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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
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
Cong Lan, Xinjian Chen, Yuxun Zhang, Wei Wang, Wei Eric Wang, Yukai Liu, Yue Cai, Hongmei Ren, Shuo Zheng, Lin Zhou, Chunyu Zeng
BACKGROUND: Antioxidants have shown great promise in stroke prevention. Diarylheptanoids (also known as diphenylheptanoids) are a small class of plant secondary metabolites that possess antioxidant activity greater than that of α-tocopherol. Curcumin is the best known member and is mainly extracted from turmeric. This study aimed to explore whether curcumin has a preventive effect on stroke. METHODS: Stroke-prone spontaneously hypertensive rats (SHRsp) were randomly divided into control group (n = 10) and curcumin group (n = 10), and saline or curcumin (100 mg/kg/day) was administrated daily...
March 1, 2018: BMC Cardiovascular Disorders
Nicole M Templeman, Shijing Luo, Rachel Kaletsky, Cheng Shi, Jasmine Ashraf, William Keyes, Coleen T Murphy
A decline in female reproduction is one of the earliest hallmarks of aging in many animals, including invertebrates and mammals [1-4]. The insulin/insulin-like growth factor-1 signaling (IIS) pathway has a conserved role in regulating longevity [5] and also controls reproductive aging [2, 6]. Although IIS transcriptional targets that regulate somatic aging have been characterized [7, 8], it was not known whether the same mechanisms influence reproductive aging. We previously showed that Caenorhabditis elegans daf-2 IIS receptor mutants extend reproductive span by maintaining oocyte quality with age [6], but IIS targets in oocytes had not been identified...
February 22, 2018: Current Biology: CB
Vinicius Guzzoni, Tatiana Sousa Cunha, Vander José das Neves, Larissa Briet, Rafaela Costa, Maria José Costa Sampaio Moura, Vanessa Oliveira, Maria do Carmo Pinho Franco, Pedro Duarte Novaes, Fernanda Klein Marcondes
Anabolic Androgenic Steroids (AASs) misuse has increased among adolescents and recreational athletes due to their potential effects on muscle hypertrophy. On the other hand, AAS might induce alterations on cardiovascular system, although some controversies regarding AAS on vascular properties remain unknown. To address this question, we aimed to investigate the effects of high doses of nandrolone combined with strenuous resistance training (RT) on function and structure of thoracic aorta. Rats were randomized into four groups: non-trained vehicle (NTV), trained vehicle (TV), non-trained nandrolone (NTN), and trained nandrolone (TN), and submitted to 6 weeks of treatment with nandrolone (5mg/kg, twice a week) and/or resistance training...
January 6, 2018: Steroids
Adeline Mergoud Dit Lamarche, Laurent Molin, Laura Pierson, Marie-Christine Mariol, Jean-Louis Bessereau, Kathrin Gieseler, Florence Solari
Aging is commonly defined as the loss of global homeostasis, which results from progressive alteration of all organs function. This model is currently challenged by recent data showing that interventions that extend lifespan do not always increase the overall fitness of the organism. These data suggest the existence of tissue-specific factors that regulate the pace of aging in a cell-autonomous manner. Here, we investigated aging of Caenorhabditis elegans striated muscles at the subcellular and the physiological level...
January 3, 2018: Aging Cell
Yohei Matsunaga, Toshiya Matsukawa, Takashi Iwasaki, Koji Nagata, Tsuyoshi Kawano
In Caenorhabditis elgans, insulin-like peptides have significant roles in modulating larval diapause and adult lifespan via the insulin/IGF-1 signaling (IIS) pathway. Although 40 insulin-like peptides (ILPs) have been identified, it remains unknown how ILPs act as either agonists or antagonists for their sole receptor, DAF-2. Here we found 1) INS-23 functions as an antagonistic ILP to promote larval diapause through the IIS pathway like a DAF-2 antagonist, INS-18, 2) INS-23 and INS-18 have similar biochemical functions...
