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{"title"=>"Pro-aging effects of glucose signaling through a G protein-coupled glucose receptor in fission yeast", "type"=>"journal", "authors"=>[{"first_name"=>"Antoine E.", "last_name"=>"Roux", "scopus_author_id"=>"57197412470"}, {"first_name"=>"Alexandre", "last_name"=>"Leroux", "scopus_author_id"=>"25923428900"}, {"first_name"=>"Manal A.", "last_name"=>"Alaamery", "scopus_author_id"=>"24400909800"}, {"first_name"=>"Charles S.", "last_name"=>"Hoffman", "scopus_author_id"=>"35546828200"}, {"first_name"=>"Pascal", "last_name"=>"Chartrand", "scopus_author_id"=>"7005909097"}, {"first_name"=>"Gerardo", "last_name"=>"Ferbeyre", "scopus_author_id"=>"6701806770"}, {"first_name"=>"Luis A.", "last_name"=>"Rokeach", "scopus_author_id"=>"7004061863"}], "year"=>2009, "source"=>"PLoS Genetics", "identifiers"=>{"pmid"=>"19266076", "sgr"=>"62149091061", "doi"=>"10.1371/journal.pgen.1000408", "scopus"=>"2-s2.0-62149091061", "pui"=>"354404890", "isbn"=>"1553-7404 (Electronic)", "issn"=>"15537390"}, "id"=>"8e9f8a60-f2c2-3f62-8d9e-bdf487b80f91", "abstract"=>"Glucose is the preferred carbon and energy source in prokaryotes, unicellular eukaryotes, and metazoans. However, excess of glucose has been associated with several diseases, including diabetes and the less understood process of aging. On the contrary, limiting glucose (i.e., calorie restriction) slows aging and age-related diseases in most species. Understanding the mechanism by which glucose limits life span is therefore important for any attempt to control aging and age-related diseases. Here, we use the yeast Schizosaccharomyces pombe as a model to study the regulation of chronological life span by glucose. Growth of S. pombe at a reduced concentration of glucose increased life span and oxidative stress resistance as reported before for many other organisms. Surprisingly, loss of the Git3 glucose receptor, a G protein-coupled receptor, also increased life span in conditions where glucose consumption was not affected. These results suggest a role for glucose-signaling pathways in life span regulation. In agreement, constitutive activation of the Galpha subunit acting downstream of Git3 accelerated aging in S. pombe and inhibited the effects of calorie restriction. A similar pro-aging effect of glucose was documented in mutants of hexokinase, which cannot metabolize glucose and, therefore, are exposed to constitutive glucose signaling. The pro-aging effect of glucose signaling on life span correlated with an increase in reactive oxygen species and a decrease in oxidative stress resistance and respiration rate. Likewise, the anti-aging effect of both calorie restriction and the Deltagit3 mutation was accompanied by increased respiration and lower reactive oxygen species production. Altogether, our data suggest an important role for glucose signaling through the Git3/PKA pathway to regulate S. pombe life span.", "link"=>"http://www.mendeley.com/research/proaging-effects-glucose-signaling-through-g-proteincoupled-glucose-receptor-fission-yeast", "reader_count"=>87, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>4, "Researcher"=>20, "Student > Doctoral Student"=>3, "Student > Ph. D. Student"=>27, "Student > Postgraduate"=>6, "Student > Master"=>8, "Student > Bachelor"=>12, "Professor"=>6}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>4, "Researcher"=>20, "Student > Doctoral Student"=>3, "Student > Ph. D. Student"=>27, "Student > Postgraduate"=>6, "Student > Master"=>8, "Student > Bachelor"=>12, "Professor"=>6}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Environmental Science"=>1, "Biochemistry, Genetics and Molecular Biology"=>13, "Agricultural and Biological Sciences"=>69, "Medicine and Dentistry"=>1, "Computer Science"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>69}, "Computer Science"=>{"Computer Science"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>13}, "Unspecified"=>{"Unspecified"=>2}, "Environmental Science"=>{"Environmental Science"=>1}}, "reader_count_by_country"=>{"Sweden"=>1, "United States"=>4, "United Kingdom"=>1, "Mexico"=>1, "Australia"=>1, "Switzerland"=>1, "Germany"=>1, "India"=>1}, "group_count"=>2}

