{"id":"https://openalex.org/W2083765890","doi":"https://doi.org/10.1093/gerona/58.9.b776","title":"Commentary: Cell Senescence: An Evaluation of Replicative Senescence in Culture as a Model for Cell Aging In Situ","display_name":"Commentary: Cell Senescence: An Evaluation of Replicative Senescence in Culture as a Model for Cell Aging In Situ","publication_year":2003,"publication_date":"2003-09-01","ids":{"openalex":"https://openalex.org/W2083765890","doi":"https://doi.org/10.1093/gerona/58.9.b776","mag":"2083765890","pmid":"https://pubmed.ncbi.nlm.nih.gov/14528030"},"language":"en","primary_location":{"id":"doi:10.1093/gerona/58.9.b776","doi":"https://doi.org/10.1093/gerona/58.9.b776","is_oa":false,"landing_page_url":"https://doi.org/10.1093/gerona/58.9.b776","pdf_url":null,"source":{"id":"https://openalex.org/S969433497","display_name":"The Journals of Gerontology Series A","issn_l":"1079-5006","issn":["1079-5006","1758-535X"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-b","doyens","erih-plus","jufo-3","ki-jl-2","medline","norway-2","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310311648","host_organization_name":"Oxford University Press","host_organization_lineage":["https://openalex.org/P4310311648","https://openalex.org/P4310311647"],"host_organization_lineage_names":["Oxford University Press","University of Oxford"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","raw_type":"journal-article"},"volume":null,"type":"editorial","is_traditional":true,"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/A5055763114","display_name":"Vincent J. Cristofalo","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I182321934","display_name":"Lankenau Institute for Medical Research","ror":"https://ror.org/030g3hg75","country_code":"US","type":"nonprofit","lineage":["https://openalex.org/I182321934"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"V. J. Cristofalo","raw_affiliation_strings":["The Lankenau Institute for Medical Research, Wynnewood, Pennsylvania 19096, USA. cristofalov@mlhs.org","The Lankenau Institute for Medical Research, Wynnewood, Pennsylvania 19096, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"The Lankenau Institute for Medical Research, Wynnewood, Pennsylvania 19096, USA. cristofalov@mlhs.org","institution_ids":["https://openalex.org/I182321934"]},{"raw_affiliation_string":"The Lankenau Institute for Medical Research, Wynnewood, Pennsylvania 19096, USA","institution_ids":["https://openalex.org/I182321934"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5110880011","display_name":"Jeanne C. Beck","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I2801875870","display_name":"Coriell Institute For Medical Research","ror":"https://ror.org/04npwsp41","country_code":"US","type":"nonprofit","lineage":["https://openalex.org/I2801875870"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"J. Beck","raw_affiliation_strings":["The Coriell Institute for Medical Research, Camden, New Jersey"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"The Coriell Institute for Medical Research, Camden, New Jersey","institution_ids":["https://openalex.org/I2801875870"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5110456210","display_name":"Robert G. Allen","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"R. G. Allen","raw_affiliation_strings":["The Sally Balin Medical Center, Media, Pennsylvania"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"The Sally Balin Medical Center, Media, Pennsylvania","institution_ids":[]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":2,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":{"value":4408,"currency":"USD","value_usd":4408},"apc_paid":null,"fwci":null,"has_fulltext":false,"cited_by_count":21,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":"58","issue":"9","first_page":"B776","last_page":"B779"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10937","display_name":"Telomeres, Telomerase, and Senescence","score":0.9990000128746033,"subfield":{"id":"https://openalex.org/subfields/1307","display_name":"Cell 