A Role for Autophagy in the Extension of Lifespan by Dietary Restriction in C. elegans
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{"title"=>"A role for autophagy in the extension of lifespan by dietary restriction in C. elegans", "type"=>"journal", "authors"=>[{"first_name"=>"Malene", "last_name"=>"Hansen", "scopus_author_id"=>"7401874111"}, {"first_name"=>"Abha", "last_name"=>"Chandra", "scopus_author_id"=>"16400741100"}, {"first_name"=>"Laura L.", "last_name"=>"Mitic", "scopus_author_id"=>"57190069016"}, {"first_name"=>"Brian", "last_name"=>"Onken", "scopus_author_id"=>"6602983695"}, {"first_name"=>"Monica", "last_name"=>"Driscoll", "scopus_author_id"=>"7101716103"}, {"first_name"=>"Cynthia", "last_name"=>"Kenyon", "scopus_author_id"=>"20634969200"}], "year"=>2008, "source"=>"PLoS Genetics", "identifiers"=>{"issn"=>"15537390", "scopus"=>"2-s2.0-40149105890", "pui"=>"351328534", "doi"=>"10.1371/journal.pgen.0040024", "isbn"=>"1553-7404 (Electronic)\\r1553-7390 (Linking)", "sgr"=>"40149105890", "pmid"=>"18282106"}, "id"=>"32ba071e-7d5b-3ea5-8d4b-dfc8612f7f7e", "abstract"=>"In many organisms, dietary restriction appears to extend lifespan, at least in part, by down-regulating the nutrient-sensor TOR (Target Of Rapamycin). TOR inhibition elicits autophagy, the large-scale recycling of cytoplasmic macromolecules and organelles. In this study, we asked whether autophagy might contribute to the lifespan extension induced by dietary restriction in C. elegans. We find that dietary restriction and TOR inhibition produce an autophagic phenotype and that inhibiting genes required for autophagy prevents dietary restriction and TOR inhibition from extending lifespan. The longevity response to dietary restriction in C. elegans requires the PHA-4 transcription factor. We find that the autophagic response to dietary restriction also requires PHA-4 activity, indicating that autophagy is a transcriptionally regulated response to food limitation. In spite of the rejuvenating effect that autophagy is predicted to have on cells, our findings suggest that autophagy is not sufficient to extend lifespan. Long-lived daf-2 insulin/IGF-1 receptor mutants require both autophagy and the transcription factor DAF-16/FOXO for their longevity, but we find that autophagy takes place in the absence of DAF-16. Perhaps autophagy is not sufficient for lifespan extension because although it provides raw material for new macromolecular synthesis, DAF-16/FOXO must program the cells to recycle this raw material into cell-protective longevity proteins.", "link"=>"http://www.mendeley.com/research/role-autophagy-extension-lifespan-dietary-restriction-c-elegans", "reader_count"=>415, "reader_count_by_academic_status"=>{"Unspecified"=>13, "Professor > Associate Professor"=>29, "Librarian"=>1, "Researcher"=>73, "Student > Doctoral Student"=>11, "Student > Ph. D. 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  • {"month"=>"11", "year"=>"2020", "pdf_views"=>"30", "xml_views"=>"0", "html_views"=>"34"}

Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/936698"], "description"=>"<div><p>LGG-1::GFP-positive puncta labeling autophagic membranes [<a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.0040024#pgen-0040024-b022\" target=\"_blank\">22</a>] were counted in wild-type or in food-limited animals.</p><p>(A) Micrographs of <i>eat-2(ad1116)</i> L3 larvae expressing GFP-tagged <i>lgg-1</i>/LC3. Arrow indicates autophagic focus. Magnification is indicated.</p><p>(B) Average number of LGG-1::GFP-containing puncta in <i>eat-2(ad1116)</i> mutants and N2 wild-type animals (WT), <i>p</i> < 0.0001.</p><p>(C) Average number of LGG-1::GFP-containing puncta in N2 wild-type, food-restricted animals grown in liquid media (WT, food limited) and N2 wild-type animals grown in liquid with a higher concentration of bacteria (WT, fully fed), <i>p</i> < 0.0001; see <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.0040024#s4\" target=\"_blank\">Methods</a>.