A Decline in p38 MAPK Signaling Underlies Immunosenescence in Caenorhabditis elegans
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{"title"=>"A decline in p38 MAPK signaling underlies immunosenescence in caenorhabditis elegans", "type"=>"journal", "authors"=>[{"first_name"=>"Matthew J.", "last_name"=>"Youngman", "scopus_author_id"=>"7003523548"}, {"first_name"=>"Zoë N.", "last_name"=>"Rogers", "scopus_author_id"=>"42862341700"}, {"first_name"=>"Dennis H.", "last_name"=>"Kim", "scopus_author_id"=>"55944791000"}], "year"=>2011, "source"=>"PLoS Genetics", "identifiers"=>{"issn"=>"15537390", "pui"=>"361887800", "sgr"=>"79957992660", "pmid"=>"21625567", "doi"=>"10.1371/journal.pgen.1002082", "isbn"=>"1553-7404 (Electronic) 1553-7390 (Linking)", "scopus"=>"2-s2.0-79957992660"}, "id"=>"04f377c1-ae09-37ab-95c8-163f57e406e1", "abstract"=>"The decline in immune function with aging, known as immunosenescence, has been implicated in evolutionarily diverse species, but the underlying molecular mechanisms are not understood. During aging in Caenorhabditis elegans, intestinal tissue deterioration and the increased intestinal proliferation of bacteria are observed, but how innate immunity changes during C. elegans aging has not been defined. Here we show that C. elegans exhibits increased susceptibility to bacterial infection with age, and we establish that aging is associated with a decline in the activity of the conserved PMK-1 p38 mitogen-activated protein kinase pathway, which regulates innate immunity in C. elegans. Our data define the phenomenon of innate immunosenescence in C. elegans in terms of the age-dependent dynamics of the PMK-1 innate immune signaling pathway, and they suggest that a cycle of intestinal tissue aging, immunosenescence, and bacterial proliferation leads to death in aging C. elegans.", "link"=>"http://www.mendeley.com/research/decline-p38-mapk-signaling-underlies-immunosenescence-caenorhabditis-elegans", "reader_count"=>63, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>5, "Researcher"=>20, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>21, "Student > Master"=>6, "Other"=>1, "Student > Bachelor"=>4, "Professor"=>4}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>5, "Researcher"=>20, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>21, "Student > Master"=>6, "Other"=>1, "Student > Bachelor"=>4, "Professor"=>4}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>2, "Agricultural and Biological Sciences"=>56, "Medicine and Dentistry"=>1, "Immunology and Microbiology"=>3, "Engineering"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>3}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>56}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}}, "reader_count_by_country"=>{"Hungary"=>1, "United States"=>2, "Brazil"=>1, "United Kingdom"=>1, "India"=>1}, "group_count"=>2}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/388108", "https://ndownloader.figshare.com/files/388137", "https://ndownloader.figshare.com/files/388159", "https://ndownloader.figshare.com/files/388201", "https://ndownloader.figshare.com/files/388235", "https://ndownloader.figshare.com/files/388255"], "description"=>"<div><p>The decline in immune function with aging, known as immunosenescence, has been implicated in evolutionarily diverse species, but the underlying molecular mechanisms are not understood. During aging in <em>Caenorhabditis elegans</em>, intestinal tissue deterioration and the increased intestinal proliferation of bacteria are observed, but how innate immunity changes during <em>C. elegans</em> aging has not been defined. Here we show that <em>C. elegans</em> exhibits increased susceptibility to bacterial infection with age, and we establish that aging is associated with a decline in the activity of the conserved PMK-1 p38 mitogen-activated protein kinase pathway, which regulates innate immunity in <em>C. elegans</em>. Our data define the phenomenon of innate immunosenescence in <em>C. elegans</em> in terms of the age-dependent dynamics of the PMK-1 innate immune signaling pathway, and they suggest that a cycle of intestinal tissue aging, immunosenescence, and bacterial proliferation leads to death in aging <em>C. elegans</em>.