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"}},"topics":[{"id":"https://openalex.org/T10937","display_name":"Telomeres, Telomerase, and Senescence","score":0.9990000128746033,"subfield":{"id":"https://openalex.org/subfields/1307","display_name":"Cell 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"}},{"id":"https://openalex.org/T10676","display_name":"Genetics, Aging, and Longevity in Model Organisms","score":0.0008999999845400453,"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/T11265","display_name":"Aging and Gerontology Research","score":0.0,"subfield":{"id":"https://openalex.org/subfields/3204","display_name":"Developmental and Educational Psychology"},"field":{"id":"https://openalex.org/fields/32","display_name":"Psychology"},"domain":{"id":"https://openalex.org/domains/2","display_name":"Social Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/replicative-senescence","display_name":"replicative senescence","score":0.9010000228881836},{"id":"https://openalex.org/keywords/cellular-senescence","display_name":"cellular senescence","score":0.8759999871253967},{"id":"https://openalex.org/keywords/replicative-lifespan","display_name":"replicative lifespan","score":0.7919999957084656},{"id":"https://openalex.org/keywords/dermal-fibroblasts","display_name":"dermal fibroblasts","score":0.8840000033378601},{"id":"https://openalex.org/keywords/donor-age","display_name":"donor age","score":0.8349999785423279},{"id":"https://openalex.org/keywords/colony-size-distribution","display_name":"colony size distribution","score":0.8489999771118164},{"id":"https://openalex.org/keywords/proliferative-potential","display_name":"proliferative capacity","score":0.75},{"id":"https://openalex.org/keywords/sex-differences","display_name":"sex differences","score":0.45100000500679016}],"concepts":[{"id":"https://openalex.org/C522857546","wikidata":"https://www.wikidata.org/wiki/Q2070979","display_name":"Senescence","level":2,"score":0.9225989580154419},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.4764466881752014},{"id":"https://openalex.org/C2779523775","wikidata":"https://www.wikidata.org/wiki/Q9075999","display_name":"Cellular senescence","level":4,"score":0.4752644896507263},{"id":"https://openalex.org/C81885089","wikidata":"https://www.wikidata.org/wiki/Q189082","display_name":"Cell culture","level":2,"score":0.46308523416519165},{"id":"https://openalex.org/C2777822432","wikidata":"https://www.wikidata.org/wiki/Q216681","display_name":"In situ","level":2,"score":0.44009560346603394},{"id":"https://openalex.org/C1491633281","wikidata":"https://www.wikidata.org/wiki/Q7868","display_name":"Cell","level":2,"score":0.41170114278793335},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.40801069140434265},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.2016168236732483},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.19808581471443176},{"id":"https://openalex.org/C127716648","wikidata":"https://www.wikidata.org/wiki/Q104053","display_name":"Phenotype","level":3,"score":0.07485979795455933},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.05125516653060913},{"id":"https://openalex.org/C178790620","wikidata":"https://www.wikidata.org/wiki/Q11351","display_name":"Organic chemistry","level":1,"score":0.0}],"mesh":[{"descriptor_ui":"D000328","descriptor_name":"Adult","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D000368","descriptor_name":"Aged","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D000369","descriptor_name":"Aged, 80 and over","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D000375","descriptor_name":"Aging","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":false},{"descriptor_ui":"D000375","descriptor_name":"Aging","qualifier_ui":"Q000502","qualifier_name":"physiology","is_major_topic":true},{"descriptor_ui":"D002455","descriptor_name":"Cell Division","qualifier_ui":"Q000502","qualifier_name":"physiology","is_major_topic":false},{"descriptor_ui":"D002468","descriptor_name":"Cell Physiological