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Lin Zhou, Lu Wang, Shuju Bai, Shu Xing, Wannan Li, Junfeng Ma, Xueqi Fu
Low molecular weight protein tyrosine phosphatase (LMW-PTP) is highly conserved across almost all living organisms and is involved in the modulation of a number of cellular proteins related to important signaling pathways. In this study, we isolated lmwptp (Y94H6A.7) of Caenorhabditis elegans, the homolog of human ACP1, and set up an effective feeding-based RNA interference (RNAi) knockdown against this gene. We found that knockdown of lmwptp decreased damage associated with heat shock, oxidative stress and UV irradiation in wild-type worms, however, its deficiency didn't further reduce the stress resistance of hsf-1 or daf-16 mutants and didn't further increase the stress sensitivity associated with age-1, akt-1 or akt-2 mutants, but it enhanced the stress resistance of daf-2 mutants...
March 7, 2018: International Journal of Biological Macromolecules
Heather L Bennett, Yulia Khoruzhik, Dustin Hayden, Huiyan Huang, Jarred Sanders, Melissa B Walsh, David Biron, Anne C Hart
BACKGROUND: Sleep deprivation impairs learning, causes stress, and can lead to death. Notch and JNK-1 pathways impact C. elegans sleep in complex ways; these have been hypothesized to involve compensatory sleep. C. elegans DAF-16, a FoxO transcription factor, is required for homeostatic response to decreased sleep and DAF-16 loss decreases survival after sleep bout deprivation. Here, we investigate connections between these pathways and the requirement for sleep after mechanical stress...
March 9, 2018: BMC Neuroscience
Megan M Senchuk, Dylan J Dues, Claire E Schaar, Benjamin K Johnson, Zachary B Madaj, Megan J Bowman, Mary E Winn, Jeremy M Van Raamsdonk
Mild deficits in mitochondrial function have been shown to increase lifespan in multiple species including worms, flies and mice. Here, we study three C. elegans mitochondrial mutants (clk-1, isp-1 and nuo-6) to identify overlapping genetic pathways that contribute to their longevity. We find that genes regulated by the FOXO transcription factor DAF-16 are upregulated in all three strains, and that the transcriptional changes present in these worms overlap significantly with the long-lived insulin-IGF1 signaling pathway mutant daf-2...
March 9, 2018: PLoS 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
Liangping Su, Hongyuan Li, Cheng Huang, Tingting Zhao, Yongjun Zhang, Xueqing Ba, Zhongwei Li, Yu Zhang, Baiqu Huang, Jun Lu, Yanmei Zhao, Xiaoxue Li
Mounting evidence shows that histone methylation, a typical epigenetic mark, is crucial for gene expression regulation during aging. Decreased trimethylation of Lys 36 on histone H3 (H3K36me3) in worms and yeast is reported to shorten lifespan. The function of H3K36me2 in aging remains unclear. In this study, we identified Caenorhabditis elegans SET-18 as a histone H3K36 dimethyltransferase. SET-18 deletion extended lifespan and increased oxidative stress resistance, dependent on daf-16 activity in the insulin/IGF pathway...
March 6, 2018: Cell Reports
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
Bernadette Hotzi, Mónika Kosztelnik, Balázs Hargitai, Krisztina Takács-Vellai, János Barna, Kincső Bördén, András Málnási-Csizmadia, Mónika Lippai, Csaba Ortutay, Caroline Bacquet, Angela Pasparaki, Tamás Arányi, Nektarios Tavernarakis, Tibor Vellai
A fascinating aspect of sexual dimorphism in various animal species is that the two sexes differ substantially in lifespan. In humans, for example, women's life expectancy exceeds that of men by 3-7 years. Whether this trait can be attributed to dissimilar lifestyles or genetic (regulatory) factors remains to be elucidated. Herein, we demonstrate that in the nematode Caenorhabditis elegans, the significantly longer lifespan of hermaphrodites-which are essentially females capable of sperm production-over males is established by TRA-1, the terminal effector of the sex-determination pathway...
March 1, 2018: Aging Cell
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
Heidi A Tissenbaum
In Caenorhabditis elegans, there is a single FOXO transcription factor homolog, encoded by the gene, daf-16. As a central regulator for multiple signaling pathways, DAF-16 integrates these signals which results in modulation of several biological processes including longevity, development, fat storage, stress resistance, innate immunity, and reproduction. Using C. elegans allows for studies of FOXO in the context of the whole animal. Therefore, manipulating levels or the activity of daf-16 results in phenotypic changes...
2018: Current Topics in Developmental Biology
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
Lalit Kumar, Shamsuzzama, Pooja Jadiya, Rizwanul Haque, Shikha Shukla, Aamir Nazir
Circular RNAs (circRNAs) are peculiar non-coding RNA molecules which are known to be present across taxa. Considering the body of evidence that establishes critical functions of non-coding RNA molecules, we endeavored to study circRNAs in the context of Parkinson's disease (PD). Employing transgenic C. elegans model of PD, we used RNase R-mediated cleavage of linear RNA followed by divergent primer-based amplifications towards identifying circzip-2, a novel circRNA molecule. We went on to sequence circzip-2 which is synthesized from functionally important gene zip-2...
