Extension of Drosophila Lifespan by Rhodiola rosea through a Mechanism Independent from Dietary Restriction
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{"title"=>"Extension of Drosophila Lifespan by Rhodiola rosea through a Mechanism Independent from Dietary Restriction", "type"=>"journal", "authors"=>[{"first_name"=>"Samuel E.", "last_name"=>"Schriner", "scopus_author_id"=>"6506331989"}, {"first_name"=>"Kevin", "last_name"=>"Lee", "scopus_author_id"=>"55735190500"}, {"first_name"=>"Stephanie", "last_name"=>"Truong", "scopus_author_id"=>"55734446100"}, {"first_name"=>"Kathyrn T.", "last_name"=>"Salvadora", "scopus_author_id"=>"55985559800"}, {"first_name"=>"Steven", "last_name"=>"Maler", "scopus_author_id"=>"34977248800"}, {"first_name"=>"Alexander", "last_name"=>"Nam", "scopus_author_id"=>"55734667400"}, {"first_name"=>"Thomas", "last_name"=>"Lee", "scopus_author_id"=>"57198752513"}, {"first_name"=>"Mahtab", "last_name"=>"Jafari", "scopus_author_id"=>"7006582817"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"pmid"=>"23704949", "doi"=>"10.1371/journal.pone.0063886", "sgr"=>"84877995343", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "scopus"=>"2-s2.0-84877995343", "issn"=>"19326203", "pui"=>"368960551"}, "id"=>"302619fa-3ebc-377e-938f-8c5b50ff0aaf", "abstract"=>"Rhodiola rosea has been extensively used to improve physical and mental performance and to protect against stress. We, and others, have reported that R. rosea can extend lifespan in flies, worms, and yeast. However, its molecular mechanism is currently unknown. Here, we tested whether R. rosea might act through a pathway related to dietary restriction (DR) that can extend lifespan in a range of model organisms. While the mechanism of DR itself is also unknown, three molecular pathways have been associated with it: the silent information regulator 2 (SIR2) proteins, insulin and insulin-like growth factor signaling (IIS), and the target of rapamycin (TOR). In flies, DR is implemented through a reduction in dietary yeast content. We found that R. rosea extract extended lifespan in both sexes independent of the yeast content in the diet. We also found that the extract extended lifespan when the SIR2, IIS, or TOR pathways were genetically perturbed. Upon examination of water and fat content, we found that R. rosea decreased water content and elevated fat content in both sexes, but did not sensitize flies to desiccation or protect them against starvation. There were some sex-specific differences in response to R. rosea. In female flies, the expression levels of glycolytic genes and dSir2 were down-regulated, and NADH levels were decreased. In males however, R. rosea provided no protection against heat stress and had no effect on the major heat shock protein HSP70 and actually down-regulated the mitochondrial HSP22. Our findings largely rule out an elevated general resistance to stress and DR-related pathways as mechanistic candidates. The latter conclusion is especially relevant given the limited potential for DR to improve human health and lifespan, and presents R. rosea as a potential viable candidate to treat aging and age-related diseases in humans.", "link"=>"http://www.mendeley.com/research/extension-drosophila-lifespan-rhodiola-rosea-through-mechanism-independent-dietary-restriction", "reader_count"=>43, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>3, "Student > Doctoral Student"=>5, "Researcher"=>8, "Student > Ph. D. Student"=>10, "Student > Postgraduate"=>3, "Student > Master"=>6, "Other"=>3, "Student > Bachelor"=>3, "Lecturer"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>3, "Student > Doctoral Student"=>5, "Researcher"=>8, "Student > Ph. D. Student"=>10, "Student > Postgraduate"=>3, "Student > Master"=>6, "Other"=>3, "Student > Bachelor"=>3, "Lecturer"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>3, "Environmental Science"=>1, "Biochemistry, Genetics and Molecular Biology"=>2, "Medicine and Dentistry"=>4, "Agricultural and Biological