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Elegans aging

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https://www.readbyqxmd.com/read/27919065/splicing-factor-1-modulates-dietary-restriction-and-torc1-pathway-longevity-in-c-elegans
#1
Caroline Heintz, Thomas K Doktor, Anne Lanjuin, Caroline C Escoubas, Yue Zhang, Heather J Weir, Sneha Dutta, Carlos Giovanni Silva-García, Gitte H Bruun, Ianessa Morantte, Gerta Hoxhaj, Brendan D Manning, Brage S Andresen, William B Mair
Ageing is driven by a loss of transcriptional and protein homeostasis and is the key risk factor for multiple chronic diseases. Interventions that attenuate or reverse systemic dysfunction associated with age therefore have the potential to reduce overall disease risk in the elderly. Precursor mRNA (pre-mRNA) splicing is a fundamental link between gene expression and the proteome, and deregulation of the splicing machinery is linked to several age-related chronic illnesses. However, the role of splicing homeostasis in healthy ageing remains unclear...
December 5, 2016: Nature
https://www.readbyqxmd.com/read/27906968/structural-and-functional-recovery-of-sensory-cilia-in-c-elegans-ift-mutants-upon-aging
#2
Astrid Cornils, Ashish K Maurya, Lauren Tereshko, Julie Kennedy, Andrea G Brear, Veena Prahlad, Oliver E Blacque, Piali Sengupta
The majority of cilia are formed and maintained by the highly conserved process of intraflagellar transport (IFT). Mutations in IFT genes lead to ciliary structural defects and systemic disorders termed ciliopathies. Here we show that the severely truncated sensory cilia of hypomorphic IFT mutants in C. elegans transiently elongate during a discrete period of adult aging leading to markedly improved sensory behaviors. Age-dependent restoration of cilia morphology occurs in structurally diverse cilia types and requires IFT...
December 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27905558/microrna-mir-34-provides-robustness-to-environmental-stress-response-via-the-daf-16-network-in-c-elegans
#3
Meltem Isik, T Keith Blackwell, Eugene Berezikov
Diverse stresses and aging alter expression levels of microRNAs, suggesting a role for these posttranscriptional regulators of gene expression in stress modulation and longevity. Earlier studies demonstrated a central role for the miR-34 family in promoting cell cycle arrest and cell death following stress in human cells. However, the biological significance of this response was unclear. Here we show that in C. elegans mir-34 upregulation is necessary for developmental arrest, correct morphogenesis, and adaptation to a lower metabolic state to protect animals against stress-related damage...
December 1, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27903783/uncovering-the-mechanisms-of-caenorhabditis-elegans-ageing-from-global-quantification-of-the-underlying-landscape
#4
Lei Zhao, Jin Wang
Recent studies on Caenorhabditis elegans reveal that gene manipulations can extend its lifespan several fold. However, how the genes work together to determine longevity is still an open question. Here we construct a gene regulatory network for worm ageing and quantify its underlying potential and flux landscape. We found ageing and rejuvenation states can emerge as basins of attraction at certain gene expression levels. The system state can switch from one attractor to another driven by the intrinsic or external perturbations through genetics or the environment...
November 2016: Journal of the Royal Society, Interface
https://www.readbyqxmd.com/read/27892468/somatic-increase-of-cct8-mimics-proteostasis-of-human-pluripotent-stem-cells-and-extends-c-elegans-lifespan
#5
Alireza Noormohammadi, Amirabbas Khodakarami, Ricardo Gutierrez-Garcia, Hyun Ju Lee, Seda Koyuncu, Tim König, Christina Schindler, Isabel Saez, Azra Fatima, Christoph Dieterich, David Vilchez
Human embryonic stem cells can replicate indefinitely while maintaining their undifferentiated state and, therefore, are immortal in culture. This capacity may demand avoidance of any imbalance in protein homeostasis (proteostasis) that would otherwise compromise stem cell identity. Here we show that human pluripotent stem cells exhibit enhanced assembly of the TRiC/CCT complex, a chaperonin that facilitates the folding of 10% of the proteome. We find that ectopic expression of a single subunit (CCT8) is sufficient to increase TRiC/CCT assembly...
