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Gladyshev, Vadim

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Gladyshev

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Gladyshev, Vadim
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Now showing 1 - 10 of 54
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    Methionine restriction extends lifespan of Drosophila melanogaster under conditions of low amino acid status
    (2014) Lee, Byung Cheon; Kaya, Alaattin; Ma, Siming; Kim, Gwansu; Gerashchenko, Maxim; Yim, Sun Hee; Hu, Zhen; Harshman, Lawrence G.; Gladyshev, Vadim
    Reduced methionine (Met) intake can extend lifespan of rodents, but whether this regimen represents a general strategy for regulating aging has been controversial. Here we report that Met restriction extends lifespan in both fruit flies and yeast, and that this effect requires low amino acid status. Met restriction in Drosophila mimicks the effect of dietary restriction and is associated with decreased reproduction. However, under conditions of high amino acid status, Met restriction is ineffective and the trade-off between longevity and reproduction is not observed. Overexpression of InRDN or Tsc2 inhibits lifespan extension by Met restriction, suggesting the role of TOR signaling in the Met control of longevity. Overall, this study defines the specific roles of Met and amino acid imbalance in aging and suggests that Met restiction is a general strategy for lifespan extension.
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    A review of the biomedical innovations for healthy longevity
    (Impact Journals LLC, 2017) Moskalev, Alexey; Anisimov, Vladimir; Aliper, Aleksander; Artemov, Artem; Asadullah, Khusru; Belsky, Daniel; Baranova, Ancha; de Grey, Aubrey; Dixit, Vishwa Deep; Debonneuil, Edouard; Dobrovolskaya, Eugenia; Fedichev, Peter; Fedintsev, Alexander; Fraifeld, Vadim; Franceschi, Claudio; Freer, Rosie; Fülöp, Tamas; Feige, Jerome; Gems, David; Gladyshev, Vadim; Gorbunova, Vera; Irincheeva, Irina; Jager, Sibylle; Jazwinski, S. Michal; Kaeberlein, Matt; Kennedy, Brian; Khaltourina, Daria; Kovalchuk, Igor; Kovalchuk, Olga; Kozin, Sergey; Kulminski, Alexander; Lashmanova, Ekaterina; Lezhnina, Ksenia; Liu, Guang Hui; Longo, Valter; Mamoshina, Polina; Maslov, Alexander; de Magalhaes, Joao Pedro; Mitchell, James; Mitnitski, Arnold; Nikolsky, Yuri; Ozerov, Ivan; Pasyukova, Elena; Peregudova, Darya; Popov, Vasily; Proshkina, Ekaterina; Putin, Evgeny; Rogaev, Evgeny; Rogina, Blanka; Schastnaya, Jane; Seluanov, Andrey; Shaposhnikov, Mikhail; Simm, Andreas; Skulachev, Vladimir; Skulachev, Maxim; Solovev, Ilya; Spindler, Stephen; Stefanova, Natalia; Suh, Yousin; Swick, Andrew; Tower, John; Gudkov, Andrei V.; Vijg, Jan; Voronkov, Andrey; West, Michael; Wagner, Wolfgang; Yashin, Anatoliy; Zemskaya, Nadezhda; Zhumadilov, Zhaxybay; Zhavoronkov, Alex
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    The Insertion Green Monster (iGM) Method for Expression of Multiple Exogenous Genes in Yeast
    (Genetics Society of America, 2014) Labunskyy, Vyacheslav M.; Suzuki, Yo; Hanly, Timothy J.; Murao, Ayako; Roth, Frederick P.; Gladyshev, Vadim
    Being a simple eukaryotic organism, Saccharomyces cerevisiae provides numerous advantages for expression and functional characterization of proteins from higher eukaryotes, including humans. However, studies of complex exogenous pathways using yeast as a host have been hampered by the lack of tools to engineer strains expressing a large number of genetic components. In addition to inserting multiple genes, it is often desirable to knock out or replace multiple endogenous genes that might interfere with the processes studied. Here, we describe the “insertion Green Monster” (iGM) set of expression vectors that enable precise insertion of many heterologous genes into the yeast genome in a rapid and reproducible manner and permit simultaneous replacement of selected yeast genes. As a proof of principle, we have used the iGM method to replace components of the yeast pathway for methionine sulfoxide reduction with genes encoding the human selenoprotein biosynthesis machinery and generated a single yeast strain carrying 11 exogenous components of the selenoprotein biosynthetic pathway in precisely engineered loci.