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• http://doi.org/10.1091/mbc.E19-03-0172
• http://doi.org/10.1007/s10528-011-9477-x
• http://doi.org/10.1016/j.exger.2010.03.014
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• http://doi.org/10.1111/acel.12080

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{"UNIPROT"=>4}

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Figshare

• {"files"=>["https://ndownloader.figshare.com/files/905836"], "description"=>"<p>(A) CLS of constitutively activated G protein mutant <i>gpa2^R176</i>^H and deletion of glucose receptor Git3p (<i>Δgit3</i>) in 2% glucose compared to wild type in 2% and 0.2% glucose. On the graphs, 2% and 0.2% refers to the concentration of glucose at the start of the culture. (B) β-Galactosidase activity of strain with <i>fbp1-lacZ</i> reporter whose expression is repressed by signaling via the Git3/PKA pathway. Cells were collected at late exponential phase and β-Gal activity was measured. (C) Accumulation of ROS-positive cells at day 4 of stationary phase in <i>Δgit3</i> and <i>gpa2^R176H</i> grown in 2% and 0.2% glucose. Data shown are mean±standard deviation of the mean of three independent samples assayed. •, <i>p</i><0.1; *, <i>p</i><0.02; **, <i>p</i><0.01, student test, WT versus mutant at the same glucose concentration.</p>", "links"=>[], "tags"=>["cls", "glucose", "requires", "signaling", "receptor"], "article_id"=>576282, "categories"=>["Cell Biology"], "users"=>["Antoine E. Roux", "Alexandre Leroux", "Manal A. Alaamery", "Charles S. Hoffman", "Pascal Chartrand", "Gerardo Ferbeyre", "Luis A. Rokeach"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1000408.g002", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Reduction_of_CLS_due_to_glucose_requires_signaling_via_the_glucose_receptor_and_G_protein_/576282", "title"=>"Reduction of CLS due to glucose requires signaling via the glucose receptor and G protein.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-03-06 01:44:42"}
• {"files"=>["https://ndownloader.figshare.com/files/448404", "https://ndownloader.figshare.com/files/448447", "https://ndownloader.figshare.com/files/448522", "https://ndownloader.figshare.com/files/448560", "https://ndownloader.figshare.com/files/448618", "https://ndownloader.figshare.com/files/448653", "https://ndownloader.figshare.com/files/448690"], "description"=>"<div><p>Glucose is the preferred carbon and energy source in prokaryotes, unicellular eukaryotes, and metazoans. However, excess of glucose has been associated with several diseases, including diabetes and the less understood process of aging. On the contrary, limiting glucose (i.e., calorie restriction) slows aging and age-related diseases in most species. Understanding the mechanism by which glucose limits life span is therefore important for any attempt to control aging and age-related diseases. Here, we use the yeast <em>Schizosaccharomyces pombe</em> as a model to study the regulation of chronological life span by glucose. Growth of <em>S. pombe</em> at a reduced concentration of glucose increased life span and oxidative stress resistance as reported before for many other organisms. Surprisingly, loss of the Git3 glucose receptor, a G protein-coupled receptor, also increased life span in conditions where glucose consumption was not affected. These results suggest a role for glucose-signaling pathways in life span regulation. In agreement, constitutive activation of the Gα subunit acting downstream of Git3 accelerated aging in <em>S. pombe</em> and inhibited the effects of calorie restriction. A similar pro-aging effect of glucose was documented in mutants of hexokinase, which cannot metabolize glucose and, therefore, are exposed to constitutive glucose signaling. The pro-aging effect of glucose signaling on life span correlated with an increase in reactive oxygen species and a decrease in oxidative stress resistance and respiration rate. Likewise, the anti-aging effect of both calorie restriction and the <em>Δgit3</em> mutation was accompanied by increased respiration and lower reactive oxygen species production. Altogether, our data suggest an important role for glucose signaling through the Git3/PKA pathway to regulate <em>S. pombe</em> life span.