Phenomena","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D002470","descriptor_name":"Cell Survival","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":"D005069","descriptor_name":"Evaluation Studies as Topic","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":"D005347","descriptor_name":"Fibroblasts","qualifier_ui":"Q000166","qualifier_name":"cytology","is_major_topic":true},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008136","descriptor_name":"Longevity","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008297","descriptor_name":"Male","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008875","descriptor_name":"Middle Aged","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008954","descriptor_name":"Models, Biological","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D012680","descriptor_name":"Sensitivity and Specificity","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D016922","descriptor_name":"Cellular Senescence","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":false},{"descriptor_ui":"D016922","descriptor_name":"Cellular Senescence","qualifier_ui":"Q000502","qualifier_name":"physiology","is_major_topic":true},{"descriptor_ui":"D016923","descriptor_name":"Cell Death","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true}],"locations_count":4,"locations":[{"id":"doi:10.1093/gerona/58.9.b776","doi":"https://doi.org/10.1093/gerona/58.9.b776","is_oa":false,"landing_page_url":"https://doi.org/10.1093/gerona/58.9.b776","pdf_url":null,"source":{"id":"https://openalex.org/S969433497","display_name":"The Journals of Gerontology Series A","issn_l":"1079-5006","issn":["1079-5006","1758-535X"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-b","doyens","erih-plus","jufo-3","ki-jl-2","medline","norway-2","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310311648","host_organization_name":"Oxford University Press","host_organization_lineage":["https://openalex.org/P4310311648","https://openalex.org/P4310311647"],"host_organization_lineage_names":["Oxford University Press","University of Oxford"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"The Journals of Gerontology Series A: Biological Sciences and Medical Sciences","raw_type":"journal-article"},{"id":"pmid:14528030","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/14528030","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":"The journals of gerontology. Series A, Biological sciences and medical sciences","raw_type":"Journal Article"},{"id":"pmh:oai:CiteSeerX.psu:10.1.1.1006.8171","doi":null,"is_oa":false,"landing_page_url":"http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.1006.8171","pdf_url":null,"source":null,"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"http://biomedgerontology.oxfordjournals.org/content/58/9/B776.full.pdf","raw_type":"text"},{"id":"pmh:oai:CiteSeerX.psu:10.1.1.1034.614","doi":null,"is_oa":false,"landing_page_url":"http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.1034.614","pdf_url":null,"source":null,"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"http://biomedgerontology.oxfordjournals.org/content/58/9/B776.full.pdf%2Bhtml?frame%3Dsidebarc58/9/B776","raw_type":"text"}],"best_oa_location":null,"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","score":0.5683000087738037,"display_name":"Good health and well-being"}],"study_designs":[],"awards":[{"id":"https://openalex.org/G2123151222","display_name":null,"funder_award_id":"AG00378","funder_id":"https://openalex.org/F4320337337","funder_display_name":"National Institute on Aging"},{"id":"https://openalex.org/G308169915","display_name":"Regulation of the MAP Kinase Pathway in Senescence","funder_award_id":"R01AG020955","funder_id":"https://openalex.org/F4320337337","funder_display_name":"National Institute on Aging"},{"id":"https://openalex.org/G6820492039","display_name":null,"funder_award_id":"N01AG02101","funder_id":"https://openalex.org/F4320337337","funder_display_name":"National Institute on