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    Cell Proliferation and Motility Are Inhibited by G1 Phase Arrest in 15-kDa Selenoprotein-Deficient Chang Liver Cells
    (Korean Society for Molecular and Cellular Biology, 2015) Bang, Jeyoung; Huh, Jang Hoe; Na, Ji-Woon; Lu, Qiao; Carlson, Bradley A.; Tobe, Ryuta; Tsuji, Petra A.; Gladyshev, Vadim; Hatfield, Dolph L.; Lee, Byeong Jae
    The 15-kDa selenoprotein (Sep15) is a selenoprotein residing in the lumen of the endoplasmic reticulum (ER) and implicated in quality control of protein folding. Herein, we established an inducible RNAi cell line that targets Sep15 mRNA in Chang liver cells. RNAi-induced Sep15 deficiency led to inhibition of cell proliferation, whereas cell growth was resumed after removal of the knockdown inducer. Sep15-deficient cells were arrested at the G1 phase by upregulating p21 and p27, and these cells were also characterized by ER stress. In addition, Sep15 deficiency led to the relocation of focal adhesions to the periphery of the cell basement and to the decrease of the migratory and invasive ability. All these changes were reversible depending on Sep15 status. Rescuing the knockdown state by expressing a silent mutant Sep15 mRNA that is resistant to siRNA also reversed the phenotypic changes. Our results suggest that SEP15 plays important roles in the regulation of the G1 phase during the cell cycle as well as in cell motility in Chang liver cells, and that this selenoprotein offers a novel functional link between the cell cycle and cell motility.
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    The Second International Conference “Genetics of Aging and Longevity”
    (Impact Journals LLC, 2012) Anisimov, Vladimir N.; Bartke, Andrzej; Barzilai, Nir; Batin, Mikhail A.; Blagosklonny, Mikhail V.; Brown-Borg, Holly; Budovskaya, Yelena; Campisi, Judith; Friguet, Bertrand; Fraifeld, Vadim; Franceschi, Claudio; Gems, David; Gladyshev, Vadim; Gorbunova, Vera; Gudkov, Andrei V.; Kennedy, Brian; Konovalenko, Maria; Kraemer, Brian; Moskalev, Alexey; Petropoulos, Isabelle; Pasyukova, Elena; Rattan, Suresh; Rogina, Blanka; Seluanov, Andrei; Shaposhnikov, Mikhail; Reis, Robert Shmookler; Tavernarakis, Nektarios; Vijg, Jan; Yashin, Anatoli; Zimniak, Piotr
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    Expression of the methionine sulfoxide reductase lost during evolution extends Drosophila lifespan in a methionine-dependent manner
    (Nature Publishing Group UK, 2018) Lee, Byung Cheon; Lee, Hae Min; Kim, Sorah; Avanesov, Andrei S.; Lee, Aro; Chun, Bok-Hwan; Vorbruggen, Gerd; Gladyshev, Vadim
    Accumulation of oxidized amino acids, including methionine, has been implicated in aging. The ability to reduce one of the products of methionine oxidation, free methionine-R-sulfoxide (Met-R-SO), is widespread in microorganisms, but during evolution this function, conferred by the enzyme fRMsr, was lost in metazoa. We examined whether restoration of the fRMsr function in an animal can alleviate the consequences of methionine oxidation. Ectopic expression of yeast fRMsr supported the ability of Drosophila to catalyze free Met-R-SO reduction without affecting fecundity, food consumption, and response to starvation. fRMsr expression also increased resistance to oxidative stress. Moreover, it extended lifespan of flies in a methionine-dependent manner. Thus, expression of an oxidoreductase lost during evolution can enhance metabolic and redox functions and lead to an increase in lifespan in an animal model. More broadly, our study exposes the potential of a combination of genetic and nutritional strategies in lifespan control.
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    Genome-Wide RNAi Ionomics Screen Reveals New Genes and Regulation of Human Trace Element Metabolism
    (2017) Malinouski, Mikalai; Hasan, Nesrin M.; Zhang, Yan; Seravalli, Javier; Lin, Jie; Avanesov, Andrei S.; Lutsenko, Svetlana; Gladyshev, Vadim
    Trace elements are essential for human metabolism and dysregulation of their homeostasis is associated with numerous disorders. Here we characterize mechanisms that regulate trace elements in human cells by designing and performing a genome-wide high-throughput siRNA/ionomics screen, and examining top hits in cellular and biochemical assays. The screen reveals high stability of the ionomes, especially the zinc ionome, and yields known regulators and novel candidates. We further uncover fundamental differences in the regulation of different trace elements. Specifically, selenium levels are controlled through the selenocysteine machinery and expression of abundant selenoproteins; copper balance is affected by lipid metabolism and requires machinery involved in protein trafficking and posttranslational modifications; and the iron levels are influenced by iron import and expression of the iron/heme-containing enzymes. Our approach can be applied to a variety of disease models and/or nutritional conditions, and the generated dataset opens new directions for studies of human trace element metabolism.