</p><p>Between three and ten seam cells were counted in each of 20–40 animals using high-power microscopy and averaged. <i>n</i>, total number of seam cells observed. Error bars: ±SEM. <i>p</i>-Values were calculated as unpaired, two-tailed t-test. Animals were raised at 20 °C. Please see <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.0040024#pgen-0040024-st001\" target=\"_blank\">Table S1</a> for quantification of all data.</p></div>", "links"=>[], "tags"=>["Biochemistry", "developmental biology", "genetics and genomics", "molecular biology"], "article_id"=>607139, "categories"=>["Molecular Biology", "Biochemistry", "Genetics", "Developmental Biology"], "users"=>["Malene Hansen", "Abha Chandra", "Laura L Mitic", "Brian Onken", "Monica Driscoll", "Cynthia Kenyon"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.0040024.g001", "stats"=>{"downloads"=>1, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Dietary_Restriction_Increases_the_Level_of_Autophagy_/607139", "title"=>"Dietary Restriction Increases the Level of Autophagy", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2008-02-15 01:58:59"}
  • {"files"=>["https://ndownloader.figshare.com/files/461814", "https://ndownloader.figshare.com/files/461826", "https://ndownloader.figshare.com/files/461833", "https://ndownloader.figshare.com/files/461843", "https://ndownloader.figshare.com/files/461849", "https://ndownloader.figshare.com/files/461853", "https://ndownloader.figshare.com/files/461862", "https://ndownloader.figshare.com/files/461878", "https://ndownloader.figshare.com/files/461883", "https://ndownloader.figshare.com/files/461888", "https://ndownloader.figshare.com/files/461893"], "description"=>"<div><p>In many organisms, dietary restriction appears to extend lifespan, at least in part, by down-regulating the nutrient-sensor TOR (Target Of Rapamycin). TOR inhibition elicits autophagy, the large-scale recycling of cytoplasmic macromolecules and organelles. In this study, we asked whether autophagy might contribute to the lifespan extension induced by dietary restriction in C. elegans. We find that dietary restriction and TOR inhibition produce an autophagic phenotype and that inhibiting genes required for autophagy prevents dietary restriction and TOR inhibition from extending lifespan. The longevity response to dietary restriction in C. elegans requires the PHA-4 transcription factor. We find that the autophagic response to dietary restriction also requires PHA-4 activity, indicating that autophagy is a transcriptionally regulated response to food limitation. In spite of the rejuvenating effect that autophagy is predicted to have on cells, our findings suggest that autophagy is not sufficient to extend lifespan. Long-lived <em>daf-2</em> insulin/IGF-1 receptor mutants require both autophagy and the transcription factor DAF-16/FOXO for their longevity, but we find that autophagy takes place in the absence of DAF-16. Perhaps autophagy is not sufficient for lifespan extension because although it provides raw material for new macromolecular synthesis, DAF-16/FOXO must program the cells to recycle this raw material into cell-protective longevity proteins.</p></div>", "links"=>[], "tags"=>["autophagy", "lifespan", "dietary"], "article_id"=>151012, "categories"=>["Molecular Biology", "Biochemistry", "Genetics", "Developmental Biology"], "users"=>["Malene Hansen", "Abha Chandra", "Laura L Mitic", "Brian Onken", "Monica Driscoll", "Cynthia