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Kenneth Maiese
BACKGROUND: With the global increase in life span expectancy, neurodegenerative disorders continue to affect an ever increasing number of individuals throughout the world. New treatment strategies for neurodegenerative diseases are desperately required given the lack of current treatment modalities. METHODS: Here we examine novel strategies for neurodegenerative disorders that include circadian clock genes, non-coding ribonucleic acids (RNAs), and the mammalian forkhead transcription factors of the O class (FoxOs)...
March 19, 2018: Current Neurovascular Research
Yuan Li, Haisheng Wang, Fei Pei, Zhi Chen, Lu Zhang
INTRODUCTION: FoxO3a is a member of FoxO transcription factor family that participates in the transcriptional regulation of autophagy. In this study we explored the anti-inflammatory function of FoxO3a-regulated autophagy in inflamed human dental pulp and lipopolysaccharide-treated mDPC6T cells. METHODS: The expression of FoxO3a and autophagy markers in caries and pulpitis from human dental pulp were examined by immunohistochemistry and Western blot. We conducted in vitro studies by treating mDPC6T cells with lipopolysaccharide for various lengths of time...
March 15, 2018: Journal of Endodontics
Po-Han Chen, Jen-Tsan Chi, Michael Boyce
In metazoans, thousands of intracellular proteins are modified with O-linked β-N-acetylglucosamine (O-GlcNAc) in response to a wide range of stimuli and stresses. In particular, a complex and evolutionarily conserved interplay between O-GlcNAcylation and oxidative stress has emerged in recent years. Here, we review the current literature on the connections between O-GlcNAc and oxidative stress, with a particular emphasis on major signaling pathways, such as KEAP1/NRF2, FOXO, NFκB, p53 and cell metabolism...
March 14, 2018: Glycobiology
Silvia Parolo, Luca Marchetti, Mario Lauria, Karla Misselbeck, Marie-Pier Scott-Boyer, Laura Caberlotto, Corrado Priami
Although the genetic basis of Duchenne muscular dystrophy has been known for almost thirty years, the cellular and molecular mechanisms characterizing the disease are not completely understood and an efficacious treatment remains to be developed. In this study we analyzed proteomics data obtained with the SomaLogic technology from blood serum of a cohort of patients and matched healthy subjects. We developed a workflow based on biomarker identification and network-based pathway analysis that allowed us to describe different deregulated pathways...
2018: PloS One
Damla Tas, Luca Stickley, Federico Miozzo, Rafael Koch, Nicolas Loncle, Virginie Sabado, Bettina Gnägi, Emi Nagoshi
Forkhead box (FOXO) proteins are evolutionarily conserved, stress-responsive transcription factors (TFs) that can promote or counteract cell death. Mutations in FOXO genes are implicated in numerous pathologies, including age-dependent neurodegenerative disorders, such as Parkinson's disease (PD). However, the complex regulation and downstream mechanisms of FOXOs present a challenge in understanding their roles in the pathogenesis of PD. Here, we investigate the involvement of FOXO in the death of dopaminergic (DA) neurons, the key pathological feature of PD, in Drosophila...
March 12, 2018: PLoS Genetics
Jing Gao, Wei Nie, Fenglai Wang, Yuming Guo
The present study aimed to investigate the influence of maternal selenium supplementation on the skeletal muscle development of the offspring. A total of 720 Ross 308 broiler breeders at 24-week-old were allocated into 3 treatments with 6 replicates of 40 hens each and fed with 0 mg/kg-(group Se/C), 0.5 mg/kg organic-(group Se/O), and 0.5 mg/kg inorganic-(group Se/I) selenium, respectively for 8 weeks. The male offspring from each nutritional treatment were divided and housed into 8 cages of 12 birds each and fed with a commercial diet supplemented with selenium from Na2 SeO3 at 0...
March 9, 2018: Biological Trace Element Research
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
Hanlin Yao, Zhen Yao, Shaocheng Zhang, Wenjun Zhang, Wen Zhou
Osteoporosis is a disease that significantly influences life expectancy and quality in humans. Oxidative stress may stimulate bone marrow osteoclast differentiation and inhibit osteoblast (OB) differentiation. OB proliferation and differentiation are affected by the forkhead box O (FoxO)1/β‑catenin signaling pathway. The osteogenic differentiation of mesenchymal stem cells (MSCs) may be promoted by silent information regulator type‑1 [sirtuin (SIRT)1]. However, the molecular mechanism of SIRT1 regulation of osteogenic differentiation of MSCs remains unclear, and further elucidation is needed...
