{"id":"https://openalex.org/W2002180347","doi":"https://doi.org/10.1159/000131597","title":"Evidence of clonal attenuation, clonal succession, and clonal expansion in mass cultures of aging Werner\u2019s syndrome skin fibroblasts","display_name":"Evidence of clonal attenuation, clonal succession, and clonal expansion in mass cultures of aging Werner\u2019s syndrome skin fibroblasts","publication_year":2008,"publication_date":"2008-05-07","ids":{"openalex":"https://openalex.org/W2002180347","doi":"https://doi.org/10.1159/000131597","mag":"2002180347","pmid":"https://pubmed.ncbi.nlm.nih.gov/7273855"},"language":"en","primary_location":{"id":"doi:10.1159/000131597","doi":"https://doi.org/10.1159/000131597","is_oa":false,"landing_page_url":"https://doi.org/10.1159/000131597","pdf_url":null,"source":{"id":"https://openalex.org/S4210179014","display_name":"Cytogenetics and Cell Genetics","issn_l":"0301-0171","issn":["0301-0171","1421-9816"],"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":["norway-1"],"host_organization":"https://openalex.org/P4310317820","host_organization_name":"Karger Publishers","host_organization_lineage":["https://openalex.org/P4310317820"],"host_organization_lineage_names":["Karger Publishers"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Cytogenetics and Cell Genetics","raw_type":"journal-article"},"volume":null,"type":"article","indexed_in":["crossref","pubmed"],"open_access":{"is_oa":false,"oa_status":"closed","oa_url":null,"any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5109996664","display_name":"Darrell Salk","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"D. Salk","raw_affiliation_strings":["Department of Pediatrics, and","D\u00edvision of Genetic Pathology,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Pediatrics, and","institution_ids":[]},{"raw_affiliation_string":"D\u00edvision of Genetic Pathology,","institution_ids":[]}]},{"author_position":"middle","author":{"id":null,"display_name":"K. Au","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"K. Au","raw_affiliation_strings":["D\u00edvision of Genetic Pathology,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"D\u00edvision of Genetic Pathology,","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5060439423","display_name":"Holger Hoehn","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I201448701","display_name":"University of Washington","ror":"https://ror.org/00cvxb145","country_code":"US","type":"education","lineage":["https://openalex.org/I201448701"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"H. Hoehn","raw_affiliation_strings":["Center for Inherited Diseases, University of Washington School of Medicine, Seattle","D\u00edvision of Genetic Pathology,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Center for Inherited Diseases, University of Washington School of Medicine, Seattle","institution_ids":["https://openalex.org/I201448701"]},{"raw_affiliation_string":"D\u00edvision of Genetic Pathology,","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5006448185","display_name":"Marc R. Stenchever","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"M.R. Stenchever","raw_affiliation_strings":["D\u00edvision of Genetic Pathology,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"D\u00edvision of Genetic Pathology,","institution_ids":[]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5059153511","display_name":"George M. Martin","orcid":"https://orcid.org/0000-0002-7974-818X","observed_orcids":["https://orcid.org/0000-0002-7974-818X"]},"institutions":[{"id":"https://openalex.org/I201448701","display_name":"University of Washington","ror":"https://ror.org/00cvxb145","country_code":"US","type":"education","lineage":["https://openalex.org/I201448701"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"G.M. Martin","raw_affiliation_strings":["Center for Inherited Diseases, University of Washington School of Medicine, Seattle","D\u00edvision of Genetic Pathology,"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Center for Inherited Diseases, University of Washington School of Medicine, Seattle","institution_ids":["https://openalex.org/I201448701"]},{"raw_affiliation_string":"D\u00edvision of Genetic