November 28, 2016: Nature Communications
https://www.readbyqxmd.com/read/27884963/ectopic-fat-deposition-contributes-to-age-associated-pathology-in-caenorhabditis-elegans
#6
Konstantinos Palikaras, Meropi Mari, Barbara Petanidou, Angela Pasparaki, George Filippidis, Nektarios Tavernarakis
Age-dependent collapse of lipid homeostasis results in spillover of lipids and excessive fat deposition in non-adipose tissues. Ectopic fat contributes to lipotoxicity and has been implicated in the development of a metabolic syndrome that increases risk of age-associated diseases. However, the molecular mechanisms coupling ectopic fat accumulation with ageing remain obscure. Here, we use nonlinear imaging modalities to visualize and quantify age-dependent ectopic lipid accumulation in Caenorhabditis elegans...
November 24, 2016: Journal of Lipid Research
https://www.readbyqxmd.com/read/27882602/the-resveratrol-derivatives-trans-3-5-dimethoxy-4-fluoro-4-hydroxystilbene-and-trans-2-4-5-trihydroxystilbene-decrease-oxidative-stress-and-prolong-lifespan-in-caenorhabditis-elegans
#7
Nadine Fischer, Christian Büchter, Karoline Koch, Sabrina Albert, René Csuk, Wim Wätjen
OBJECTIVES: Resveratrol (trans-3,4',5-trihydroxystilbene (1)) was previously shown to extend the lifespan of different model organisms. However, its pharmacological efficiency is controversially discussed. Therefore, the bioactivity of four newly synthesized stilbenes (trans-3,5-dimethoxy-4-fluoro-4'-hydroxystilbene (3), trans-4'-hydroxy-3,4,5-trifluorostilbene (4), trans-2,5-dimethoxy-4'-hydroxystilbene (5), trans-2,4',5-trihydroxystilbene (6)) was compared to (1) and pterostilbene (trans-3,5-dimethoxy-4'-hydroxystilbene (2)) in the established model organism Caenorhabditis elegans...
November 23, 2016: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/27864060/fos-1-functions-as-a-transcriptional-activator-downstream-of-the-c-elegans-jnk-homolog-kgb-1
#8
Zhe Zhang, Limeng Liu, Kwame Twumasi-Boateng, Dena H S Block, Michael Shapira
JNK proteins are conserved stress-activated MAP kinases. In C. elegans, the JNK-homolog KGB-1 plays essential roles in protection from heavy metals and protein folding stress. However, the contributions of KGB-1 are age-dependent, providing protection in larvae, but reducing stress resistance and shortening lifespan in adults. Attenuation of DAF-16 was linked to the detrimental contributions of KGB-1 in adults, but its involvement in KGB-1-dependent protection in larvae remains unclear. To characterize age-dependent contributions of KGB-1, we used microarray analysis to measure gene expression following KGB-1 activation either in developing larvae or in adults, achieved by knocking down its negative phosphatase regulator vhp-1...
November 15, 2016: Cellular Signalling
https://www.readbyqxmd.com/read/27854075/benzimidazole-derivative-m084-extends-the-lifespan-of-caenorhabditis-elegans-in-a-daf-16-foxo-dependent-way
#9
Ai-Jun Ding, Gui-Sheng Wu, Bin Tang, Xuechuan Hong, Michael X Zhu, Huai-Rong Luo
With the growth of aging population, there is increasing demand to develop strategy to improve the aging process and aging-related diseases. Benzimidazole and its derivatives are crucial heterocyclic backbone of many drugs and compounds with diverse therapeutic applications, including alleviation of aging-related diseases. Here, we investigate if the benzimidazole derivative n-butyl-[1H]-benzimidazol-2-amine (M084), a novel inhibitor of TRPC4 and TRPC5 channels and antidepressant, could affect the lifespan of Caenorhabditis elegans (C...
November 16, 2016: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/27853905/an-antidiabetic-polyherbal-phytomedicine-confers-stress-resistance-and-extends-lifespan-in-caenorhabditis-elegans
#10
Laxmi Rathor, Aakanksha Pant, Harshika Awasthi, Dayanandan Mani, Rakesh Pandey
An Ayurvedic polyherbal extract (PHE) comprising six herbs viz. Berberis aristata, Cyperus rotundus, Cedrus deodara, Emblica officinalis, Terminalia chebula and Terminalia bellirica is mentioned as an effective anti-hyperglycemic agent in 'Charaka Samhita', the classical text of Ayurveda. Previously, antidiabetic drug metformin was found to elicit antiaging effects and PHE was also found to exhibit antidiabetic effects in humans. Therefore, we screened it for its in vivo antioxidant antiaging effect on stress and lifespan using human homologous Caenorhabditis elegans model system...