Aging"}],"funders":[{"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":23,"referenced_works":["https://openalex.org/W159681246","https://openalex.org/W1846860192","https://openalex.org/W1975502679","https://openalex.org/W1977201664","https://openalex.org/W1989476856","https://openalex.org/W1990063230","https://openalex.org/W1992083500","https://openalex.org/W1995906420","https://openalex.org/W1998663807","https://openalex.org/W2004314923","https://openalex.org/W2006679659","https://openalex.org/W2011482325","https://openalex.org/W2018686812","https://openalex.org/W2019172307","https://openalex.org/W2047330128","https://openalex.org/W2051146905","https://openalex.org/W2071673220","https://openalex.org/W2080612757","https://openalex.org/W2087404852","https://openalex.org/W2121739926","https://openalex.org/W2126086581","https://openalex.org/W2164719183","https://openalex.org/W2338523136"],"related_works":["https://openalex.org/W7096267864","https://openalex.org/W1848078943","https://openalex.org/W2136841859","https://openalex.org/W3125944806","https://openalex.org/W2118656895","https://openalex.org/W4205099793","https://openalex.org/W2106774689","https://openalex.org/W2078601089","https://openalex.org/W2072730583","https://openalex.org/W2051146905"],"abstract_inverted_index":{"THE":[0],"limited":[1],"replicative":[2,100,147,182,206,220,289,321,333,343,369,381,423,469,534,543,561,698,707,751,799,908,950,970,1011,1065,1187,1312,1341,1469,1501,1632,1671,1784,1920,1931,1944,1975,2230,2242,2252,2269],"life":[3,221,252,290,322,334,344,370,382,424,433,470,535,562,699,708,745,752,777,800,909,951,971,990,998,1012,1066,1137,1168,1188,1222,1238,1313,1342,1470,1502,1601,1807,1894,1921,1945,1976,2031,2220,2231,2243,2253,2270],"span":[4,222,253,323,345,383,471,536,563,709,746,753,778,801,952,972,991,999,1189,1223,1343,1471,1503,1602,1808,1922,1946,1977,2032,2221,2232,2244,2254,2271],"of":[5,18,44,54,75,78,99,120,126,139,159,172,189,195,199,205,223,235,247,261,277,296,324,342,349,389,394,402,453,515,521,537,545,556,601,607,616,635,669,703,710,726,741,759,786,817,827,845,888,907,911,949,965,968,988,1015,1079,1134,1150,1190,1199,1240,1257,1273,1297,1302,1310,1380,1421,1485,1508,1517,1555,1582,1615,1631,1645,1648,1681,1737,1779,1826,1843,1851,1892,1915,1923,1958,1973,1987,2041,2058,2069,2076,2107,2112,2115,2140,2148,2165,2191,2198,2205,2219],"fibroblasts":[6,225,711,1924,2095],"derived":[7,356,1085,1096,1117,1370],"from":[8,357,409,412,575,1006,1047,1086,1097,1118,1214,1243,1307,1321,1371,1388,1522,1543,1618,1635,1670,1740,1882,2235,2286,2298],"various":[9],"human":[10,473,1593,2099,2153],"tissues":[11,1762],"is":[12,23,50,71,112,135,175,459,500,564,689,714,717,721,834,962,1101,1179,1234,1354,1410,1482,1667,1765,1875,1966,2013,2047],"commonly":[13],"studied":[14],"as":[15,104,232,346,435,591,692,1111,1113,1443,1652,1654,1855,1857,1888,1952,2055,2073,2195],"a":[16,32,51,72,105,233,283,347,362,428,538,608,613,693,742,783,912,946,976,994,1155,1159,1197,1218,1231,1282,1364,1586,1664,1701,1816,1883,1902,2049,2056,2074,2123,2129,2138],"model":[17,106,265,2012,2057,2075,2155],"biological":[19,1479],"aging":[20,30,164,1785,1965,2077,2170],"(1,2).":[21],"There":[22],"little":[24,963],"doubt":[25],"that":[26,122,128,134,299,457,493,532,572,661,687,719,762,832,848,928,1026,1075,1093,1152,1174,1212,1230,1289,1336,1356,1376,1461,1531,1551,1559,1596,1638,1643,1666,1685,1696,1752,1783,1794,1801,1994,2007,2117,2179],"organismic":[27,267,1964],"failures":[28],"in":[29,37,57,87,90,93,102,110,131,160,165,181,192,211,218,230,327,367,481,502,549,652,671,712,755,811,975,1021,1104,1327,1384,1404,1412,1585,1627,1657,1708,1717,1733,1760,1763,1862,1878,1889,1925,1933,1947,1960,1985,1988,2096,2128,2173],"have":[31,280,640,795,1073,1153,1529,1641,1865],"cellular":[33,108,2163,2169],"basis.":[34],"Replicative":[35],"senescence":[36,101,127,148,183,191,207,210,1633,2011,2072],"culture":[38,62,231,264,523,539,713,1621,1659,1742,1926,1962,2010,2044,2054,2071,2097],"fits":[39],"the":[40,58,61,97,117,137,140,150,157,177,185,196,202,215,219,259,262,293,319,336,379,387,413,436,482,513,519,533,541,546,550,554,576,585,588,599,629,638,666,672,