</p></div>", "links"=>[], "tags"=>["pro-aging", "effects", "glucose", "signaling", "protein-coupled", "receptor", "fission", "yeast"], "article_id"=>148359, "categories"=>["Cell Biology"], "users"=>["Antoine E. Roux", "Alexandre Leroux", "Manal A. Alaamery", "Charles S. Hoffman", "Pascal Chartrand", "Gerardo Ferbeyre", "Luis A. Rokeach"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1000408.s001", "https://dx.doi.org/10.1371/journal.pgen.1000408.s002", "https://dx.doi.org/10.1371/journal.pgen.1000408.s003", "https://dx.doi.org/10.1371/journal.pgen.1000408.s004", "https://dx.doi.org/10.1371/journal.pgen.1000408.s005", "https://dx.doi.org/10.1371/journal.pgen.1000408.s006", "https://dx.doi.org/10.1371/journal.pgen.1000408.s007"], "stats"=>{"downloads"=>0, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Pro_Aging_Effects_of_Glucose_Signaling_through_a_G_Protein_Coupled_Glucose_Receptor_in_Fission_Yeast/148359", "title"=>"Pro-Aging Effects of Glucose Signaling through a G Protein-Coupled Glucose Receptor in Fission Yeast", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2009-03-06 02:19:19"}
• {"files"=>["https://ndownloader.figshare.com/files/906210"], "description"=>"<p>Impairing glucose metabolism strongly decreases CLS and increases Git3/PKA signaling in late exponential phase cells. This pro-aging effect is lost when less glucose is provided. (A) CLS of WT and <i>Δhxk2</i> in low and high glucose concentration. (B) Glucose consumption according to growth in WT and <i>Δhxk2</i> cultured in 2% and 0.2% glucose. (C) β-Galactosidase activity of <i>Δhxk2</i> with <i>fbp1-lacZ</i> reporter. Cells were collected at late exponential phase and β-galactosidase activity was measured.</p>", "links"=>[], "tags"=>["mutant", "glucose", "signaling", "stationary"], "article_id"=>576660, "categories"=>["Cell Biology"], "users"=>["Antoine E. Roux", "Alexandre Leroux", "Manal A. Alaamery", "Charles S. Hoffman", "Pascal Chartrand", "Gerardo Ferbeyre", "Luis A. Rokeach"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1000408.g005", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Hexokinase_2_mutant_has_a_decreased_survival_and_an_increased_glucose_signaling_in_stationary_phase_/576660", "title"=>"Hexokinase 2 mutant has a decreased survival and an increased glucose signaling in stationary phase.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-03-06 01:51:00"}
• {"files"=>["https://ndownloader.figshare.com/files/906372"], "description"=>"<p>(A) Survival of <i>Δhxk1 Δhxk2</i> and <i>Δhxk1 Δhxk2 Δgit3</i> cells shifted from liquid culture with glycerol to solid media with glycerol, without or with glucose 0.2% or 2%. The growth of double hexokinase mutant on respiratory media plus glucose 2% is possible only with deleted Git3p-mediated signaling. 1 to 10⁴ represents the factors of dilution. (B) Quantification of living cells of <i>Δhxk1 Δhxk2</i> and <i>Δhxk1 Δhxk2 Δgit3</i> grown in respiratory media supplemented with glucose. The number of living cells per mL is calculated as the number of colony forming units on solid glycerol medium per mL of culture. Averages and standard deviations were calculated on three independent cultures. Left panel, <i>Δhxk1 Δhxk2</i>; right panel, <i>Δhxk1 Δhxk2 Δgit3</i>. (C) Microscopy analysis of double hexokinase mutants with vital dye Phloxin B applied 18 hours after glucose addition. The percentage under each picture represents the ratio of fluorescent cells counted under microscope on 500 cellules. (D) ROS production estimated by flow cytometry using DHE staining. This assay was carried out 36 hours after glucose addition. Left panel, increase of DHE staining was observed only in Δ<i>hxk1 Δhxk2</i> with glucose 2%, corresponding to premature aged cells. Right panel, summary of flow cytometry results of DHE-fluorescing cells (M2 population). In Δ<i>hxk1 Δhxk2</i>, 90% of the cells displayed about a 3 times greater fluorescence intensity between no glucose and glucose 2%. Three independent cultures were analysed for averages and standard deviations.