</p> </div>", "links"=>[], "tags"=>["p38", "mapk", "signaling", "underlies", "immunosenescence"], "article_id"=>136640, "categories"=>["Molecular Biology", "Genetics", "Microbiology", "Immunology"], "users"=>["Matthew J. Youngman", "Zoë N. Rogers", "Dennis H. Kim"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1002082.s001", "https://dx.doi.org/10.1371/journal.pgen.1002082.s002", "https://dx.doi.org/10.1371/journal.pgen.1002082.s003", "https://dx.doi.org/10.1371/journal.pgen.1002082.s004", "https://dx.doi.org/10.1371/journal.pgen.1002082.s005", "https://dx.doi.org/10.1371/journal.pgen.1002082.s006"], "stats"=>{"downloads"=>5, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/A_Decline_in_p38_MAPK_Signaling_Underlies_Immunosenescence_in_Caenorhabditis_elegans_/136640", "title"=>"A Decline in p38 MAPK Signaling Underlies Immunosenescence in <em>Caenorhabditis elegans</em>", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2011-05-19 01:50:40"}
  • {"files"=>["https://ndownloader.figshare.com/files/773396"], "description"=>"<p>(A) Fraction of wild type N2 <i>C. elegans</i> (white bars) or <i>pmk-1(km25)</i> mutants (grey bars) maintained on lawns of <i>E. coli</i> OP50 that exhibit intestinal distention at Days 6, 9, and 12 of adulthood. Inset, ratio of the average number of <i>pmk-1</i> mutants with intestinal distention versus the average number of wild type animals with intestinal distention at Days 6, 9, or 12 of adulthood. (B) As the primary immune cells in <i>C. elegans</i>, age-related damage to intestinal cells may impair their ability to execute processes required for immune protection, such as the expression of immune effector proteins, including those regulated by the PMK-1 pathway. The consequent reduction in host defense would lead to increased colonization of the <i>C. elegans</i> intestine by pathogenic microbes, which contribute to and amplify intestinal cell deterioration during the infection process. Thus a self-perpetuating cycle of increased intestinal deterioration, decreased immunity, and increased accumulation of bacteria may underlie immunosenescence and significantly contribute to mortality later in life.</p>", "links"=>[], "tags"=>["intestinal", "proliferation"], "article_id"=>443770, "categories"=>["Molecular Biology", "Genetics", "Microbiology", "Immunology"], "users"=>["Matthew J. Youngman", "Zoë N. Rogers", "Dennis H. Kim"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002082.g006", "stats"=>{"downloads"=>1, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_A_cycle_of_intestinal_tissue_aging_immunosenescence_and_progressive_intestinal_proliferation_of_bacteria_towards_the_end_of_life_in_C_elegans_/443770", "title"=>"A cycle of intestinal tissue aging, immunosenescence, and progressive intestinal proliferation of bacteria towards the end of life in <i>C. elegans</i>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-05-19 01:02:50"}
  • {"files"=>["https://ndownloader.figshare.com/files/773488"], "description"=>"<p>The number of intestine-expressed genes (based on a list compiled from previous studies <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002082#pgen.1002082-McGhee1\" target=\"_blank\">[24]</a>, <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002082#pgen.1002082-Pauli1\" target=\"_blank\">[25]</a>) and PMK-1 transcriptional targets (identified previously <a href=\"http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1002082#pgen.1002082-Troemel1\" target=\"_blank\">[13]</a>) with levels of expression reduced by either ≥2-fold or ≥10-fold in Day 15 animals compared to expression levels in Day 6 adults is reported. The statistical significance of the fold difference among genes downregulated by 10-fold or more between Day 6 and Day 15 of adulthood is represented by a hypergeometric <i>p</i>-value.