January 5, 2018: Bioscience, Biotechnology, and Biochemistry
Yoshinori Haraguchi, Yoshito Mizoguchi, Masahiro Ohgidani, Yoshiomi Imamura, Toru Murakawa-Hirachi, Hiromi Nabeta, Hiroshi Tateishi, Takahiro A Kato, Akira Monji
BACKGROUND: Microglia are resident innate immune cells which release many factors including proinflammatory cytokines or nitric oxide (NO) when they are activated in response to immunological stimuli. Pathophysiology of Alzheimer's disease (AD) is related to the inflammatory responses mediated by microglia. Intracellular Ca2+ signaling is important for microglial functions such as release of NO and cytokines. In addition, alteration of intracellular Ca2+ signaling underlies the pathophysiology of AD, while it remains unclear how donepezil, an acetylcholinesterase inhibitor, affects intracellular Ca2+ mobilization in microglial cells...
December 22, 2017: Journal of Neuroinflammation
Julie Dagenhardt, Angeline Trinh, Halen Sumner, Jeffrey Scott, Eric Aamodt, Donard S Dwyer
Defects in insulin signaling have been reported in schizophrenia and major depressive disorder, which also share certain negative symptoms such as avolition, anhedonia, and apathy. These symptoms reflect diminished motivational states, which have been modeled in rodents as increased immobility in the forced swimming test. We have discovered that loss-of-function mutations in the insulin receptor ( daf-2 ) and syntaxin ( unc-64 ) genes in Caenorhabditis elegans , brief food deprivation, and exposure to DMSO produce immobility and avolition in non-dauer adults...
November 2017: Molecular Neuropsychiatry
Fujie Yan, Xin'an Chen, Xiaodong Zheng
Type 2 diabetes is a chronic disease and hyperglycemia is important in the pathogenesis of diabetic complications. Exposure of LO2 cells to high glucose resulted in cellular glucose consumption and uptake decreases, reactive oxygen species (ROS) and superoxide anion (O2 - ) accumulation and mitochondrial dysfunction, which could be partly recovered by mulberry anthocyanin extract (MAE). And these protective effects were partly associated with regulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream targets...
December 2017: Food Research International
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
Joshua Coulter Russell, Nikolay Burnaevskiy, Bridget Ma, Miguel Arenas Mailig, Franklin Faust, Matt Crane, Matt Kaeberlein, Alexander Mendenhall
The function of the pharynx, an organ in the model system Caenorhabditis elegans, has been correlated with lifespan and motility (another measure of health) since 1980. In this study, in order to further understand the relationship between organ function and lifespan, we measured the age-related decline of the pharynx using an electrophysiological approach. We measured and analyzed electropharyngeograms of wild type animals, short-lived hsf-1 mutants, and long-lived animals with genetically decreased insulin signaling or increased heat shock pathway signaling; we recorded a total of 2,478 electropharyngeograms from 1,374 individuals...
November 18, 2017: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
Sheena Maharaj, Kim D Lu, Shlomit Radom-Aizik, Frank Zaldivar, Fadia Haddad, Hye-Won Shin, Szu-Yun Leu, Eliezer Nussbaum, Inderpal Randhawa, Dan M Cooper
Assessment of nitric oxide (NO) dynamics in immune cells, commonly measured using NO surrogates such as inducible nitric oxide synthase (iNOS) rather than NO itself, has been effective in understanding pathophysiology across a wide range of diseases. Although the intracellular measurement of NO is now feasible, many technical issues remain unresolved. The principle aim of our study was to determine the effect of storage time of whole blood on nitric oxide (NO) level expression in leukocytes. This is important because immune cells remain chemically dynamic even after they are removed from the circulation, and the impact of storage time must be known to optimally quantify the effect of a disease or condition on NO dynamics in circulating leukocytes...
January 30, 2018: Nitric Oxide: Biology and Chemistry
Lingtong Zhi, Yonglin Yu, Zhixia Jiang, Dayong Wang
We performed a systematic identification of microRNAs (miRNAs) involved in the control of innate immunity. We identified 7 novel miRNA mutants with altered survival, colony forming in the body, and expression pattern of putative antimicrobial genes after Pseudomonas aeruginosa infection. Loss-of-function mutation of mir-45, mir-75, mir-246, mir-256, or mir-355 induced resistance to P. aeruginosa infection, whereas loss-of-function mutation of mir-63 or mir-360 induced susceptibility to P. aeruginosa infection...