November 16, 2016: Biogerontology
https://www.readbyqxmd.com/read/27824314/a-serum-mirna-profile-of-human-longevity-findings-from-the-baltimore-longitudinal-study-of-aging-blsa
#11
Thalyana Smith-Vikos, Zuyun Liu, Christine Parsons, Myriam Gorospe, Luigi Ferrucci, Thomas M Gill, Frank J Slack
In C. elegans, miRNAs are genetic biomarkers of aging. Similarly, multiple miRNAs are differentially expressed between younger and older persons, suggesting that miRNA-regulated biological mechanisms affecting aging are evolutionarily conserved. Previous human studies have not considered participants' lifespans, a key factor in identifying biomarkers of aging. Using PCR arrays, we measured miRNA levels from serum samples obtained longitudinally at ages 50, 55, and 60 from 16 non-Hispanic males who had documented lifespans from 58 to 92...
November 7, 2016: Aging
https://www.readbyqxmd.com/read/27810360/delaying-aging-in-caenorhabditis-elegans-with-protein-aggregation-inhibitors
#12
Karina Cuanalo-Contreras, Kyung-Won Park, Abhisek Mukherjee, Lourdes Millán-Pérez Peña, Claudio Soto
Recent evidence suggests that during aging there is widespread accumulation of aggregated insoluble proteins, even in the absence of pathological conditions. Pharmacological manipulation of protein aggregation might be helpful to unveil the involvement of protein aggregates during aging, as well as to develop novel strategies to delay aging. Here we investigated the effect of known protein aggregation inhibitors on the lifespan and health-span of Caenorhabditis elegans. For this purpose, we selected various structurally diverse anti-aggregation compounds and screened them in liquid and solid medium for their ability to alter the rate of aging in vivo...
October 31, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27809888/the-struggle-by-caenorhabditis-elegans-to-maintain-proteostasis-during-aging-and-disease
#13
REVIEW
Elise A Kikis
: The presence of only small amounts of misfolded protein is an indication of a healthy proteome. Maintaining proteome health, or more specifically, "proteostasis," is the purview of the "proteostasis network." This network must respond to constant fluctuations in the amount of destabilized proteins caused by errors in protein synthesis and exposure to acute proteotoxic conditions. Aging is associated with a gradual increase in damaged and misfolded protein, which places additional stress on the machinery of the proteostasis network...
November 3, 2016: Biology Direct
https://www.readbyqxmd.com/read/27803194/quantification-of-in-vivo-progenitor-mutation-accrual-with-ultra-low-error-rate-and-minimal-input-dna-using-sip-hava-seq
#14
Pete H Taylor, Amanda Cinquin, Olivier Cinquin
Assaying in vivo accrual of DNA damage and DNA mutations by stem cells and pinpointing sources of damage and mutations would further our understanding of aging and carcinogenesis. Two main hurdles must be overcome. First, in vivo mutation rates are orders of magnitude lower than raw sequencing error rates. Second, stem cells are vastly outnumbered by differentiated cells, which have a higher mutation rate-quantification of stem cell DNA damage and DNA mutations is thus best performed from small, well-defined cell populations...
November 2016: Genome Research
https://www.readbyqxmd.com/read/27794564/human-exceptional-longevity-transcriptome-from-centenarians-is-distinct-from-septuagenarians-and-reveals-a-role-of-bcl-xl-in-successful-aging
#15
Consuelo Borras, Kheira M Abdelaziz, Juan Gambini, Eva Serna, Marta Inglés, Monica de la Fuente, Idoia Garcia, Ander Matheu, Paula Sanchís, Angel Belenguer, Alessandra Errigo, Juan-Antonio Avellana, Ana Barettino, Carla Lloret-Fernández, Nuria Flames, Gianni Pes, Leocadio Rodriguez-Mañas, Jose Viña
Centenarians not only enjoy an extraordinary aging, but also show a compression of morbidity. Using functional transcriptomic analysis of peripheral blood mononuclear cells (PMBC) we identified 1721 mRNAs differentially expressed by centenarians when compared with septuagenarians and young people. Sub-network analysis led us to identify Bcl - xL as an important gene up-regulated in centenarians. It is involved in the control of apoptosis, cellular damage protection and also in modulation of immune response, all associated to healthy aging...