Sciences"=>27, "Neuroscience"=>1, "Chemistry"=>1, "Psychology"=>1, "Computer Science"=>1, "Immunology and Microbiology"=>1, "Economics, Econometrics and Finance"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>4}, "Neuroscience"=>{"Neuroscience"=>1}, "Chemistry"=>{"Chemistry"=>1}, "Psychology"=>{"Psychology"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Economics, Econometrics and Finance"=>{"Economics, Econometrics and Finance"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>27}, "Computer Science"=>{"Computer Science"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}, "Unspecified"=>{"Unspecified"=>3}, "Environmental Science"=>{"Environmental Science"=>1}}, "reader_count_by_country"=>{"Canada"=>1, "Czech Republic"=>1, "Hungary"=>1, "United States"=>2, "Brazil"=>1, "France"=>1}, "group_count"=>3}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1065021"], "description"=>"<p>A and B. <i>R. rosea</i> feeding increased both mean lifespan and <b>C</b> and <b>D</b>, maximum lifespans in both sexes. The magnitude of mean lifespan increase for each dietary group are as follows: Males: 0.1%: 25%; 0.3%: 31%; 1%: 14%; 3%: 24%; 9%: 40%; Females: 0.1%: 16%; 0.3%: 16%; 1%: 13%; 3%: 24%; 9%: 36%. **<i>P</i><0.001, ***<i>P</i><0.0001, Mann-Whitney nonparametric test. Sample sizes for the control groups and treated groups respectively were as follows: Males: 0.1%: 120, 105; 0.3%: 112, 111; 1%: 110, 114; 3%: 116, 100; 9%: 99, 108; Females: 0.1%: 103, 121; 0.3%: 104, 112; 1%: 112, 105; 3%: 107, 122; 9%: 117, 121.</p>", "links"=>[], "tags"=>["Anatomy and physiology", "Physiological processes", "aging", "Biochemistry", "developmental biology", "Organism development", "Model organisms", "Animal models", "Drosophila melanogaster", "Molecular cell biology", "gene expression", "Complementary and alternative medicine", "lifespan", "dietary", "yeast"], "article_id"=>705512, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Samuel E. Schriner", "Kevin Lee", "Stephanie Truong", "Kathyrn T. Salvadora", "Steven Maler", "Alexander Nam", "Thomas Lee", "Mahtab Jafari"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0063886.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Extension_of_lifespan_by_Rhodiola_rosea_independent_of_dietary_yeast_content_/705512", "title"=>"Extension of lifespan by <i>Rhodiola rosea</i> independent of dietary yeast content.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-05-21 01:31:52"}
  • {"files"=>["https://ndownloader.figshare.com/files/1065022"], "description"=>"<p>A. <i>R. rosea</i> extended lifespan when TOR was inhibited, <i>P</i> = 0.003, n = 111 controls, 112 treated; <b>B</b>. the downstream S6 kinase was inhibited, <i>P</i><0.0001, n = 167 controls, 169 treated; and <b>C</b>. when S6 kinase was constitutively activated, <i>P</i><0.0001, n = 113 controls, 112 treated. The increases in mean lifespan due to <i>R. rosea</i> feeding were 17%, 19%, and 22%, respectively. <i>P</i>-values were calculated with the Mantel-Cox Log-Rank test.</p>", "links"=>[], "tags"=>["Anatomy and physiology", "Physiological processes", "aging", "Biochemistry", "developmental biology", "Organism development", "Model organisms", "Animal models", "Drosophila melanogaster", "Molecular cell biology", "gene expression", "Complementary and alternative medicine", "lifespan", "tor", "pathway"], "article_id"=>705513, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Samuel E. Schriner", "Kevin Lee", "Stephanie Truong", "Kathyrn T. Salvadora", "Steven Maler", "Alexander Nam", "Thomas Lee", "Mahtab Jafari"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0063886.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Extension_of_lifespan_by_Rhodiola_rosea_when_the_TOR_pathway_is_perturbed_/705513", "title"=>"Extension of lifespan by <i>Rhodiola rosea</i> when the TOR pathway is perturbed.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-05-21 01:31:53"}