Pathology,","institution_ids":[]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":null,"apc_paid":null,"fwci":0.4523,"has_fulltext":false,"cited_by_count":65,"citation_normalized_percentile":{"value":0.68354295,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":89,"max":96},"biblio":{"volume":"30","issue":"2","first_page":"108","last_page":"117"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10937","display_name":"Telomeres, Telomerase, and Senescence","score":0.9814000129699707,"subfield":{"id":"https://openalex.org/subfields/2737","display_name":"Physiology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T10937","display_name":"Telomeres, Telomerase, and Senescence","score":0.9814000129699707,"subfield":{"id":"https://openalex.org/subfields/2737","display_name":"Physiology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10676","display_name":"Genetics, Aging, and Longevity in Model Organisms","score":0.012900000438094139,"subfield":{"id":"https://openalex.org/subfields/1302","display_name":"Aging"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T11841","display_name":"Nuclear Structure and Function","score":0.0012000000569969416,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/werner-syndrome","display_name":"Werner syndrome","score":0.9279999732971191},{"id":"https://openalex.org/keywords/dermal-fibroblasts","display_name":"dermal fibroblasts","score":0.9559999704360962},{"id":"https://openalex.org/keywords/clonal-expansion","display_name":"clonal expansion","score":0.7210000157356262},{"id":"https://openalex.org/keywords/structural-chromosome-rearrangements","display_name":"structural chromosome rearrangements","score":0.8450000286102295},{"id":"https://openalex.org/keywords/cellular-senescence","display_name":"cellular senescence","score":0.8579999804496765},{"id":"https://openalex.org/keywords/replicative-lifespan","display_name":"replicative lifespan","score":0.8180000185966492},{"id":"https://openalex.org/keywords/tissue-hyperplasia","display_name":"tissue hyperplasia","score":0.8370000123977661},{"id":"https://openalex.org/keywords/in-vitro-aging","display_name":"in vitro aging","score":0.6330000162124634},{"id":"https://openalex.org/keywords/cytogenetic-markers","display_name":"cytogenetic markers","score":0.4490000009536743}],"concepts":[{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.8777279853820801},{"id":"https://openalex.org/C202751555","wikidata":"https://www.wikidata.org/wiki/Q221681","display_name":"In vitro","level":2,"score":0.5980561375617981},{"id":"https://openalex.org/C2778465436","wikidata":"https://www.wikidata.org/wiki/Q213098","display_name":"Progeria","level":3,"score":0.5972021222114563},{"id":"https://openalex.org/C2780381497","wikidata":"https://www.wikidata.org/wiki/Q463418","display_name":"Fibroblast","level":3,"score":0.5369330048561096},{"id":"https://openalex.org/C207001950","wikidata":"https://www.wikidata.org/wiki/Q141124","display_name":"In vivo","level":2,"score":0.5200309753417969},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.5158876180648804},{"id":"https://openalex.org/C2778090637","wikidata":"https://www.wikidata.org/wiki/Q1154619","display_name":"Werner syndrome","level":5,"score":0.4867730140686035},{"id":"https://openalex.org/C522857546","wikidata":"https://www.wikidata.org/wiki/Q2070979","display_name":"Senescence","level":2,"score":0.46971434354782104},{"id":"https://openalex.org/C81089528","wikidata":"https://www.wikidata.org/wiki/Q5134986","display_name":"clone (Java method)","level":3,"score":0.4577521085739136},{"id":"https://openalex.org/C113968399","wikidata":"https://www.wikidata.org/wiki/Q7559241","display_name":"Somatic evolution in cancer","level":3,"score":0.438823938369751},{"id":"https://openalex.org/C30481170","wikidata":"https://www.wikidata.org/wiki/Q37748","display_name":"Chromosome","level":3,"score":0.4338294267654419},{"id":"https://openalex.org/C138626823","wikidata":"https://www.wikidata.org/wiki/Q916504","display_name":"Chromosomal translocation","level":3,"score":0.4309009313583374},{"id":"https://openalex.org/C53226629","wikidata":"https://www.wikidata.org/wiki/Q189967","display_name":"Karyotype","level":4,"score":0.41430723667144775},{"id":"https://openalex.org/C153911025","wikidata":"https://www.wikidata.org/wiki/Q7202","display_name":"Molecular