</p>", "links"=>[], "tags"=>["intestine-enriched", "genes", "pmk-1", "transcriptional", "targets", "downregulated", "15"], "article_id"=>443848, "categories"=>["Molecular Biology", "Genetics", "Microbiology", "Immunology"], "users"=>["Matthew J. Youngman", "Zoë N. Rogers", "Dennis H. Kim"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002082.t001", "stats"=>{"downloads"=>4, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Distribution_of_intestine_enriched_genes_and_PMK_1_transcriptional_targets_among_genes_downregulated_at_Day_15_versus_Day_6_of_adulthood_/443848", "title"=>"Distribution of intestine-enriched genes and PMK-1 transcriptional targets among genes downregulated at Day 15 versus Day 6 of adulthood.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2011-05-19 01:04:08"}
  • {"files"=>["https://ndownloader.figshare.com/files/773316"], "description"=>"<p>(A) Survival of wild type strain N2 (orange) and the <i>pmk-1</i>(<i>km25)</i> mutant (blue) transferred from <i>E. coli</i> OP50 to <i>P. aeruginosa</i> PA14 at L4, and at Days 3, 6, and 9 of adulthood (B–D, respectively), plotted as fraction of worms alive versus time.</p>", "links"=>[], "tags"=>["pmk-1", "p38", "mapk", "signaling"], "article_id"=>443686, "categories"=>["Molecular Biology", "Genetics", "Microbiology", "Immunology"], "users"=>["Matthew J. Youngman", "Zoë N. Rogers", "Dennis H. Kim"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002082.g005", "stats"=>{"downloads"=>0, "page_views"=>15, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Age_dependent_decrease_in_the_contribution_of_PMK_1_p38_MAPK_signaling_to_C_elegans_immunity_/443686", "title"=>"Age-dependent decrease in the contribution of PMK-1 p38 MAPK signaling to <i>C. elegans</i> immunity.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-05-19 01:01:26"}
  • {"files"=>["https://ndownloader.figshare.com/files/773200"], "description"=>"<p>(A) Scatter plots comparing gene expression levels in the <i>C. elegans</i> wild type N2 strain at Day 15 versus Day 6 of adulthood. Each dot represents an individual gene; brown, all genes on the full-genome microarray; blue, genes previously shown to exhibit enriched expression levels in the <i>C. elegans</i> intestine; red, genes previously identified as being regulated by the PMK-1 pathway. Genes on the solid diagonal line are expressed at equivalent levels at both time points. Genes below the dashed diagonal line are downregulated by more than 10-fold between Day 6 and Day 15 of adulthood. (B) qRT-PCR of endogenous C17H12.8 and T24B8.5 mRNA levels during aging relative to expression at Day 3 of adulthood. The average of three experiments using independent biological replicates of total RNA for cDNA synthesis is shown. Bars indicate standard deviation. (C) Fluorescence microscopy of <i>C. elegans</i> carrying the <i>agIs219</i> transgene, a GFP reporter of PMK-1 activity, at the indicated ages. (D) qRT-PCR of <i>pmk-1</i> transcript levels during aging relative to expression at L4. The average of two experiments using independent biological replicates of total RNA for cDNA synthesis is shown.</p>", "links"=>[], "tags"=>["pmk-1", "transcriptional", "targets", "aging"], "article_id"=>443568, "categories"=>["Molecular Biology", "Genetics", "Microbiology", "Immunology"], "users"=>["Matthew J. Youngman", "Zoë N. Rogers", "Dennis H. Kim"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002082.g003", "stats"=>{"downloads"=>2, "page_views"=>35, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_A_decline_in_expression_of_PMK_1_transcriptional_targets_during_aging_in_the_C_elegans_intestine_/443568", "title"=>"A decline in expression of PMK-1 transcriptional targets during aging in the <i>C. elegans</i> intestine.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-05-19 00:59:28"}