Kenyon"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.0040024.sg001", "https://dx.doi.org/10.1371/journal.pgen.0040024.sg002", "https://dx.doi.org/10.1371/journal.pgen.0040024.sg003", "https://dx.doi.org/10.1371/journal.pgen.0040024.sg004", "https://dx.doi.org/10.1371/journal.pgen.0040024.sg005", "https://dx.doi.org/10.1371/journal.pgen.0040024.sg006", "https://dx.doi.org/10.1371/journal.pgen.0040024.sg007", "https://dx.doi.org/10.1371/journal.pgen.0040024.st001", "https://dx.doi.org/10.1371/journal.pgen.0040024.st002", "https://dx.doi.org/10.1371/journal.pgen.0040024.st003", "https://dx.doi.org/10.1371/journal.pgen.0040024.st004"], "stats"=>{"downloads"=>54, "page_views"=>17, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/A_Role_for_Autophagy_in_the_Extension_of_Lifespan_by_Dietary_Restriction_in_C_elegans_/151012", "title"=>"A Role for Autophagy in the Extension of Lifespan by Dietary Restriction in C. elegans", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2008-02-15 00:16:52"}
  • {"files"=>["https://ndownloader.figshare.com/files/937080"], "description"=>"<div><p>(A) Average number of LGG-1::GFP-containing puncta in N2 wild-type animals (WT) fed either control bacteria or bacteria expressing <i>daf-2</i> (as a control) or <i>rab-10</i> dsRNA for two generations. <i>p</i> < 0.0001 for either <i>daf-2</i> or <i>rab-10</i> RNAi treatment compared to control RNAi treatment, unpaired, two-tailed t-test. <i>n</i>, total number of seam cells observed. Error bars: ±SEM. See <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.0040024#pgen-0040024-g001\" target=\"_blank\">Figure 1</a> for details. Please see <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.0040024#pgen-0040024-st001\" target=\"_blank\">Table S1</a> for quantification of all data.</p><p>(B) Average number of LGG-1::GFP-containing puncta in <i>rab-10(ok1494)</i> mutants compared to N2 wild-type animals (WT), <i>p</i> < 0.0001, unpaired, two-tailed t-test. <i>n</i>, total number of seam cells observed. Error bars: ±SEM. Please see <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.0040024#pgen-0040024-g001\" target=\"_blank\">Figure 1</a> for details. Please see <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.0040024#pgen-0040024-st001\" target=\"_blank\">Table S1</a> for quantification of all data.</p><p>(C) Survival curves of <i>rab-10(ok1494)</i> animals fed either control bacteria or bacteria expressing <i>bec-1</i> or <i>vps-34</i> dsRNA during adulthood at 20 °C. Mean lifespan was 27.9 d for control, 19.9 d for <i>bec-1</i> RNAi, and 22.1 d for <i>vps-34</i> RNAi<i>,</i> all pair-wise comparisons to control, <i>p</i> < 0.0001, Log-rank (Mantel-Cox) test. This experiment was performed two times. Please see <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.0040024#pgen-0040024-t003\" target=\"_blank\">Table 3</a> for additional data.</p><p>(D) Survival curves of N2 wild-type animals (WT) fed either control bacteria or bacteria expressing <i>bec-1</i> or <i>vps-34</i> dsRNA during adulthood at 20 °C. These assays were performed at the same time as the <i>rab-10</i> lifespan analysis shown in <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.0040024#pgen-0040024-g005\" target=\"_blank\">Figure 5</a>C. Mean lifespan was 22.9 d for control, 23.6 d for <i>bec-1</i> RNAi, and 24.5 d for <i>vps-34</i> RNAi, pair-wise comparison to control, <i>p</i> = 0.057 and <i>p</i> = 0.16, respectively, Log-rank (Mantel-Cox) test. Please see <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.0040024#pgen-0040024-t001\" target=\"_blank\">Table 1</a> for additional data.</p></div>", "links"=>[], "tags"=>["gtpase"], "article_id"=>607529, "categories"=>["Molecular Biology", "Biochemistry", "Genetics", "Developmental Biology"], "users"=>["Malene Hansen", "Abha Chandra", "Laura L Mitic", "Brian Onken", "Monica Driscoll", "Cynthia Kenyon"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.0040024.g005", "stats"=>{"downloads"=>3, "page_views"=>36, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Inhibition_of_the_Small_GTPase_rab_10_Increases_Autophagy_/607529", "title"=>"Inhibition of the Small GTPase <i>rab-10</i> Increases Autophagy", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2008-02-15 02:05:29"}