March 1, 2018: Molecular Medicine 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
Zhicheng Wang, Jun Cui, Jian Song, Haoze Wang, Kailun Gao, Xuemei Qiu, Meng Gou, Xin Li, Ziwen Hu, Xiuli Wang, Yaqing Chang
Heterosis is important for sea cucumber breeding, but its molecular mechanism remains largely unexplored. In this study, parental lines of Apostichopus japonicus from Russia (R) and China (C) were used to construct hybrids (CR and RC) by reciprocal crossing. We examined the transcriptional profiles of the hybrids (CR and RC) and the purebreds (CC and RR) at different developmental times. A total of 60.27 Gb of clean data was obtained, and 176,649 unigenes were identified, of which 50,312 unigenes were annotated...
February 28, 2018: Marine Biotechnology
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
François Lallemand, Ambre Petitalot, Sophie Vacher, Leanne de Koning, Karim Taouis, Bernard S Lopez, Sophie Zinn-Justin, Nicole Dalla-Venezia, Walid Chemlali, Anne Schnitzler, Rosette Lidereau, Ivan Bieche, Sandrine M Caputo
In mammals, FOXO transcriptional factors form a family of four members (FOXO1, 3, 4, and 6) involved in the modulation proliferation, apoptosis, and carcinogenesis. The role of the FOXO family in breast cancer remains poorly elucidated. According to the cellular context and the stage of the disease, FOXOs can have opposite effects on carcinogenesis. To study the role of FOXOs in breast carcinogenesis in more detail, we examined their expression in normal tissues, breast cell lines, and a large series of breast tumours of human origin...
January 26, 2018: Oncotarget
Tae Kawahara, Tomomi Kita, Yukako Ueno, Shojiro Yamasaki, Goh Kimura, Miki Nakanishi, Toshiyuki Hosokawa, Masaaki Kurasaki, Tajuddin Sikder, Takeshi Saito
Senescence-accelerated mice are known to display a variety of deficits and signs of accelerated aging, but the specific mechanisms involved in this process are still unclear. In this study, we examined the expression levels of antioxidant enzymes, transcription factors responsible for the regulation of expression of these enzymes, and mitochondrial proteins in the liver of SAMP10 and SAMR1 mice at 3 and 12 months of age using western blotting analysis. To investigate the amount of oxidative damage to DNA, levels of 8-OHdG were measured in the liver of these mice...
February 22, 2018: Experimental Gerontology
Wei-Sheng Lin, Sheng-Rong Yeh, Shou-Zen Fan, Liang-Yu Chen, Jui-Hung Yen, Tsai-Feng Fu, Ming-Shiang Wu, Pei-Yu Wang
Appropriate sexual selection or individual sexual attractiveness is closely associated with the reproductive success of a species. Here, we report that young male flies exhibit innate courtship preference for female flies that are raised on higher-yeast diets and that have greater body weight and fecundity, but reduced locomotor activity and shortened lifespan. Male flies discriminate among females that have been fed diets that contain 3 different yeast concentrations-1, 5, and 20% yeast- via gustatory, but not visual or olfactory, perception...
February 16, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Marta Di Martile, Marianna Desideri, Maria Grazia Tupone, Simonetta Buglioni, Barbara Antoniani, Carlotta Mastroiorio, Rita Falcioni, Virginia Ferraresi, Nicola Baldini, Roberto Biagini, Michele Milella, Daniela Trisciuoglio, Donatella Del Bufalo
Sarcomas are rare tumors with generally poor prognosis, for which current therapies have shown limited efficacy. Histone deacetylase inhibitors (HDACi) are emerging anti-tumor agents; however, little is known about their effect in sarcomas. By using established and patient-derived sarcoma cells with different subtypes, we showed that the pan-HDACi, ITF2357, potently inhibited in vitro survival in a p53-independent manner. ITF2357-mediated cell death implied the activation of mitochondrial apoptosis, as attested by induction of pro-apoptotic BH3-only proteins and a caspases-dependent mechanism...
February 23, 2018: Oncogenesis
Tokio Matsuzaki, Oscar Alvarez-Garcia, Sho Mokuda, Keita Nagira, Merissa Olmer, Ramya Gamini, Kohei Miyata, Yukio Akasaki, Andrew I Su, Hiroshi Asahara, Martin K Lotz
Aging is a main risk factor for osteoarthritis (OA). FoxO transcription factors protect against cellular and organismal aging, and FoxO expression in cartilage is reduced with aging and in OA. To investigate the role of FoxO in cartilage, Col2Cre-FoxO1, 3, and 4 single knockout (KO) and triple KO mice (Col2Cre-TKO) were analyzed. Articular cartilage in Col2Cre-TKO and Col2Cre-FoxO1 KO mice was thicker than in control mice at 1 or 2 months of age. This was associated with increased proliferation of chondrocytes of Col2Cre-TKO mice in vivo and in vitro...
February 14, 2018: Science Translational Medicine
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