675,705,739,760,787,805,825,856,859,897,935,956,966,969,997,1009,1027,1039,1048,1056,1076,1132,1135,1144,1148,1163,1183,1186,1254,1271,1300,1322,1377,1408,1418,1453,1495,1505,1514,1518,1523,1553,1560,1571,1579,1612,1616,1620,1629,1636,1646,1658,1674,1691,1731,1741,1753,1776,1823,1840,1848,1852,1858,1890,1896,1919,1928,1939,1955,1971,2008,2022,2039,2042,2062,2113,2120,2146,2152,2162,2196,2214,2287,2299],"description":[41],"and":[42,92,187,288,305,376,404,446,451,462,484,489,508,595,731,750,829,902,980,1008,1032,1064,1108,1202,1229,1275,1304,1358,1428,1463,1489,1526,1805,1828,1835,1845,1907,1935,1949,2029,2067,2086,2102,2125,2142,2189,2203,2208,2284,2293],"definition":[43],"cell":[45,80,190,209,228,263,522,602,889,915,937,1045,1172,1241,1317,1381,2009,2043,2053,2070,2108,2187,2236,2260],"senescence;":[46],"with":[47,82,397,468,765,836,1139,1252,1270,1390,1432,1452,1590,1767],"subcultivation,":[48,581],"there":[49,70,426,458,477,961,1546],"gradual":[52,73],"loss":[53,2190],"proliferative":[55,88,251,667,776,846,879,989,1221,1366,1424,1515,1613,1806,1824,1893,2030,2087,2265],"capacity":[56,544,600,1516,1614,1825,1932,2088],"population":[59,551,620,1520,1574,1581,2278],"until":[60],"can":[63,1662,1677,1689],"no":[64,339,463,1059,1532,1913],"longer":[65,1167],"be":[66,768,1036,1128,1399,1448,1549,1606,1678,1700,1721,1787,1998,2183],"subcultivated.":[67],"In":[68,269,292,1068,1497,1838,1911,1969,2060,2150],"vivo,":[69],"attenuation":[74],"proliferation":[76,1487],"rates":[77,1078],"some":[79,124,479,1191,1655,2004,2166],"types":[81],"age,":[83],"suggesting":[84],"parallel":[85],"changes":[86,109,178,1656,2116,2171],"regulation":[89],"vivo":[91,111,166,1328,1764],"vitro":[94,103,161,1934,1948,1990],"(3).":[95],"Thus":[96],"study":[98,819,1793,2111],"for":[107,201,257,373,386,421,472,525,680,695,774,798,808,1094,1131,1170,1316,1368,1705,1860,1954,2016,2051,2136,2160,2176,2311],"attractive":[113],"since":[114],"it":[115,655,716,720,1353,1510,2046],"brings":[116],"experimental":[118],"advantage":[119],"cells":[121,571,639,670,1369,1536,1584,1707,1719,2121],"exhibit":[123,1217],"features":[125],"are":[129,478,632,893,1245,1426,1537,1564,2134],"maintained":[130],"an":[132,723,1286,1333,1483],"environment":[133,1660],"under":[136,391,1294],"control":[138],"investigator.":[141],"Despite":[142],"numerous":[143],"published":[144,772,2091],"studies":[145,162,272,298,524,906,1256,1272,1309,1959,2017],"on":[146,512,527,792,862,934,1052,1292,1423,2018,2290],"over":[149,399,649],"last":[151],"40":[152],"years":[153,393,401,1124,1296],"(e.g.,":[154],"Ref.":[155],"3),":[156],"relevance":[158,260,1630],"to":[163,208,241,250,266,331,504,510,518,560,582,604,659,737,858,878,896,985,1038,1263,1280,1331,1349,1362,1398,1450,1467,1499,1512,1592,1610,1723,1730,1746,1775,1812,1847,1899,1963,2005,2037,2145,2213,2264,2303],"has":[167,213,254,1756,2033,2156],"been":[168,214,255,796,1758,2034,2090,2158],"controversial.":[169],"The":[170,815,869,1208,1683,1750,1992,2105,2227,2251,2267,2308],"question":[171,964],"major":[173,197,310],"interest":[174],"whether":[176],"we":[179,494,685,1071],"observe":[180,1281,1363],"duplicate":[184],"pathways":[186],"mechanisms":[188,2114,2167,2185,2215],"situ.":[193],"One":[194,1792],"sources":[198],"support":[200,738,1901,2038],"direct":[203,775,1956,2259],"relationship":[204,246,284,1903,1929,1942,1996,2025,2082,2228],"situ":[212],"putative":[216,302,2023],"decline":[217,341,366,1335],"skin":[224,1082],"(and":[226],"other":[227,490,586,2209],"types)":[229],"function":[234,348,2193],"donor":[236,248,286,350,558,727,1266,1434,1813,1833,1905,1936,1950,2027,2084],"age":[237,249,287,395,466,559,1267,1287,1435,1834,1906,1951,2028,2085],"(4,5).":[238],"However,":[239,352,679,2020],"failure":[240,1745],"consistently":[242],"show":[243],"this":[244,301,818,1697,1768,1796,1867,1995],"inverse":[245,2024],"problematic":[256],"defining":[258],"aging.":[268,528,2019,2059,2149,2217],"fact,":[270,1839,2061,2151],"several":[271,681,758,1639],"(6\u20138)":[273],"using":[274,329,770,884,1182,2052],"healthy":[275,1258,1761