  • {"files"=>["https://ndownloader.figshare.com/files/936865"], "description"=>"<div><p>(A) Average number of LGG-1::GFP-containing puncta in <i>eat-2(ad1116)</i> progeny of animals fed either control bacteria or bacteria expressing <i>bec-1</i>, <i>vps-34</i> or <i>pha-4</i> dsRNA their entire lives. <i>p</i> ≤ 0.0001 for <i>bec-1, vps-34</i> and <i>pha-4</i> RNAi treatments compared to control, respectively, unpaired, two-tailed t-test. <i>n</i>, total number of seam cells observed. Error bars: ±SEM. See <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.0040024#pgen-0040024-g001\" target=\"_blank\">Figure 1</a> for details.</p><p>(B) Average number of LGG-1::GFP-containing puncta in <i>rab-10(ok1494)</i> progeny of animals fed either control bacteria or bacteria expressing <i>pha-4</i> dsRNA their entire lives; <i>p</i> < 0.0001, unpaired, two-tailed t-test. <i>n</i>, total number of seam cells observed. Error bars: ±SEM. Please see <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.0040024#pgen-0040024-g001\" target=\"_blank\">Figure 1</a> for details and <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.0040024#pgen-0040024-st001\" target=\"_blank\">Table S1</a> for quantification of data. Feeding mutants for several generations with <i>pha-4</i> dsRNA, inhibited development and sharply decreased the number of eggs laid ([<a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.0040024#pgen-0040024-b046\" target=\"_blank\">46</a>], data not shown). However, the loss of many embryos was unlikely to bias our findings, since many progeny of <i>daf-2</i> mutants treated with <i>pha-4</i> RNAi also died but those that did not exhibited a robust autophagy phenotype (<a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.0040024#pgen-0040024-g006\" target=\"_blank\">Figure 6</a>).</p></div>", "links"=>[], "tags"=>["foxa", "transcription", "decreases", "autophagy"], "article_id"=>607308, "categories"=>["Molecular Biology", "Biochemistry", "Genetics", "Developmental Biology"], "users"=>["Malene Hansen", "Abha Chandra", "Laura L Mitic", "Brian Onken", "Monica Driscoll", "Cynthia Kenyon"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.0040024.g003", "stats"=>{"downloads"=>3, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Inhibition_of_the_FOXA_Transcription_Factor_pha_4_Decreases_Autophagy_in_eat_2_and_rab_10_Mutants_/607308", "title"=>"Inhibition of the FOXA Transcription Factor <i>pha-4</i> Decreases Autophagy in <i>eat-2</i> and <i>rab-10</i> Mutants", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2008-02-15 02:01:48"}
  • {"files"=>["https://ndownloader.figshare.com/files/937263"], "description"=>"<p>In response to dietary restriction using the <i>eat-2</i> mutation, TOR and RAB-10 activities fall, which triggers autophagy. Autophagy requires altered gene expression, since its appearance requires the transcription factor PHA-4. Autophagy is necessary but not sufficient for lifespan extension in long-lived <i>daf-2</i> insulin/IGF-1-receptor mutants; instead, autophagy and the DAF-16/FOXO transcription factor are both required, independently, for lifespan extension. Inhibiting protein synthesis in well-fed animals may activate a distinct longevity pathway, since inhibiting protein synthesis in the context of dietary restriction produces a lifespan extension that requires autophagy gene function, whereas inhibiting protein synthesis in well-fed animals produces a lifespan extension that is independent of autophagy gene function. The <i>sir-2</i> histone deacetylase is not in this diagram, as we [<a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.0040024#pgen-0040024-b006\" target=\"_blank\">6</a>] and several other groups [<a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.0040024#pgen-0040024-b066\" target=\"_blank\">66</a>–<a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.0040024#pgen-0040024-b068\" target=\"_blank\">68</a>] have found that <i>sir-2</i> deletion mutations do not prevent dietary restriction from increasing lifespan in <i>C. elegans.