</p>", "links"=>[], "tags"=>["glucose", "signaling", "aging"], "article_id"=>576823, "categories"=>["Cell Biology"], "users"=>["Antoine E. Roux", "Alexandre Leroux", "Manal A. Alaamery", "Charles S. Hoffman", "Pascal Chartrand", "Gerardo Ferbeyre", "Luis A. Rokeach"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1000408.g006", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Git3p_dependent_glucose_signaling_promotes_aging_in_the_absence_of_glucose_metabolism_/576823", "title"=>"Git3p-dependent glucose signaling promotes aging in the absence of glucose metabolism.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-03-06 01:53:43"}
• {"files"=>["https://ndownloader.figshare.com/files/906054"], "description"=>"<p>Longer chronological life span correlates with higher mitochondrial respiration and increased oxygen stress resistance, except with Gpa^R176H strain where loss of survival correlates only with weaker oxidative stress resistance. (A) CLS of <i>Δgit3</i> grown in 2% and 0.2% glucose as compared to wild type. (B) Chronological life span of <i>gpa2^R176H</i> grown in 2% and 0.2% glucose. (C) Oxidative stress resistance measured in WT, <i>Δgit3</i> and <i>gpa2^R176H</i> after short treatment of H₂O₂ and menadione. Cells were collected at day 1 of stationary phase and submitted to oxidative stressors before plating. (D) Oxidative stress resistance measured in WT and <i>gpa2^R176H</i> at weak dose of H₂O₂ and menadione. (E) Transcript levels of cytosolic and mitochondrial superoxide dismutase (SOD1 and 2) normalized to wild type cells as measured by quantitative RT-PCR. Total RNAs were isolated in cells collected at day one of stationary phase. The transcript levels were normalized on two constitutively expressed genes. Standard deviations were calculated on three independent experiments; student test was done comparing with wild type at glucose 2%. *, <i>p</i><0.01.</p>", "links"=>[], "tags"=>["longevity", "wt", "cr", "mutants", "glucose-signaling"], "article_id"=>576504, "categories"=>["Cell Biology"], "users"=>["Antoine E. Roux", "Alexandre Leroux", "Manal A. Alaamery", "Charles S. Hoffman", "Pascal Chartrand", "Gerardo Ferbeyre", "Luis A. Rokeach"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1000408.g004", "stats"=>{"downloads"=>0, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Correlation_between_longevity_and_stress_resistance_of_WT_S_pombe_in_CR_or_in_mutants_of_the_glucose_signaling_pathway_/576504", "title"=>"Correlation between longevity and stress resistance of WT <i>S. pombe</i> in CR or in mutants of the glucose-signaling pathway.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-03-06 01:48:24"}
• {"files"=>["https://ndownloader.figshare.com/files/905726"], "description"=>"<p>(A) Chronological life span of a wild type strain measured at different glucose concentrations in YEC by colony forming unit (CFU) counting. Percent on the graphs refers to the concentration of glucose. Survival (Y axis) is expressed as the ratio of the number of colonies at a given time-point on the number of colonies at the beginning of stationary phase (100%). (B) Morphology of wild type cells at glucose 2% and 0.2% observed under microscope by Nomarski at early exponential phase and stationary phase (day 8). (C) ROS measurements by DHR 123 staining in WT cells grown in 2% and 0.2% glucose. Yeast cells were stained at days 1 and 8 of the stationary phase, and analysed under microscope. (D) Quantitation of ROS-positive cells in WT cells grown in 2% and 0.2% glucose. Yeast cells were stained at days 1, 4 and 8 of the stationary phase and counted under microscope. Data shown are mean±standard deviation of the mean of three independent samples assayed. *, <i>p</i><0.02; **, <i>p</i><0.01, Student test, 2% glucose versus 0.2% glucose at a given day. (E) Chronological life span of wild type grown in SDC medium supplemented with glucose 2% or glycerol 3%.