging-research-using-model-organisms
#17
Matthias Ziehm, Satwant Kaur, Dobril K Ivanov, Pedro J Ballester, David Marcus, Linda Partridge, Janet M Thornton
Many increasingly prevalent diseases share a common risk factor: age. However, little is known about pharmaceutical interventions against aging, despite many genes and pathways shown to be important in the aging process and numerous studies demonstrating that genetic interventions can lead to a healthier aging phenotype. An important challenge is to assess the potential to repurpose existing drugs for initial testing on model organisms, where such experiments are possible. To this end, we present a new approach to rank drug-like compounds with known mammalian targets according to their likelihood to modulate aging in the invertebrates Caenorhabditis elegans and Drosophila...
June 16, 2017: Aging Cell
https://www.readbyqxmd.com/read/28612944/the-skn-1-nrf2-transcription-factor-can-protect-against-oxidative-stress-and-increase-lifespan-in-c-%C3%A2-elegans-by-distinct-mechanisms
#18
Jennifer M A Tullet, James W Green, Catherine Au, Alexandre Benedetto, Maximillian A Thompson, Emily Clark, Ann F Gilliat, Adelaide Young, Kathrin Schmeisser, David Gems
In C. elegans, the skn-1 gene encodes a transcription factor that resembles mammalian Nrf2 and activates a detoxification response. skn-1 promotes resistance to oxidative stress (Oxr) and also increases lifespan, and it has been suggested that the former causes the latter, consistent with the theory that oxidative damage causes aging. Here, we report that effects of SKN-1 on Oxr and longevity can be dissociated. We also establish that skn-1 expression can be activated by the DAF-16/FoxO transcription factor, another central regulator of growth, metabolism, and aging...
June 14, 2017: Aging Cell
https://www.readbyqxmd.com/read/28602540/deficiencies-in-mitochondrial-dynamics-sensitize-caenorhabditis-elegans-to-arsenite-and-other-mitochondrial-toxicants-by-reducing-mitochondrial-adaptability
#19
Anthony L Luz, Tewodros R Godebo, Latasha L Smith, Tess C Leuthner, Laura L Maurer, Joel N Meyer
Mitochondrial fission, fusion, and mitophagy are interlinked processes that regulate mitochondrial shape, number, and size, as well as metabolic activity and stress response. The fundamental importance of these processes is evident in the fact that mutations in fission (DRP1), fusion (MFN2, OPA1), and mitophagy (PINK1, PARK2) genes can cause human disease (collectively >1/10,000). Interestingly, however, the age of onset and severity of clinical manifestations varies greatly between patients with these diseases (even those harboring identical mutations), suggesting a role for environmental factors in the development and progression of certain mitochondrial diseases...
June 8, 2017: Toxicology
https://www.readbyqxmd.com/read/28600327/the-oxidative-stress-response-in-caenorhabditis-elegans-requires-the-gata-transcription-factor-elt-3-and-skn-1-nrf2
#20
Queenie Hu, Dayana R D'Amora, Lesley T MacNeil, Albertha J M Walhout, Terrance J Kubiseski
Cellular damage caused by reactive oxygen species (ROS) is believed to be a major contributor to age-associated diseases. Previously, we characterized the C. elegans Brap2 ortholog (BRAP-2) and found that it is required to prevent larval arrest in response to elevated levels of oxidative stress. Here, we report that C. elegans brap-2 mutants display increased expression of SKN-1-dependent phase II detoxification enzymes that is dependent on PMK-1 (a p38 MAP kinase C. elegans ortholog). An RNAi screen was conducted using a transcription factor library to identify genes required for increased expression of the SKN-1 target gst-4 in brap-2 mutants...
June 9, 2017: Genetics
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