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    Global remodeling of the mouse DNA methylome during aging and in response to calorie restriction
    (John Wiley and Sons Inc., 2018) Sziráki, András; Tyshkovskiy, Alexander; Gladyshev, Vadim
    Summary Aging is characterized by numerous molecular changes, such as accumulation of molecular damage and altered gene expression, many of which are linked to DNA methylation. Here, we characterize the blood DNA methylome across 16 age groups of mice and report numerous global, region‐ and site‐specific features, as well as the associated dynamics of methylation changes. Transition of the methylome throughout lifespan was not uniform, with many sites showing accelerated changes in late life. The associated genes and promoters were enriched for aging‐related pathways, pointing to a fundamental link between DNA methylation and control of the aging process. Calorie restriction both shifted the overall methylation pattern and was accompanied by its gradual age‐related remodeling, the latter contributing to the lifespan‐extending effect. With age, both highly and poorly methylated sites trended toward intermediate levels, and aging was accompanied by an accelerated increase in entropy, consistent with damage accumulation. However, the entropy effects differed for the sites that increased, decreased and did not change methylation with age. Many sites trailed behind, whereas some followed or even exceeded the entropy trajectory and altered the developmental DNA methylation pattern. The patterns we observed in certain genomic regions were conserved between humans and mice, suggesting common principles of functional DNA methylome remodeling and its critical role in aging. The highly resolved DNA methylome remodeling provides an excellent model for understanding systemic changes that characterize the aging process.
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    Naked Mole Rat Induced Pluripotent Stem Cells and Their Contribution to Interspecific Chimera
    (Elsevier, 2017) Lee, Sang-Goo; Mikhalchenko, Aleksei E.; Yim, Sun Hee; Lobanov, Alexei V.; Park, Jin-Kyu; Choi, Kwang-Hwan; Bronson, Roderick; Lee, Chang-Kyu; Park, Thomas J.; Gladyshev, Vadim
    Summary Naked mole rats (NMRs) are exceptionally long-lived, cancer-resistant rodents. Identifying the defining characteristics of these traits may shed light on aging and cancer mechanisms. Here, we report the generation of induced pluripotent stem cells (iPSCs) from NMR fibroblasts and their contribution to mouse-NMR chimeric embryos. Efficient reprogramming could be observed under N2B27+2i conditions. The iPSCs displayed a characteristic morphology, expressed pluripotent markers, formed embryoid bodies, and showed typical differentiation patterns. Interestingly, NMR embryonic fibroblasts and the derived iPSCs had propensity for a tetraploid karyotype and were resistant to forming teratomas, but within mouse blastocysts they contributed to both interspecific placenta and fetus. Gene expression patterns of NMR iPSCs were more similar to those of human than mouse iPSCs. Overall, we uncovered unique features of NMR iPSCs and report a mouse-NMR chimeric model. The iPSCs and associated cell culture systems can be used for a variety of biological and biomedical applications.
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    Molecular Footprints of Aquatic Adaptation Including Bone Mass Changes in Cetaceans
    (Oxford University Press, 2018) Zhou, Xuming; Sun, Di; Guang, Xuanmin; Ma, Siming; Fang, Xiaodong; Mariotti, Marco; Nielsen, Rasmus; Gladyshev, Vadim; Yang, Guang
    Abstract Cetaceans (whales, dolphins, and porpoises) are a group of specialized mammals that evolved from terrestrial ancestors and are fully adapted to aquatic habitats. Taking advantage of the recently sequenced finless porpoise genome, we conducted comparative analyses of the genomes of seven cetaceans and related terrestrial species to provide insight into the molecular bases of adaptation of these aquatic mammals. Changes in gene sequences were identified in main lineages of cetaceans, offering an evolutionary picture of cetacean genomes that reveal new pathways that could be associated with adaptation to aquatic lifestyle. We profiled bone microanatomical structures across 28 mammals, including representatives of cetaceans, pinnipeds, and sirenians. Subsequent phylogenetic comparative analyses revealed genes (including leptin, insulin-like growth factor 1, and collagen type I alpha 2 chain) with the root-to-tip substitution rate significantly correlated with bone compactness, implicating these genes could be involved in bone mass control. Overall, this study described adjustments of the genomes of cetaceans according to lifestyle, phylogeny, and bone mass.