</p>", "links"=>[], "tags"=>["glucose"], "article_id"=>576179, "categories"=>["Cell Biology"], "users"=>["Antoine E. Roux", "Alexandre Leroux", "Manal A. Alaamery", "Charles S. Hoffman", "Pascal Chartrand", "Gerardo Ferbeyre", "Luis A. Rokeach"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1000408.g001", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Pro_aging_effects_of_glucose_in_S_pombe_/576179", "title"=>"Pro-aging effects of glucose in <i>S. pombe</i>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-03-06 01:42:59"}
• {"files"=>["https://ndownloader.figshare.com/files/906497"], "description"=>"<p>Glucose availability is sensed through two major pathways in fission yeast, the Git3/PKA pathway and the glucose repression pathway. Each of these pathways regulates mitochondrial functions. In the present study, we underlined the importance of Git3/PKA dependent signaling in longevity versus the glucose repression pathway and the metabolic effect of glycolysis. Git3/PKA signal inhibits mitochondrial respiration, oxidative stress response and promotes ROS formation and pro-aging phenotypes. Discontinuous line represents functions inferred by homology with <i>S. cerevisiae</i>. Question mark represents the possible role of mitochondria in aging besides ROS production.</p>", "links"=>[], "tags"=>["glucose-signaling", "pathway", "fission", "yeast"], "article_id"=>576946, "categories"=>["Cell Biology"], "users"=>["Antoine E. Roux", "Alexandre Leroux", "Manal A. Alaamery", "Charles S. Hoffman", "Pascal Chartrand", "Gerardo Ferbeyre", "Luis A. Rokeach"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1000408.g007", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_A_glucose_signaling_pathway_involved_in_fission_yeast_longevity_/576946", "title"=>"A glucose-signaling pathway involved in fission yeast longevity.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-03-06 01:55:46"}
• {"files"=>["https://ndownloader.figshare.com/files/905930"], "description"=>"<p>(A) Oxygen consumption measured using a Clark electrode for WT in low and high glucose, and for glucose receptor deleted strain <i>Δgit3</i>. Owt, Ogit3 represents the average of the oxygen consumption in exponential phase (calculated with OD₅₉₅<7 at 2% glucose and OD₅₉₅<2.1 at 0.2% glucose). (B) Growth of WT, <i>Δgit3</i> and <i>gpa2^R176H</i> switched from fermentative glucose medium to respiratory glycerol medium. (C) Oxygen consumption of <i>Δgit3</i> at 0.2% glucose as compared to wild type. (D) Oxygen consumption for constitutively active Gα subunit (<i>gpa2</i>^R176H) in low and high glucose as compared to WT. Ow_t, OGpa2* represents the average of the oxygen consumption in exponential phase (calculated with OD₅₉₅<7 at 2% glucose and OD₅₉₅<2.1 at 0.2% glucose).</p>", "links"=>[], "tags"=>["cr", "strains", "defects", "glucose"], "article_id"=>576383, "categories"=>["Cell Biology"], "users"=>["Antoine E. Roux", "Alexandre Leroux", "Manal A. Alaamery", "Charles S. Hoffman", "Pascal Chartrand", "Gerardo Ferbeyre", "Luis A. Rokeach"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1000408.g003", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Respiration_rate_is_increased_in_both_CR_and_in_strains_with_defects_in_glucose_signaling_/576383", "title"=>"Respiration rate is increased in both CR and in strains with defects in glucose signaling.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2009-03-06 01:46:23"}

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Relative Metric

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F1000Prime