November 6, 2017: Scientific Reports
Wojciech Pokrzywa, Robin Lorenz, Thorsten Hoppe
The integrity of the cellular proteome is supported by quality control networks, which govern protein synthesis, folding, and degradation. It is generally accepted that an age-related decline in protein homeostasis (proteostasis) contributes to protein aggregation diseases. However, the mechanistic principles underlying proteostasis imbalance and the impact on life expectancy are not well understood. We recently demonstrated that this interrelation is affected by chaperone-directed ubiquitylation, shifting the amount of the conserved DAF-2/insulin receptor both in Caenorhabditis elegans and Drosophila melanogaster...
2017: Worm
Agnes Keszler, Brian Lindemer, Dorothee Weihrauch, Deron Jones, Neil Hogg, Nicole L Lohr
Peripheral artery disease (PAD) is a morbid condition whereby ischemic peripheral muscle causes pain and tissue breakdown. Interestingly, PAD risk factors, e.g. diabetes mellitus, cause endothelial dysfunction secondary to decreased nitric oxide (NO) levels, which could explain treatment failures. Previously, we demonstrated 670nm light (R/NIR) increased NO from nitrosyl-heme stores, therefore we hypothesized R/NIR can stimulate vasodilation in healthy and diabetic blood vessels. Vasodilation was tested by ex vivo pressure myography in wild type C57Bl/6, endothelial nitric oxide synthase (eNOS) knockout, and db/db mice (10mW/cm2 for 5min with 10min dark period)...
December 2017: Free Radical Biology & Medicine
Collin Yvès Ewald, Jorge Iván Castillo-Quan, T Keith Blackwell
The groundbreaking discovery that lower levels of insulin/IGF-1 signaling (IIS) can induce lifespan extension was reported 24 years ago in the nematode Caenorhabditis elegans. In this organism, mutations in the insulin/IGF-1 receptor gene daf-2 or other genes in this pathway can double lifespan. Subsequent work has revealed that reduced IIS (rIIS) extends lifespan across diverse species, possibly including humans. In C. elegans, IIS also regulates development into the diapause state known as dauer, a quiescent larval form that enables C...
September 22, 2017: Gerontology
Verónica García-Morales, María Luaces-Regueira, Manuel Campos-Toimil
3',5'-Cyclic adenosine monophosphate (cAMP) exerts an endothelium-dependent vasorelaxant action by stimulating endothelial NO synthase (eNOS) activity, and the subsequent NO release, through cAMP protein kinase (PKA) and exchange protein directly activated by cAMP (Epac) activation in endothelial cells. Here, we have investigated the mechanism by which the cAMP-Epac/PKA pathway activates eNOS. cAMP-elevating agents (forskolin and dibutyryl-cAMP) and the joint activation of PKA (6-Bnz-cAMP) and Epac (8-pCPT-2'-O-Me-cAMP) increased cytoplasmic Ca2+ concentration ([Ca2+ ]c ) in ≤30% of fura-2-loaded isolated human umbilical vein endothelial cells (HUVEC)...
December 1, 2017: Biochemical Pharmacology
Dejuan Zhi, Dong Wang, Wenqi Yang, Ziyun Duan, Shuqian Zhu, Juan Dong, Na Wang, Ningbo Wang, Dongqing Fei, Zhanxin Zhang, Xin Wang, Meizhu Wang, Hongyu Li
Dianxianning (DXN) is a traditional Chinese formula, and has been approved in China for treating epilepsy since 1996. Here anti-Alzheimer's disease activity of DXN has been reported. DXN improved AD-like symptoms of paralysis and 5-HT sensitivity of transgenic Aβ1-42 C. elegans. In worms, DXN significantly increased Aβ monomers and decreased the toxic Aβ oligomers, thus reducing Aβ toxicity. DXN significantly suppressed the expression of hsp-16.2 induced by juglone, and up-regulated sod-3 expression. These results indicated that DXN increased stress resistance and protected C...
September 12, 2017: Scientific Reports
N J Palmisano, N Rosario, M Wysocki, M Hong, B Grant, A Meléndez
Macroautophagy/autophagy involves the formation of an autophagosome, a double-membrane vesicle that delivers sequestered cytoplasmic cargo to lysosomes for degradation and recycling. Closely related, endocytosis mediates the sorting and transport of cargo throughout the cell, and both processes are important for cellular homeostasis. However, how endocytic proteins functionally intersect with autophagy is not clear. Mutations in the DAF-2/insulin-like IGF-1 (INSR) receptor at the permissive temperature result in a small increase in GFP::LGG-1 foci, i...
October 3, 2017: Autophagy
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