January 23, 2018: Molecular Neurobiology
Fanhui Meng, Jun Li, Yanqiu Rao, Wenjun Wang, Yan Fu
Alzheimer's disease (AD) is an age-related neurodegenerative disorder, and the few drugs that are currently available only treat the symptoms. Traditional medicine or phytotherapy has been shown to protect against AD. In our previous studies, Gengnianchun (GNC), a traditional Chinese medicine formula with a prolongevity effect, protected against A β -induced cytotoxicity in pheochromocytoma cells (PC-12 cells) and hippocampal cells. Here, we investigated the effects and possible mechanisms by which GNC protected against A β toxicity using transgenic Caenorhabditis elegans CL4176...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
Gayeung Kwon, Jiyun Lee, Jong-Ho Koh, Young-Hee Lim
Butyricicoccus pullicaecorum and Megasphaera elsdenii inhabit the human intestine and have probiotic potential. The aim of this study was to evaluate the effects of B. pullicaecorum and M. elsdenii on the lifespan of Caenorhabditis elegans. They significantly (P < 0.05) extended the lifespan of C. elegans compared with Escherichia coli OP50, a standard food for the worm. Analysis of age-related biomarkers such as lipofuscin, body size, and locomotory activity showed that they retarded aging. They all failed to extend the lifespan of daf-12 or dbl-1 loss-of-function C...
December 8, 2017: Current Microbiology
Wei Chen, Hong-Ru Lin, Cong-Min Wei, Xiao-Hua Luo, Meng-Lu Sun, Zhen-Zhou Yang, Xin-Yan Chen, Hong-Bing Wang
Cistanche deserticola has been found to exert protection against aging and age-related diseases, but mechanisms underlying its longevity effects remain largely unclear. Here, the multicellular model organism Caenorhabditis elegans was employed to identify lifespan extending and protective effects against β-amyloid (Aβ) induced toxicity by echinacoside (ECH), a phenylethanoid glycoside isolated from C. deserticola. Our results showed that ECH extends the mean lifespan of worms and increases their survival under oxidative stress...
February 2018: Biogerontology
Matthias Rieckher, Stylianos E Psycharakis Daniele Ancora, Evangelos Liapis, Athanasios Zacharopoulos, Jorge Ripoll, Nektarios Tavernarakis, Giannis Zacharakis
Optical microscopy constitutes, one of the most fundamental paradigms for the understanding of complex biological mechanisms in the whole-organism and live-tissue context. Novel imaging techniques such as light sheet fluorescence microscopy (LSFM) and optical projection tomography (OPT) combined with phase-retrieval algorithms (PRT) can produce highly resolved 3D images in multiple transport-mean-free-path scales. Our study aims to exemplify the microscopic capabilities of LSFM when imaging protein dynamics in Caenorhabditis elegans and the distribution of necrotic cells in cancer cell spheroids...
January 2018: Biotechnology Journal
Papri Nag, Pooja Rani Aggarwal, Sudip Ghosh, Kanika Narula, Rajul Tayal, Nidhi Maheshwari, Niranjan Chakraborty, Subhra Chakraborty
Although precisely controlled innate immune response is governed by conserved cellular events in phylogenetically diverse hosts, the underlying molecular mechanisms by which this process is regulated against a multi-host pathogen remain unknown. Fusarium oxysporum is a model multi-host pathogen, known to be associated with neuronal stress in humans and vascular wilt in plants. The interaction between innate immune and neuronal pathways is the basis of many diverse biological responses. How these processes are coordinated in response to fungal disease is not well understood...
2017: Cell Death Discovery
Mansour Sobeh, Mona F Mahmoud, Mohamed A O Abdelfattah, Haroan Cheng, Assem M El-Shazly, Michael Wink
ETHNOPHARMACOLOGICAL RELEVANCE: Cassia abbreviata is a small to medium sized branched umbrella-shaped deciduous tree. It is widely spread in the tropics, especially in Africa, having a long history in traditional medicine for the treatment of numerous conditions such as headaches, diarrhea, constipation, some skin diseases, malaria, syphilis, pneumonia, stomach troubles, uterine pains, and against gonorrhea. AIM OF THE STUDY: We investigated the phytochemical constituents of a root extract from Cassia abbreviata using HPLC-PDA-ESI-MS/MS...
March 1, 2018: Journal of Ethnopharmacology
Shamsuzzama, Lalit Kumar, Aamir Nazir
Neurodegenerative Parkinson's disease (PD) is a multi-factorial disorder lacking complete cure. Understanding the complete mechanism of initiation and progression of this disease has been quite challenging; however, progress has been made toward deciphering certain genetic aspects related to the disease condition. Genetics studies have provided clues toward the role of microRNAs (miRNAs) in various disease conditions. One of the crucial miRNA molecules, let-7, is highly conserved miRNA and is known to regulate important functions of development and viability; its altered expression has been reported in C...
2017: Frontiers in Molecular Neuroscience
Jonathan D Hibshman, Alexander E Doan, Brad T Moore, Rebecca Ew Kaplan, Anthony Hung, Amy K Webster, Dhaval P Bhatt, Rojin Chitrakar, Matthew D Hirschey, L Ryan Baugh
daf-16/FoxO is required to survive starvation in Caenorhabditis elegans, but how daf-16IFoxO promotes starvation resistance is unclear. We show that daf-16/FoxO restructures carbohydrate metabolism by driving carbon flux through the glyoxylate shunt and gluconeogenesis and into synthesis of trehalose, a disaccharide of glucose. Trehalose is a well-known stress protectant, capable of preserving membrane organization and protein structure during abiotic stress. Metabolomic, genetic, and pharmacological analyses confirm increased trehalose synthesis and further show that trehalose not only supports survival as a stress protectant but also serves as a glycolytic input...
October 24, 2017: ELife
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