</i></p>", "links"=>[], "tags"=>["autophagy", "lifespan", "dietary"], "article_id"=>607709, "categories"=>["Molecular Biology", "Biochemistry", "Genetics", "Developmental Biology"], "users"=>["Malene Hansen", "Abha Chandra", "Laura L Mitic", "Brian Onken", "Monica Driscoll", "Cynthia Kenyon"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.0040024.g007", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Model_for_the_Role_of_Autophagy_in_Lifespan_Extension_by_Dietary_Restriction_in_C_elegans_/607709", "title"=>"Model for the Role of Autophagy in Lifespan Extension by Dietary Restriction in C. elegans", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2008-02-15 02:08:29"}
  • {"files"=>["https://ndownloader.figshare.com/files/936984"], "description"=>"<div><p>(A) Average number of LGG-1::GFP-containing puncta in <i>let-363</i>/TOR RNAi-arrested animals compared to N2 wild-type animals (WT) grown on control (vector-only) bacteria, <i>p</i> < 0.0001, unpaired, two-tailed t-test. <i>n</i>, total number of seam cells observed. Error bars: ±SEM. See <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.0040024#pgen-0040024-g001\" target=\"_blank\">Figure 1</a> for details. We were not able to detect increased LGG-1::GFP puncta in long-lived <i>let-363(RNAi)</i> adults; however, one generation of <i>daf-2</i> RNAi, our positive control, did not significantly increase the number of foci in adults either (data not shown). Please see <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.0040024#pgen-0040024-st001\" target=\"_blank\">Table S1</a> for quantification of all data.</p><p>(B) Average number of LGG-1::GFP-containing puncta in <i>daf-15(m81)/unc-24(e138)</i> heterozygotes (<i>daf-15/+)</i> compared to N2 wild-type animals (WT), <i>p</i> < 0.0001, unpaired, two-tailed t-test. <i>n</i>, total number of seam cells observed. Error bars: ±SEM. See <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.0040024#pgen-0040024-g001\" target=\"_blank\">Figure 1</a> for details. Please see <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.0040024#pgen-0040024-st001\" target=\"_blank\">Table S1</a> for quantification of all data. <i>daf-15</i> encodes the TOR-binding partner Raptor.</p><p>(C) Survival curves of <i>daf-15(m81)/unc-24(e138)</i> heterozygotes (<i>daf-15/+,</i> strain DR412) fed either control bacteria or bacteria expressing <i>bec-1</i> dsRNA during adulthood at 20 °C. Mean lifespan: <i>daf-15/+</i> animals grown on control RNAi-bacteria: 25.1 d, <i>daf-15/+</i>animals on <i>bec-1</i> RNAi: 20.8 d, <i>p</i> = 0.0008, Log-rank (Mantel-Cox) test. The lifespan of <i>daf-15/+</i> animals grown on <i>bec-1</i> RNAi-bacteria during adulthood was measured again, yielding similar results; the lifespan of <i>daf-15/+</i> animals was also measured three times following whole-life RNAi exposure. In these experiments, <i>bec-1</i> RNAi generally shortened the mean lifespan of <i>daf-15/+</i> animals to a greater extent than it shortened the lifespan of wild type. (We also attempted to perform double-RNAi experiments, in which animals were cultured on a 50:50 mixture of <i>let-363/</i>TOR and <i>bec-1</i> [or control] RNAi bacteria. Although the trends we saw were in the expected direction, the effects produced by half-strength RNAi were small and not statistically significant [data not shown].) Please see <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.0040024#pgen-0040024-t002\" target=\"_blank\">Table 2</a> for additional data.