  • {"files"=>["https://ndownloader.figshare.com/files/773265"], "description"=>"<p>Immunoblot analysis of total and activated PMK-1 during aging. Total protein isolated from L4 larval stage <i>pmk-1(km25)</i> (lane 1), L4 <i>sek-1(km4)</i> (lane 2) or L4 and adult wild type N2 strain (lanes 3-8) was separated by SDS-PAGE, and immunoblots were decorated with antibodies to either PMK-1 (Total PMK-1), phosphorylated PMK-1 (Active PMK-1) or β-tubulin (Tubulin).</p>", "links"=>[], "tags"=>["gradual", "levels", "activated", "pmk-1", "adulthood"], "article_id"=>443630, "categories"=>["Molecular Biology", "Genetics", "Microbiology", "Immunology"], "users"=>["Matthew J. Youngman", "Zoë N. Rogers", "Dennis H. Kim"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002082.g004", "stats"=>{"downloads"=>1, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_A_gradual_reduction_in_the_levels_of_total_and_activated_PMK_1_protein_throughout_adulthood_in_C_elegans_/443630", "title"=>"A gradual reduction in the levels of total and activated PMK-1 protein throughout adulthood in <i>C. elegans</i>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-05-19 01:00:30"}
  • {"files"=>["https://ndownloader.figshare.com/files/773076"], "description"=>"<p>(A) Survival of wild type strain N2 maintained on <i>E. coli</i> OP50 plotted as fraction of worms alive versus time. Arrows indicate ages of worms when <i>P. aeruginosa</i> infection was initiated, when reporter gene expression was examined, and/or when total RNA was harvested for microarray analysis. (B) Schematic of <i>P. aeruginosa</i> infection assay. At the indicated ages, subsets of worms from a synchronized population cultured on a lawn of <i>E. coli</i> OP50 were transferred to plates containing a lawn of <i>P. aeruginosa</i> PA14, and their survival was monitored twice daily thereafter.</p>", "links"=>[], "tags"=>["aging", "pathogenic"], "article_id"=>443449, "categories"=>["Molecular Biology", "Genetics", "Microbiology", "Immunology"], "users"=>["Matthew J. Youngman", "Zoë N. Rogers", "Dennis H. Kim"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002082.g001", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Systematic_analysis_of_the_survival_of_aging_C_elegans_upon_challenge_with_pathogenic_bacteria_/443449", "title"=>"Systematic analysis of the survival of aging <i>C. elegans</i> upon challenge with pathogenic bacteria.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-05-19 00:57:29"}
  • {"files"=>["https://ndownloader.figshare.com/files/773142"], "description"=>"<p>(A) Survival of wild type strain N2 transferred from <i>E. coli</i> OP50 to <i>P. aeruginosa</i> PA14 at L4 (orange), Day 3 (magenta), Day 6 (blue), or Day 9 (green) plotted as fraction of worms alive versus time. (B) Accumulation of <i>P. aeruginosa</i> within the intestinal lumen of <i>C. elegans</i> at ∼24 h post-infection. Wild type N2 strain late larval stage (L4) and adult worms were infected with a strain of <i>P. aeruginosa</i> that expresses GFP and then scored the next day according to the extent of bacterial colonization of the intestine. The pattern of <i>P. aeruginosa</i> infection in individual animals was classified as either “None” when no GFP-expressing <i>P. aeruginosa</i> could be detected in the intestine, “Partial” when <i>P. aeruginosa</i> colonization of the intestine was incomplete or was localized to a bolus, or “Full” when the intestinal lumen was completely packed with bacteria along its entire length.</p>", "links"=>[], "tags"=>["susceptibility", "lethal"], "article_id"=>443511, "categories"=>["Molecular Biology", "Genetics", "Microbiology", "Immunology"], "users"=>["Matthew J. Youngman", "Zoë N. Rogers", "Dennis H. Kim"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1002082.g002", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Increased_susceptibility_of_C_elegans_to_lethal_infection_with_aging_/443511", "title"=>"Increased susceptibility of <i>C. elegans</i> to lethal infection with aging.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-05-19 00:58:31"}

PMC Usage Stats | Further Information

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Relative Metric

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