],"donors":[276,390,437,1088,1119,1259],"different":[278,417,923,932,1326,1687],"ages":[279,418,1329],"not":[281,633,690,722,823,993,1250,1338,1576,2014,2048],"demonstrated":[282,1999],"between":[285,486,744,996,1062,1106,1115,1822,1832,1904,1930,1943,2026,2083,2229],"span.":[291,700,1067],"most":[294],"recent":[295],"these":[297,506,516,1458,1748],"address":[300,2180],"relationship,":[303],"Smith":[304,487,594,730,828,852,1031,1303,1357],"colleagues":[306,596,732,830,903,981,1033,1276,1305,1359,1527],"(6)":[307,488,597,733,831,1034,1306,1360],"make":[308],"four":[309],"points:":[311],"(a)":[312],"colony":[313,2247],"size":[314,611,1157,2248],"distribution":[315,2249],"(CSD)":[316],"analysis":[317],"estimates":[318,844],"total":[320,697,706,1378,1580,1599,1974],"fibroblasts;":[325],"(b)":[326,442],"cultures":[328,355,407,475,794,857,1016,1084,1095,1110,1116,1213,1386,1563,2109,2133],"CSD":[330,589,630,662,688,749,766,803,833,843,1002,1063,1145,1184,1454,1462,1481,1604,1979],"estimate":[332,1484],"span,":[335,425,1895],"authors":[337,491,1209,1640],"report":[338,1211],"significant":[340,365,465,1060],"age.":[351,728,1298,1814,1937],"when":[353,406,853,1236,1340,1608],"comparing":[354,557],"females":[358],"only,":[359],"they":[360,763,1041],"detected":[361],"small":[363],"but":[364,992,1476],"estimated":[368,380,422,747,1000,1136,1220,1311,2245,2268],"span;":[371],"(c)":[372],"both":[374,1103,1802],"male":[375],"female":[377],"donors,":[378],"was":[384,427,1194,1290,1337,1344,1402,1622,1820,2078,2256,2272],"greater":[385,1219,1411],"pool":[388],"30":[392,400,1295],"compared":[396,797],"those":[398,452,1140],"age;":[403],"(d)":[405],"established":[408,1319,1387,1566,1881],"sequential":[410],"biopsies":[411],"same":[414,788,936,1323],"individuals":[415,1293,1324,1389],"at":[416,804,867,919,1325,2238,2262],"were":[419,849,873,917,983,1054,1089,1809],"evaluated":[420],"nonsignificant":[429],"trend":[430,1233],"toward":[431],"shorter":[432],"spans":[434,910,1013,1138,1169,1239,1314],"grew":[438],"older.":[439],"Although":[440,729],"finding":[441],"above":[443],"essentially":[444,894],"confirms":[445],"extends":[447],"our":[448,1022],"findings":[449,517],"(7)":[450,982,1072],"others":[454,1374],"(8),":[455],"namely,":[456],"large":[460,784,1841],"variability":[461],"statistically":[464],"association":[467],"fibroblast":[474,914,1083,1385,1961,2154],"(7,8),":[476,1260],"differences":[480,507,1105,1114],"data":[483,736,953,1005,1057,1301,1897,2222],"interpretation":[485,1554,1869,1986],"(7,8)":[492],"think":[495],"require":[496],"clarification.":[497],"This":[498,944,1100,1126,1247],"commentary":[499],"written":[501],"part":[503],"clarify":[505],"also":[509,1210,2175,2297],"comment":[511],"implications":[514],"role":[520],"research":[526],"Existing":[529],"evidence":[530,1859,1953],"indicates":[531,945],"reflects":[540,665],"maximum":[542,870],"longest-lived":[547],"clone":[548],"(9).":[552],"Thus,":[553,1589,1673,1887,1938],"procedure":[555],"confounded":[565],"by":[566,593,628,748,851,875,881,900,921,931,940,955,1001,1018,1030,1196,1347,1789,1978,2065,2224,2246,2258,2274,2281],"selection":[567,636,1861],"pressures":[568],"against":[569],"slower-growing":[570],"take":[573],"place":[574],"first":[577],"outgrowth,":[578],"through":[579],"serial":[580,676,876,957,1019,1464,1863],"senescence.":[583,1672],"On":[584],"hand,":[587],"assay":[590,1164],"used":[592,2036],"evaluates":[598],"populations":[603,626,645],"form":[605],"colonies":[606,1151],"certain":[609,1649],"minimal":[610],"within":[612,1158],"defined":[614],"period":[615],"time":[617,1161],"(\u201cusually":[618],"before":[619,2080],"doubling":[621,2279],"[PDL]":[622],"10\u201d)":[623],"(6).":[624],"While":[625],"examined":[627,1538,1795],"method":[631,694,887,1146,1914],"free":[634],"effects,":[637],"experienced":[641],"\u201cless":[642],"selection\u201d":[643],"than":[644,674,942,1092,1224,1401,1831],"subcultivated":[646],"multiple":[647,1879],"times":[648],"long":[650],"periods":[651],"culture.":[653,1496],"Therefore,":[654],"might":[656],"seem":[657