biology","level":1,"score":0.37436866760253906},{"id":"https://openalex.org/C552990157","wikidata":"https://www.wikidata.org/wiki/Q7430","display_name":"DNA","level":2,"score":0.13751807808876038},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.10547783970832825},{"id":"https://openalex.org/C67705224","wikidata":"https://www.wikidata.org/wiki/Q11053","display_name":"RNA","level":3,"score":0.10144901275634766},{"id":"https://openalex.org/C161223559","wikidata":"https://www.wikidata.org/wiki/Q138864","display_name":"Helicase","level":4,"score":0.0}],"mesh":[{"descriptor_ui":"D002453","descriptor_name":"Cell Cycle","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D002453","descriptor_name":"Cell Cycle","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D002453","descriptor_name":"Cell Cycle","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D002478","descriptor_name":"Cells, Cultured","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D002478","descriptor_name":"Cells, Cultured","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D002478","descriptor_name":"Cells, Cultured","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D002875","descriptor_name":"Chromosomes","qualifier_ui":"Q000648","qualifier_name":"ultrastructure","is_major_topic":false},{"descriptor_ui":"D002875","descriptor_name":"Chromosomes","qualifier_ui":"Q000648","qualifier_name":"ultrastructure","is_major_topic":false},{"descriptor_ui":"D002875","descriptor_name":"Chromosomes","qualifier_ui":"Q000648","qualifier_name":"ultrastructure","is_major_topic":false},{"descriptor_ui":"D002999","descriptor_name":"Clone Cells","qualifier_ui":"Q000648","qualifier_name":"ultrastructure","is_major_topic":false},{"descriptor_ui":"D002999","descriptor_name":"Clone Cells","qualifier_ui":"Q000648","qualifier_name":"ultrastructure","is_major_topic":false},{"descriptor_ui":"D002999","descriptor_name":"Clone Cells","qualifier_ui":"Q000648","qualifier_name":"ultrastructure","is_major_topic":false},{"descriptor_ui":"D005260","descriptor_name":"Female","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D005260","descriptor_name":"Female","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D005260","descriptor_name":"Female","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D009030","descriptor_name":"Mosaicism","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D009030","descriptor_name":"Mosaicism","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D009030","descriptor_name":"Mosaicism","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D012867","descriptor_name":"Skin","qualifier_ui":"Q000648","qualifier_name":"ultrastructure","is_major_topic":false},{"descriptor_ui":"D012867","descriptor_name":"Skin","qualifier_ui":"Q000648","qualifier_name":"ultrastructure","is_major_topic":false},{"descriptor_ui":"D012867","descriptor_name":"Skin","qualifier_ui":"Q000648","qualifier_name":"ultrastructure","is_major_topic":false},{"descriptor_ui":"D014178","descriptor_name":"Translocation, Genetic","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D014178","descriptor_name":"Translocation, Genetic","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D014178","descriptor_name":"Translocation, Genetic","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D014898","descriptor_name":"Werner Syndrome","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":false},{"descriptor_ui":"D014898","descriptor_name":"Werner Syndrome","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":false},{"descriptor_ui":"D014898","descriptor_name":"Werner Syndrome","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":false}],"locations_count":2,"locations":[{"id":"doi:10.1159/000131597","doi":"https://doi.org/10.1159/000131597","is_oa":false,"landing_page_url":"https://doi.org/10.1159/000131597","pdf_url":null,"source":{"id":"https://openalex.org/S4210179014","display_name":"Cytogenetics and Cell Genetics","issn_l":"0301-0171","issn":["0301-0171","1421-9816"],"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":["norway-1"],"host_organization":"https://openalex.org/P4310317820","host_organization_name":"Karger Publishers","host_organization_lineage":["https://openalex.org/P4310317820"],"host_organization_lineage_names":["Karger