  • {"files"=>["https://ndownloader.figshare.com/files/1065023"], "description"=>"<p><i>Rhodiola rosea</i> extended lifespan in the absence the insulin receptor substrate in both <b>A</b>, males, <i>P</i> = 0.004, and <b>B</b>, females, <i>P</i> = 0.0004. The extract also extended lifespan in the absence of the principal <i>Drosophila</i> Sir2 protein, dSIR2, in both <b>C</b>, males, <i>P</i><0.0001 and <b>D</b>, females, <i>P</i><0.05. <i>P</i>-values were calculated with the Mantel-Cox Log-Rank test. Increases in mean lifespan due to <i>R. rosea</i> feeding were as follows: <i>chico<sup>1</sup></i> males: 14%; <i>chico<sup>1</sup></i> females: 9%; <i>dSir2</i> males: 27%, <i>dSir2</i> females: 11%. Sample sizes for the control groups and treated groups respectively were as follows: <i>chico<sup>1</sup></i> males: 113, 114; <i>chico<sup>1</sup></i> females: 119, 118; <i>dSir2</i> males: 196, 193, <i>dSir2</i> females: 197, 191.</p>", "links"=>[], "tags"=>["Anatomy and physiology", "Physiological processes", "aging", "Biochemistry", "developmental biology", "Organism development", "Model organisms", "Animal models", "Drosophila melanogaster", "Molecular cell biology", "gene expression", "Complementary and alternative medicine", "lifespan", "sir2", "iis", "pathways"], "article_id"=>705514, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Samuel E. Schriner", "Kevin Lee", "Stephanie Truong", "Kathyrn T. Salvadora", "Steven Maler", "Alexander Nam", "Thomas Lee", "Mahtab Jafari"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0063886.g003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Rhodiola_rosea_extended_lifespan_when_the_SIR2_and_IIS_pathways_are_blocked_/705514", "title"=>"<i>Rhodiola rosea</i> extended lifespan when the SIR2 and IIS pathways are blocked.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-05-21 01:31:54"}
  • {"files"=>["https://ndownloader.figshare.com/files/1065025"], "description"=>"<p>A. The expression levels of 3 glycolytic genes, GAPDH1, enolase, and pyruvate kinase, were unaffected in males. <i>P</i>>0.05 for diet, two-way ANOVA. <b>B.</b> However, these 3 genes were all down-regulated in females. <i>P</i><0.001 for diet, two-way ANOVA. <b>C.</b> Pyruvate kinase enzyme activity is down regulated, approximately 20%, in females, but not males, consistent with our gene expression data. *<i>P</i><0.05, Students t test. <b>D.</b> Expression levels of <i>dSir2</i> were unaffected in males, but down-regulated in females. *<i>P</i><0.05, Students t test. Data are mean ± sem, n = 6 groups of 25 flies.</p>", "links"=>[], "tags"=>["Anatomy and physiology", "Physiological processes", "aging", "Biochemistry", "developmental biology", "Organism development", "Model organisms", "Animal models", "Drosophila melanogaster", "Molecular cell biology", "gene expression", "Complementary and alternative medicine", "glycolytic", "dsir2"], "article_id"=>705515, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Samuel E. Schriner", "Kevin Lee", "Stephanie Truong", "Kathyrn T. Salvadora", "Steven Maler", "Alexander Nam", "Thomas Lee", "Mahtab Jafari"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0063886.g004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_effect_of_Rhodiola_rosea_on_glycolytic_and_dSir2_gene_expression_in_w_1118_flies_/705515", "title"=>"The effect of <i>Rhodiola rosea</i> on glycolytic and dSir2 gene expression in <i>w<sup>1118</sup></i> flies.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-05-21 01:31:55"}
  • {"files"=>["https://ndownloader.figshare.com/files/1065026"], "description"=>"<p>A. Total NAD<sup>+</sup> content was unaffected by <i>R. rosea</i> feeding, however, <b>B.</b> NADH levels were significantly decreased in females, but not males given <i>R. rosea</i>. <b>C.</b> The ratio of NAD<sup>+</sup> and NADH, calculated from the values in panels A and B, are significantly elevated in females, but not males. Data are mean ± sem, n = 6. ***<i>P</i><0.0001 for interaction between sex and diet, two-way ANOVA, <i>P</i><0.001 between control and <i>R. rosea</i>-fed females, Bonferroni posttest. <i>Rhodiola rosea</i> feeding resulted in down-regulation of <b>D... </b><i>dilp2</i>, <i>P</i> = 0.001, <b>E... </b><i>dilp3</i>, <i>P</i><0.0001 and <b>F... </b><i>dilp5 P</i><0.0001, in both sexes. <i>P</i>-values are for diet, 2-way ANOVA, n = 6 groups of 25 flies for each bar. <b>G.