Fragile DNA Repair Mechanism Reduces Ageing in Multicellular Model
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{"title"=>"Fragile DNA repair mechanism reduces ageing in multicellular model", "type"=>"journal", "authors"=>[{"first_name"=>"Kristian Moss", "last_name"=>"Bendtsen", "scopus_author_id"=>"22949748000"}, {"first_name"=>"Jeppe", "last_name"=>"Juul", "scopus_author_id"=>"54412307800"}, {"first_name"=>"Ala", "last_name"=>"Trusina", "scopus_author_id"=>"6602555462"}], "year"=>2012, "source"=>"PLoS ONE", "identifiers"=>{"scopus"=>"2-s2.0-84860489736", "doi"=>"10.1371/journal.pone.0036018", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "issn"=>"19326203", "pmid"=>"22567122", "pui"=>"364721467", "sgr"=>"84860489736"}, "id"=>"0c3d7c0a-fd69-3844-b921-aee774e943c4", "abstract"=>"DNA damages, as well as mutations, increase with age. It is believed that these result from increased genotoxic stress and decreased capacity for DNA repair. The two causes are not independent, DNA damage can, for example, through mutations, compromise the capacity for DNA repair, which in turn increases the amount of unrepaired DNA damage. Despite this vicious circle, we ask, can cells maintain a high DNA repair capacity for some time or is repair capacity bound to continuously decline with age? We here present a simple mathematical model for ageing in multicellular systems where cells subjected to DNA damage can undergo full repair, go apoptotic, or accumulate mutations thus reducing DNA repair capacity. Our model predicts that at the tissue level repair rate does not continuously decline with age, but instead has a characteristic extended period of high and non-declining DNA repair capacity, followed by a rapid decline. Furthermore, the time of high functionality increases, and consequently slows down the ageing process, if the DNA repair mechanism itself is vulnerable to DNA damages. Although counterintuitive at first glance, a fragile repair mechanism allows for a faster removal of compromised cells, thus freeing the space for healthy peers. This finding might be a first step toward understanding why a mutation in single DNA repair protein (e.g. Wrn or Blm) is not buffered by other repair proteins and therefore, leads to severe ageing disorders.", "link"=>"http://www.mendeley.com/research/fragile-dna-repair-mechanism-reduces-ageing-multicellular-model", "reader_count"=>18, "reader_count_by_academic_status"=>{"Researcher"=>7, "Student > Ph. D. Student"=>8, "Student > Master"=>1, "Other"=>1, "Student > Bachelor"=>1}, "reader_count_by_user_role"=>{"Researcher"=>7, "Student > Ph. D. Student"=>8, "Student > Master"=>1, "Other"=>1, "Student > Bachelor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>4, "Agricultural and Biological Sciences"=>7, "Medicine and Dentistry"=>1, "Physics and Astronomy"=>4, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Physics and Astronomy"=>{"Physics and Astronomy"=>4}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>7}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>4}, "Unspecified"=>{"Unspecified"=>1}}, "reader_count_by_country"=>{"Mexico"=>1, "United Kingdom"=>1}, "group_count"=>0}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/643696"], "description"=>"<p>Since cells with a low rate of repair are more likely to go apoptotic, a temporary steady state exists where the repair rate of the system fluctuates around an average value of The length of time, before the system leaves this temporary state increases drastically with the size <i>N</i> of the system. If is large, a high rate of repair may be maintained without renewal from the stem cell pool, and consequently the organism ages more slowly. The simulation is carried out with parameters The median of 20 simulation runs is showed.</p>", "links"=>[], "tags"=>["drops", "cells", "irreversibly", "accumulate"], "article_id"=>314189, "categories"=>["Biological Sciences", "Physics", "Biochemistry", "Biophysics", "Mathematics", "Molecular Biology", "Genetics"], "users"=>["Kristian Moss Bendtsen", "Jeppe Juul", "Ala Trusina"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0036018.g002", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_average_repair_rate_of_the_system_drops_as_cells_irreversibly_accumulate_mutations_/314189", "title"=>"The average repair rate of the system drops as cells irreversibly accumulate mutations.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 05:38:44"}