Publishers"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Cytogenetics and Cell Genetics","raw_type":"journal-article"},{"id":"pmid:7273855","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/7273855","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Cytogenetics and cell genetics","raw_type":"Journal Article"}],"best_oa_location":null,"sustainable_development_goals":[{"score":0.5683000087738037,"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being"}],"sustainable_development_goals_aurora":[],"study_designs":[],"awards":[{"id":"https://openalex.org/G4719558030","display_name":"Mitochondrial Protective Interventions, Aging and Healthspan","funder_award_id":"P01AG001751","funder_id":"https://openalex.org/F4320337337","funder_display_name":"National Institute on Aging"},{"id":"https://openalex.org/G8662582434","display_name":"CENTER FOR INHERITED DISEASES","funder_award_id":"5p50gm015253-22","funder_id":"https://openalex.org/F4320332161","funder_display_name":"National Institutes of Health"}],"funders":[{"id":"https://openalex.org/F4320332161","display_name":"National Institutes of Health","ror":"https://ror.org/01cwqze88"},{"id":"https://openalex.org/F4320337337","display_name":"National Institute on Aging","ror":"https://ror.org/049v75w11"}],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":0,"referenced_works":[],"related_works":["https://openalex.org/W2727209449","https://openalex.org/W1964550937","https://openalex.org/W2091170248","https://openalex.org/W3040925650","https://openalex.org/W2063403070","https://openalex.org/W113158897","https://openalex.org/W2184568292","https://openalex.org/W2307643936","https://openalex.org/W2026518911","https://openalex.org/W2414674028"],"abstract_inverted_index":{"Skin":[0],"fibroblast-like":[1],"(FL)":[2],"cells":[3,30,177],"from":[4],"patients":[5],"with":[6,157,162,171],"Werner's":[7],"syndrome":[8],"(adult":[9],"progeria)":[10],"demonstrate":[11],"multiple,":[12],"stable,":[13],"structural":[14],"chromosome":[15],"rearrangements":[16],"(variegated":[17],"translocation":[18],"mosaicism)":[19],"which":[20,75],"can":[21],"be":[22],"used":[23],"to":[24],"identify":[25],"cytogenetically":[26,37],"marked":[27],"clones":[28,65,105],"of":[29,63,69,85,100,135,146],"within":[31],"a":[32,56,81,181],"mass":[33,71,126],"culture.":[34,114],"We":[35],"have":[36,142],"followed":[38],"eight":[39],"FL":[40,176],"cell":[41],"strains":[42],"(from":[43],"two":[44,93,101],"patients)":[45],"throughout":[46],"their":[47],"entire":[48],"in":[49,92,111,125,147,163,178,185],"vitro":[50,148,179],"replicative":[51],"lifespans,":[52],"and":[53,61,66,121,166],"we":[54],"show":[55],"correlation":[57],"between":[58],"the":[59,67,70,97,112,133,158,172],"expansion":[60],"attenuation":[62,123],"individual":[64],"growth":[68],"cultures.":[72],"One":[73],"strain,":[74],"was":[76],"aged":[77],"several":[78],"times,":[79],"demonstrated":[80],"generally":[82],"reproducible":[83],"pattern":[84],"clonal":[86,119,122],"succession":[87,120],"but,":[88],"surprisingly,":[89],"also":[90],"demonstrated,":[91],"parallel":[94],"derivative":[95],"cultures,":[96,127],"late":[98],"emergence":[99],"relatively":[102],"rapidly":[103],"growing":[104],"that":[106,118,174],"had":[107,129],"not":[108],"been":[109,130],"observed":[110],"parental":[113],"These":[115],"observations":[116],"suggest":[117],"occur":[124],"as":[128],"predicted":[131],"on":[132],"basis":[134],"dilute-plating":[136],"cloning":[137],"experiments.":[138],"Our":[139],"results":[140],"may":[141],"implications":[143],"for":[144,183],"models":[145],"cellular":[149],"senescence.":[150],"In":[151],"addition,":[152],"there":[153],"are":[154],"interesting":[155],"parallels":[156],"tissue":[159],"hyperplasia":[160,184],"associated":[161],"vivo":[164],"aging,":[165],"this":[167],"observation":[168],"is":[169],"compatible":[170],"suggestion":[173],"skin":[175],"provide":[180],"model":[182],"vivo.":[186]},"counts_by_year":[{"year":2026,"cited_by_count":1},{"year":2025,"cited_by_count":1},{"year":2019,"cited_by_count":1},{"year":2017,"cited_by_count":2},{"year":2015,"cited_by_count":1},{"year":2014,"cited_by_count":1},{"year":2012,"cited_by_count":1}],"updated_date":"2026-10-16T09:59:22.235173","created_date":"2016-06-24T00:00:00"}