],"safe":[658],"conclude":[660,1025,2006],"more":[663,1176,1430],"accurately":[664,1577],"potential":[668,847,1367,1425],"tissue":[673,1562,1587,1617],"cultivation":[677,877,1465],"method.":[678],"reasons":[682],"(see":[683],"below),":[684],"suggest":[686,1332,1460],"useful":[691],"estimating":[696,1918],"Furthermore,":[701,1417],"regardless":[702],"how":[704,1534],"determined,":[715],"evident":[718,1102],"accurate":[724],"reflection":[725],"present":[734],"compelling":[735],"existence":[740],"correlation":[743,995,1028,1061,1797,1819],"determined":[754,1017,1315,1345,2223,2233,2257,2273],"mass":[756],"culture,":[757,1718],"results":[761,816,929,1459],"obtained":[764,874,930,954],"cannot":[767,1997],"confirmed":[769,1759],"standard":[771,886],"methods":[773,892,898,1466,1595],"determination":[779],"(7).":[780,904,1125,1351],"For":[781,1871],"example,":[782,1872],"number":[785,1149,1379,1507,1842,2295],"Baltimore":[789,1049],"Longitudinal":[790,1050],"Study":[791,1051],"Aging-derived":[793],"versus":[802,1122,2241],"Coriell":[806,882,920,1203],"Institute":[807,2289,2310],"Medical":[809,2312],"Research":[810],"Camden,":[812],"New":[813],"Jersey.":[814],"(Figure":[820],"1)":[821],"do":[822],"confirm":[824],"observations":[826],"correlated":[835,1811],"actual":[837,1010,1506],"cumulative":[838,1600],"PDL.":[839],"Figure":[840],"1":[841],"depicts":[842],"submitted":[850,855],"he":[854],"National":[860,2288],"Institutes":[861],"Aging":[863,1053,1204,2291],"(NIA)":[864,2292],"Cell":[865,1205],"Bank":[866,1206],"Coriell.":[868],"PDL":[871,1081,1568,2276],"values":[872],"exhaustion":[880,1350],"technicians":[883,933],"their":[885,891,1540,1725],"cultivation;":[890],"identical":[895],"described":[899],"Cristofalo":[901,979],"Repetitive":[905],"single":[913,1884],"line":[916,938],"performed":[918],"three":[922],"technicians.":[924],"These":[925],"experiments":[926],"showed":[927],"differed":[939],"less":[941],"2%.":[943],"high":[947],"reproducibility":[948,967,987],"subcultivation":[958,1020,1348,2240,2263],"method;":[959],"thus,":[960],"data.":[973],"Similarly,":[974],"previous":[977,1069],"study,":[978],"able":[984],"document":[986],"(NIA":[1003],"Repository":[1004],"Smith)":[1007],"(PDL)":[1014],"laboratory.":[1023],"We":[1024],"found":[1029,1375,1558],"must":[1035],"peculiar":[1037],"cohort":[1040],"examined.":[1042],"When":[1043,1715],"additional":[1044,1625,1982],"lines":[1046,1173,1193,1242,1318],"evaluated,":[1055],"revealed":[1058],"studies,":[1070],"shown":[1074,1530,1642],"growth":[1077],"early":[1080],"young":[1087,1215],"significantly":[1090],"higher":[1091],"older":[1098],"donors.":[1099],"fetal-":[1107],"adult-derived":[1109],"well":[1112,1444,1653,1856],"aged":[1120,1226],"<30":[1121],">30":[1123,1227],"may":[1127,1472,1547,1605,1699,1720,1786,1980,2182],"one":[1129,1732],"basis":[1130,2164],"discrepancy":[1133],"measured":[1141],"directly.":[1142],"Since":[1143],"counts":[1147,2237],"reached":[1154],"particular":[1156],"fixed":[1160],"period,":[1162],"should":[1165],"predict":[1166],"fetal-derived":[1171],"grow":[1175],"rapidly.":[1177],"It":[1178],"informative":[1180],"that,":[1181],"method,":[1185],"fetal":[1192],"overestimated":[1195],"factor":[1198],"2":[1200,2225],"(7,":[1201],"Catalog).":[1207],"women":[1216,1225,1244],"years,":[1228],"negative":[1232],"observed":[1235,1403,1821,2172],"CSD-predicted":[1237],"plotted.":[1246],"result":[1248],"does":[1249,1575],"agree":[1251],"either":[1253,1391,1598,1735],"two":[1255,1474],"which":[1261,1446,1619,1709,1781],"failed":[1262,1279,1361],"identify":[1264],"any":[1265,2081],"effect,":[1268],"or":[1269,1285,1394,1569,1603,1711,1744,1917,2092],"Martin":[1274],"(4),":[1277],"who":[1278],"sex":[1283],"effect":[1284,1288,1409],"dependent":[1291],"Additionally,":[1299],"longitudinal":[1308],"sequentially":[1320],"appeared":[1330],"age-related":[1334],"seen":[1339],"directly":[1346,1798,2234],"Finally,":[1352],"surprising":[1355],"reduced":[1365],"diabetics":[1372],"while":[1373,2021,2119],"divisions":[1382],"possible":[1383],"type":[1392,1413],"I":[