  • {"files"=>["https://ndownloader.figshare.com/files/643571"], "description"=>"<p>When a cell acquires DNA damage, it may respond in one of three ways: i) Complete repair of the damage with probability <i>R</i>, ii) Apoptosis with probability <b> in which case another cell divides to keep the number of cells constant, iii) Accumulation of the damage through a mutation, reducing the rate of repair to</b></p>", "links"=>[], "tags"=>["acquires", "dna", "probability", "apoptosis", "divides", "cells", "accumulation", "reducing"], "article_id"=>314051, "categories"=>["Biological Sciences", "Physics", "Biochemistry", "Biophysics", "Mathematics", "Molecular Biology", "Genetics"], "users"=>["Kristian Moss Bendtsen", "Jeppe Juul", "Ala Trusina"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0036018.g001", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_When_a_cell_acquires_DNA_damage_it_may_respond_in_one_of_three_ways_i_Complete_repair_of_the_damage_with_probability_R_ii_Apoptosis_with_probability_in_which_case_another_cell_divides_to_keep_the_number_of_cells_constant_iii_Accumulation_of_the_damage_th/314051", "title"=>"When a cell acquires DNA damage, it may respond in one of three ways: i) Complete repair of the damage with probability <i>R</i>, ii) Apoptosis with probability <b> in which case another cell divides to keep the number of cells constant, iii) Accumulation of the damage through a mutation, reducing the rate of repair to</b>", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 05:37:57"}
  • {"files"=>["https://ndownloader.figshare.com/files/644068"], "description"=>"<p>The theoretically predicted distributions of repair rates in the well mixed systems, given by (5), is seen to agree well with the actual distribution during the temporary steady state. <b>b)</b> The distribution of repair rates as a function of time. (All parameters are set to the values given in the caption of <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0036018#pone-0036018-g002\" target=\"_blank\">figure 2</a>.)</p>", "links"=>[], "tags"=>["genetics and genomics", "molecular biology", "Computational biology", "biophysics", "physics", "Biochemistry", "mathematics"], "article_id"=>314557, "categories"=>["Biological Sciences", "Physics", "Biochemistry", "Biophysics", "Mathematics", "Molecular Biology", "Genetics"], "users"=>["Kristian Moss Bendtsen", "Jeppe Juul", "Ala Trusina"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0036018.g004", "stats"=>{"downloads"=>3, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_a_/314557", "title"=>"Fragile DNA Repair Mechanism Reduces Ageing in Multicellular Model - a)", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 05:40:44"}
  • {"files"=>["https://ndownloader.figshare.com/files/643866"], "description"=>"<p>a) The time spent in steady state increases with the initial repair rate , rate of apoptosis <i>a</i>, and fragility of the repair mechanism Δ. (Parameters that are not varied are set to the values given in the caption of <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0036018#pone-0036018-g002\" target=\"_blank\">figure 2</a>) b) For the well mixed system, the time spent at steady state, increases drastically with system size <i>N</i>. For spatially structured systems the increase is linear. (Parameters used: ), </p>", "links"=>[], "tags"=>["spent", "increases", "apoptosis", "fragility", "varied", "caption", "drastically", "spatially", "structured", "systems"], "article_id"=>314349, "categories"=>["Biological Sciences", "Physics", "Biochemistry", "Biophysics", "Mathematics", "Molecular Biology", "Genetics"], "users"=>["Kristian Moss Bendtsen", "Jeppe Juul", "Ala Trusina"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0036018.g003", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_a_The_time_spent_in_steady_state_increases_with_the_initial_repair_rate_rate_of_apoptosis_a_and_fragility_of_the_repair_mechanism_Parameters_that_are_not_varied_are_set_to_the_values_given_in_the_caption_of_figure_2_b_For_the_well_mixed_system_the_time_s/314349", "title"=>"a) The time spent in steady state increases with the initial repair rate , rate of apoptosis <i>a</i>, and fragility of the repair mechanism Δ. (Parameters that are not varied are set to the values given in the caption of figure 2) b) For the well mixed system, the time spent at steady state, increases drastically with system size <i>N</i>. For spatially structured systems the increase is linear. (Parameters used: ),", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 05:39:35"}

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