</p><p>(D) Survival curves of wild-type animals derived from strain DR412 (WT) fed either control bacteria or bacteria expressing <i>bec-1</i> dsRNA throughout their whole life at 20 °C. These assays were performed concurrently with the <i>daf-15/+</i> lifespan analysis shown in <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.0040024#pgen-0040024-g004\" target=\"_blank\">Figure 4</a>C. WT grown on control RNAi-bacteria: 21.4 d, WT on <i>bec-1</i> RNAi-bacteria: 21.1 d (<i>p</i> = 0.34), <i>p</i> between <i>daf-15/+</i> and WT grown on control RNAi-bacteria, <i>p</i> < 0.0001, Log-rank (Mantel-Cox) test. Please see <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.0040024#pgen-0040024-t002\" target=\"_blank\">Table 2</a> for additional data.</p></div>", "links"=>[], "tags"=>["tor-pathway", "autophagy", "autophagy-associated", "adulthood"], "article_id"=>607427, "categories"=>["Molecular Biology", "Biochemistry", "Genetics", "Developmental Biology"], "users"=>["Malene Hansen", "Abha Chandra", "Laura L Mitic", "Brian Onken", "Monica Driscoll", "Cynthia Kenyon"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.0040024.g004", "stats"=>{"downloads"=>2, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Animals_with_Low_TOR_Pathway_Activity_Exhibit_Increased_Autophagy_and_Require_the_Autophagy_associated_Gene_bec_1_during_Adulthood_to_Live_Long_/607427", "title"=>"Animals with Low TOR-Pathway Activity Exhibit Increased Autophagy and Require the Autophagy-associated Gene <i>bec-1</i> during Adulthood to Live Long", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2008-02-15 02:03:47"}
  • {"files"=>["https://ndownloader.figshare.com/files/937168"], "description"=>"<div><p>(A) Average number of LGG-1::GFP-containing puncta in <i>daf-2(e1370)</i> progeny of animals fed either control bacteria or bacteria expressing <i>bec-1</i>, <i>vps-34</i>, or <i>pha-4</i> dsRNA for their entire lives. <i>p</i> < 0.0001 for <i>bec-1</i> and <i>vps-34</i> RNAi-bacteria compared to control RNAi-bacteria, respectively, <i>p</i> = 0.17 for <i>pha-4</i> RNAi-bacteria compared to control RNAi-bacteria, unpaired, two-tailed t-test. <i>n</i>, total number of seam cells observed. Error bars: ±SEM. See <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.0040024#pgen-0040024-g001\" target=\"_blank\">Figure 1</a> for details. Feeding <i>daf-2</i> mutants for several generations with <i>pha-4</i> dsRNA sharply decreased the number of eggs laid (data not shown). The mean lifespan of <i>daf-2(e1370)</i> animals was shortened 12.5% by <i>pha-4</i> RNAi ([<a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.0040024#pgen-0040024-b028\" target=\"_blank\">28</a>] and data not shown), and we measured an 11% decrease in puncta in <i>daf-2(e1370)</i> animals fed <i>pha-4</i> RNAi. Even though this decrease was not statistically significant it remains possible that it relates to the small difference seen in lifespan.</p><p>(B) Average number of LGG-1::GFP-containing puncta in <i>daf-16(mu86); daf-2(e1370)</i> double mutants compared to <i>daf-2(e1370)</i> animals; <i>p =</i> 0.50, unpaired, two-tailed t-test. N2 wild-type animals (WT) are shown for comparison. <i>n</i>, total number of seam cells observed. Error bars: ±SEM. See <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.0040024#pgen-0040024-g001\" target=\"_blank\">Figure 1</a> for details. The double mutant expressing the LGG-1 reporter had a mean lifespan similar to non-transgenic <i>daf-16</i>; <i>daf-2</i> double mutants (data not shown, [<a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.0040024#pgen-0040024-b065\" target=\"_blank\">65</a>]). Please see <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.0040024#pgen-0040024-st001\" target=\"_blank\">Table S1</a> for quantification of all data.</p></div>", "links"=>[], "tags"=>["autophagy", "receptor", "mutants", "transcription"], "article_id"=>607607, "categories"=>["Molecular Biology", "Biochemistry", "Genetics", "Developmental Biology"], "users"=>["Malene Hansen", "Abha Chandra", "Laura L Mitic", "Brian Onken", "Monica Driscoll", "Cynthia Kenyon"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.0040024.g006", "stats"=>{"downloads"=>1, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Increased_Autophagy_in_daf_2_insulin_IGF_Receptor_Mutants_Is_Independent_of_the_daf_16_FOXO_and_pha_4_FOXA_Transcription_Factors_/607607", "title"=>"Increased Autophagy in <i>daf-2/</i>insulin/IGF Receptor Mutants Is Independent of the <i>daf-16</i>/FOXO and <i>pha-4</i>/FOXA Transcription Factors", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2008-02-15 02:06:47"}