</b> Soluble protein was decreased in females due to DR, but was unaffected by <i>R. rosea</i> feeding, <i>P</i><0.001. <b>H.</b> Fat content was unaffected by DR in males, but was elevated by DR in females, <i>P</i><0.001. <i>Rhodiola rosea</i> elevated fat content in both sexes, <i>P</i><0.001 for males, <i>P</i><0.05 for females. <b>I.</b> Water content was unaffected by DR, but was decreased by <i>R. rosea</i> in both sexes, <i>P</i><0.01 for males and <i>P</i><0.05 for females. <i>P</i>-values were calculated by Bonferroni posttests, 2-way ANOVA relative to the 3% yeast control group. For all experiments, n = 6 groups of 10–50 flies per bar.</p>", "links"=>[], "tags"=>["Anatomy and physiology", "Physiological processes", "aging", "Biochemistry", "developmental biology", "Organism development", "Model organisms", "Animal models", "Drosophila melanogaster", "Molecular cell biology", "gene expression", "Complementary and alternative medicine", "nadh"], "article_id"=>705516, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Samuel E. Schriner", "Kevin Lee", "Stephanie Truong", "Kathyrn T. Salvadora", "Steven Maler", "Alexander Nam", "Thomas Lee", "Mahtab Jafari"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0063886.g005"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_effect_of_Rhodiola_rosea_on_NAD_and_NADH_levels_dilp_expression_and_protein_fat_and_water_content_/705516", "title"=>"The effect of <i>Rhodiola rosea</i> on NAD<sup>+</sup> and NADH levels, <i>dilp</i> expression, and protein, fat, and water content.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-05-21 01:31:56"}
  • {"files"=>["https://ndownloader.figshare.com/files/1065027"], "description"=>"<p>A 2-week feeding of <i>R. rosea</i> had no ability to protect males or female flies against <b>A, B,</b> desiccation or <b>C, D,</b> starvation. <i>P</i>>0.05 for all groups. Mantel-Cox Log-Rank test. Sample sizes for the control groups and treated groups respectively were as follows: desiccation males: 114, 118; desiccation females: 94, 101; starvation males: 120, 118; starvation females: 120, 120. <b>E.. </b><i>Rhodiola rosea</i> did not protect males against exposure to 37°C, but did so in <b>F.</b> females, <i>P</i><0.0001, Mantel-Cox Log-Rank test. Sample sizes for the control groups and treated groups respectively were as follows: males: 120, 120; females: 120, 119. <b>G.. </b><i>Rhodiola rosea</i> had had no effect of HSP70 expression but <b>H.</b> down-regulated HSP22 in males, <i>P</i> = 0.004, Mann-Whitney nonparametric test, n = 5 groups of 25 flies for the controls and 6 groups of 25 flies for the treated flies.</p>", "links"=>[], "tags"=>["Anatomy and physiology", "Physiological processes", "aging", "Biochemistry", "developmental biology", "Organism development", "Model organisms", "Animal models", "Drosophila melanogaster", "Molecular cell biology", "gene expression", "Complementary and alternative medicine"], "article_id"=>705517, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Samuel E. Schriner", "Kevin Lee", "Stephanie Truong", "Kathyrn T. Salvadora", "Steven Maler", "Alexander Nam", "Thomas Lee", "Mahtab Jafari"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0063886.g006"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_effect_of_Rhodiola_rosea_on_the_tolerance_towards_starvation_desiccation_and_heat_/705517", "title"=>"The effect of <i>Rhodiola rosea</i> on the tolerance towards starvation, desiccation, and heat.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-05-21 01:31:57"}