October 28, 2016: Aging
https://www.readbyqxmd.com/read/27791127/cockayne-syndrome-group-a-and-b-proteins-converge-on-transcription-linked-resolution-of-non-b-dna
#16
Morten Scheibye-Knudsen, Anne Tseng, Martin Borch Jensen, Karsten Scheibye-Alsing, Evandro Fei Fang, Teruaki Iyama, Sanjay Kumar Bharti, Krisztina Marosi, Lynn Froetscher, Henok Kassahun, David Mark Eckley, Robert W Maul, Paul Bastian, Supriyo De, Soumita Ghosh, Hilde Nilsen, Ilya G Goldberg, Mark P Mattson, David M Wilson, Robert M Brosh, Myriam Gorospe, Vilhelm A Bohr
Cockayne syndrome is a neurodegenerative accelerated aging disorder caused by mutations in the CSA or CSB genes. Although the pathogenesis of Cockayne syndrome has remained elusive, recent work implicates mitochondrial dysfunction in the disease progression. Here, we present evidence that loss of CSA or CSB in a neuroblastoma cell line converges on mitochondrial dysfunction caused by defects in ribosomal DNA transcription and activation of the DNA damage sensor poly-ADP ribose polymerase 1 (PARP1). Indeed, inhibition of ribosomal DNA transcription leads to mitochondrial dysfunction in a number of cell lines...
November 1, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27790859/dimethyl-sulfide-protects-against-oxidative-stress-and-extends-lifespan-via-a-methionine-sulfoxide-reductase-a-dependent-catalytic-mechanism
#17
Xin-Lei Guan, Peng-Fei Wu, Sheng Wang, Juan-Juan Zhang, Zu-Cheng Shen, Han Luo, Hao Chen, Li-Hong Long, Jian-Guo Chen, Fang Wang
Methionine (Met) sulfoxide reductase A (MsrA) is a key endogenous antioxidative enzyme with longevity benefits in animals. Only very few approaches have been reported to enhance MsrA function. Recent reports have indicated that the antioxidant capability of MsrA may involve a Met oxidase activity that facilities the reaction of Met with reactive oxygen species (ROS). Herein, we used a homology modeling approach to search the substrates for the oxidase activity of MsrA. We found that dimethyl sulfide (DMS), a main metabolite that produced by marine algae, emerged as a good substrate for MsrA-catalytic antioxidation...
October 28, 2016: Aging Cell
https://www.readbyqxmd.com/read/27788357/uncovering-the-dark-energy-of-aging
#18
Simon Melov
A medically relevant understanding of aging requires an appreciation for how time degrades specific, healthy features of individual organisms over the course of their lives. Zach Pincus and colleagues make a key step in this direction, using C. elegans as a model system.
October 26, 2016: Cell Systems
https://www.readbyqxmd.com/read/27783938/vitamin-d-promotes-protein-homeostasis-and-longevity-via-the-stress-response-pathway-genes-skn-1-ire-1-and-xbp-1
#19
Karla A Mark, Kathleen J Dumas, Dipa Bhaumik, Birgit Schilling, Sonnet Davis, Tal Ronnen Oron, Dylan J Sorensen, Mark Lucanic, Rachel B Brem, Simon Melov, Arvind Ramanathan, Bradford W Gibson, Gordon J Lithgow
Vitamin D has multiple roles, including the regulation of bone and calcium homeostasis. Deficiency of 25-hydroxyvitamin D, the major circulating form of vitamin D, is associated with an increased risk of age-related chronic diseases, including Alzheimer's disease, Parkinson's disease, cognitive impairment, and cancer. In this study, we utilized Caenorhabditis elegans to examine the mechanism by which vitamin D influences aging. We found that vitamin-D3-induced lifespan extension requires the stress response pathway genes skn-1, ire-1, and xbp-1...
October 25, 2016: Cell Reports
https://www.readbyqxmd.com/read/27783623/maternal-diet-and-insulin-like-signaling-control-intergenerational-plasticity-of-progeny-size-and-starvation-resistance
#20
Jonathan D Hibshman, Anthony Hung, L Ryan Baugh
Maternal effects of environmental conditions produce intergenerational phenotypic plasticity. Adaptive value of these effects depends on appropriate anticipation of environmental conditions in the next generation, and mismatch between conditions may contribute to disease. However, regulation of intergenerational plasticity is poorly understood. Dietary restriction (DR) delays aging but maternal effects have not been investigated. We demonstrate maternal effects of DR in the roundworm C. elegans. Worms cultured in DR produce fewer but larger progeny...
October 2016: PLoS Genetics
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