  • {"files"=>["https://ndownloader.figshare.com/files/936784"], "description"=>"<div><p>(A) Survival curves of <i>eat-2(ad1116)</i> animals fed either control bacteria or bacteria expressing <i>bec-1</i> dsRNA during adulthood at 20 °C. Mean lifespan was 23.7 d for control and 19.6 d for <i>bec-1</i> RNAi<i>, p</i> < 0.0001, Log-rank (Mantel-Cox) test. This experiment was performed a total of six times, and <i>bec-1</i> RNAi shortened the lifespan of <i>eat-2</i> animals ∼15%–30%. Please see <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.0040024#pgen-0040024-t001\" target=\"_blank\">Table 1</a> for additional data.</p><p>(B) Survival curves of N2 wild-type animals (WT) fed either control bacteria or bacteria expressing <i>bec-1</i> dsRNA during adulthood at 20 °C. These assays were performed concurrently with the <i>eat-2</i> mutant lifespan analysis in <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.0040024#pgen-0040024-g002\" target=\"_blank\">Figure 2</a>A. Mean lifespan was 17.3 d for control and 18.9 d for <i>bec-1</i> RNAi. <i>p</i> = 0.045, Log-rank (Mantel-Cox) test. Depletion of <i>bec-1</i> did not significantly change the lifespan of N2 or sterile <i>fer-15(b26); fem-1(hc17)</i> animals in any of six experiments. Please see <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.0040024#pgen-0040024-t001\" target=\"_blank\">Table 1</a> for additional data.</p><p>(C) Survival curves of <i>eat-2(ad1116)</i> animals fed either control bacteria or bacteria expressing <i>vps-34</i> dsRNA during adulthood at 20 °C. Mean lifespan was 27.6 d for control and 22.8 d for <i>vps-34</i> RNAi<i>, p</i> = 0.0003, Log-rank (Mantel-Cox) test. This experiment was performed a total of four times. Please see <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.0040024#pgen-0040024-t001\" target=\"_blank\">Table 1</a> for additional data.</p><p>(D) Survival curves of sterile <i>fer-15(b26); fem-1(hc17)</i> animals (WT) fed either control bacteria or bacteria expressing <i>vps-34</i> dsRNA during adulthood at 20 °C. These assays were performed at the same time as the <i>eat-2</i> lifespan analysis shown in <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.0040024#pgen-0040024-g002\" target=\"_blank\">Figure 2</a>C. Mean lifespan was 21.5 d for control and 23.3 d for <i>bec-1</i> RNAi. <i>p</i> = 0.14, Log-rank (Mantel-Cox) test. Depletion of <i>vps-34</i> did not significantly change the lifespan of N2 or sterile <i>fer-15(b26); fem-1(hc17)</i> animals in each of six different experiments. Please see <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.0040024#pgen-0040024-t001\" target=\"_blank\">Table 1</a> for additional data.</p></div>", "links"=>[], "tags"=>["genes", "autophagy", "shortens", "lifespan"], "article_id"=>607229, "categories"=>["Molecular Biology", "Biochemistry", "Genetics", "Developmental Biology"], "users"=>["Malene Hansen", "Abha Chandra", "Laura L Mitic", "Brian Onken", "Monica Driscoll", "Cynthia Kenyon"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.0040024.g002", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Inhibition_of_Genes_Required_for_Autophagy_Shortens_the_Long_Lifespan_of_eat_2_Mutants_/607229", "title"=>"Inhibition of Genes Required for Autophagy Shortens the Long Lifespan of <i>eat-2</i> Mutants", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2008-02-15 02:00:29"}

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Relative Metric

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