  • {"files"=>["https://ndownloader.figshare.com/files/1065028", "https://ndownloader.figshare.com/files/1065029"], "description"=>"<div><p><i>Rhodiola rosea</i> has been extensively used to improve physical and mental performance and to protect against stress. We, and others, have reported that <i>R. rosea</i> can extend lifespan in flies, worms, and yeast. However, its molecular mechanism is currently unknown. Here, we tested whether <i>R. rosea</i> might act through a pathway related to dietary restriction (DR) that can extend lifespan in a range of model organisms. While the mechanism of DR itself is also unknown, three molecular pathways have been associated with it: the silent information regulator 2 (SIR2) proteins, insulin and insulin-like growth factor signaling (IIS), and the target of rapamycin (TOR). In flies, DR is implemented through a reduction in dietary yeast content. We found that <i>R. rosea</i> extract extended lifespan in both sexes independent of the yeast content in the diet. We also found that the extract extended lifespan when the SIR2, IIS, or TOR pathways were genetically perturbed. Upon examination of water and fat content, we found that <i>R. rosea</i> decreased water content and elevated fat content in both sexes, but did not sensitize flies to desiccation or protect them against starvation. There were some sex-specific differences in response to <i>R. rosea</i>. In female flies, the expression levels of glycolytic genes and <i>dSir2</i> were down-regulated, and NADH levels were decreased. In males however, <i>R. rosea</i> provided no protection against heat stress and had no effect on the major heat shock protein HSP70 and actually down-regulated the mitochondrial HSP22. Our findings largely rule out an elevated general resistance to stress and DR-related pathways as mechanistic candidates. The latter conclusion is especially relevant given the limited potential for DR to improve human health and lifespan, and presents <i>R. rosea</i> as a potential viable candidate to treat aging and age-related diseases in humans.</p></div>", "links"=>[], "tags"=>["Anatomy and physiology", "Physiological processes", "aging", "Biochemistry", "developmental biology", "Organism development", "Model organisms", "Animal models", "Drosophila melanogaster", "Molecular cell biology", "gene expression", "Complementary and alternative medicine", "lifespan", "dietary"], "article_id"=>705518, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Samuel E. Schriner", "Kevin Lee", "Stephanie Truong", "Kathyrn T. Salvadora", "Steven Maler", "Alexander Nam", "Thomas Lee", "Mahtab Jafari"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0063886.s001", "https://dx.doi.org/10.1371/journal.pone.0063886.s002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Extension_of_Drosophila_Lifespan_by_Rhodiola_rosea_through_a_Mechanism_Independent_from_Dietary_Restriction/705518", "title"=>"Extension of <i>Drosophila</i> Lifespan by <i>Rhodiola rosea</i> through a Mechanism Independent from Dietary Restriction", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2013-05-21 01:31:58"}

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Relative Metric

{"start_date"=>"2013-01-01T00:00:00Z", "end_date"=>"2013-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Biology and life sciences", "average_usage"=>[269, 466, 588, 697, 800, 896, 988, 1076, 1165, 1254, 1340, 1417]}, {"subject_area"=>"/Biology and life sciences/Biochemistry", "average_usage"=>[266, 468, 593, 703, 804, 903, 993, 1084, 1171, 1256, 1339, 1422, 1492]}, {"subject_area"=>"/Biology and life sciences/Cell biology", "average_usage"=>[272, 472, 600, 713, 815, 911, 1004, 1094, 1185, 1273, 1358, 1441]}, {"subject_area"=>"/Biology and life sciences/Nutrition", "average_usage"=>[264, 463, 602, 708, 816, 908, 1015, 1103, 1200, 1297, 1389, 1476, 1538]}, {"subject_area"=>"/Medicine and health sciences/Endocrinology", "average_usage"=>[255, 447, 575, 680, 781, 872, 965, 1055, 1143, 1236, 1317, 1397, 1457]}, {"subject_area"=>"/Medicine and health sciences/Nutrition", "average_usage"=>[273, 476, 611, 714, 821, 911, 1005, 1103, 1201, 1287, 1388, 1478, 1557]}]}
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