1393,1438],"II":[1395,1414],"diabetes":[1396,1415,1422,1439],"tended":[1397],"lower":[1400],"age-matched,":[1405],"nondiabetic":[1406],"controls;":[1407],"(8,10\u201312).":[1416],"deleterious":[1419],"effects":[1420,2197],"progressive":[1427],"become":[1429],"pronounced":[1431],"increasing":[1433],"(8,12).":[1436],"Type":[1437],"decreases":[1440],"plating":[1441],"efficiency":[1442],"(13),":[1445],"would":[1447],"expected":[1449],"interfere":[1451],"assay.":[1455],"Taken":[1456],"together,":[1457],"determine":[1468,1597],"measure":[1473],"different,":[1475],"perhaps":[1477],"overlapping,":[1478],"parameters.":[1480],"initial":[1486,1519,1541,1572],"rate":[1488],"cloning":[1490],"efficiency,":[1491],"soon":[1492,1535],"after":[1493,1539],"establishing":[1494],"contrast":[1498],"CSD,":[1500],"determines":[1504],"doublings":[1509],"takes":[1511],"exhaust":[1513],"emerging":[1521],"biopsy.":[1524,1588],"Balin":[1525],"(14)":[1528],"matter":[1533],"outgrowth":[1542,1573],"biopsy":[1544],"pieces,":[1545],"still":[1548],"artifacts":[1550],"complicate":[1552],"results.":[1556],"They":[1557],"way":[1561],"typically":[1565],"(for":[1567],"CSD),":[1570],"reflect":[1578,1611],"viable":[1583],"regard":[1591],"aging,":[1594],"misleading":[1607],"interpreted":[1609],"derived.":[1623],"An":[1624],"problem":[1626],"evaluating":[1628],"arises":[1634],"fact":[1637,1684,1751,1993],"modulation":[1644],"expression":[1647],"genes":[1650],"(15\u201317)":[1651],"(18\u201320)":[1661],"produce":[1663,1690],"phenotype":[1665,1676,1694,1698,1755],"apparently":[1668],"indistinguishable":[1669],"senescent":[1675,1693,1754],"achieved":[1679],"irrespective":[1680],"proliferation.":[1682],"many":[1686],"stimuli":[1688],"so-called":[1692],"suggests":[1695],"final,":[1702],"common":[1703,2184],"pathway":[1704],"replicating":[1706],"signaling":[1710,2206],"metabolic":[1712],"imbalances":[1713],"occur.":[1714],"placed":[1716],"unable":[1722],"achieve":[1724],"\u201ctrue\u201d":[1726],"differentiated":[1727],"fate":[1728],"(identical":[1729],"vivo)":[1734],"because":[1736],"signals":[1738],"missing":[1739],"medium":[1743],"process":[1747],"signals.":[1749],"never":[1757],"consistent":[1766],"view":[1769],"(18,21).":[1770],"Another":[1771],"confounding":[1772,1983],"issue":[1773],"relates":[1774],"\u201ctelomere":[1777],"hypothesis":[1778],"aging,\u201d":[1780],"proposes":[1782],"regulated":[1788],"telomere":[1790,1803,1829,1836,1873,1909],"shortening.":[1791],"(22)":[1799],"claimed":[1800],"length":[1804,1830,1874],"marginally":[1810],"Yet,":[1815],"much":[1817],"stronger":[1818],"clones":[1827,1880],"length.":[1837,1910],"variations":[1844],"exceptions":[1846],"original":[1849,1868,2063],"formulation":[1850],"Telomere":[1853],"Hypothesis,":[1854],"subcultivations,":[1864],"made":[1866],"untenable.":[1870],"highly":[1876],"variable":[1877],"individual":[1885],"(23).":[1886],"case":[1891],"fail":[1898],"clearly":[1900],"average":[1908],"summary,":[1912],"determining":[1916],"supports":[1927],"generally":[1940],"accepted":[1941],"applicability":[1957],"fundamentally":[1967],"flawed.":[1968],"addition,":[1970],"estimation":[1972],"introduce":[1981],"factors":[1984],"vivo/in":[1989],"relationships.":[1991],"reproducibly":[2000],"will":[2001],"undoubtedly":[2002],"lead":[2003],"relevant":[2015,2144],"widely":[2035],"utility":[2040],"model,":[2045],"requirement":[2050],"speculation":[2064],"Hayflick":[2066],"Moorhead":[2068],"proposed":[2079],"had":[2089],"suggested.":[2093],"Human":[2094],"express":[2098],"genetic,":[2100],"metabolic,":[2101],"regulatory":[2103],"behavior.":[2104],"use":[2106],"permits":[2110],"occur":[2118],"undergo":[2122],"predictable":[2124],"reproducible":[2126],"deterioration":[2127,2188],"constant":[2130],"environment.":[2131],"Fibroblast":[2132],"valuable":[2135,2159],"examining":[2137],"variety":[2139],"questions":[2141],"hypotheses":[2143,2178],"biology":[2147],"already":[2157],"explaining":[2161],"underlying":[2168,2186,2216],"situ;":[2174],"testing":[2177],"what":[2181],"integrative":[2192],"such":[2194],"reactive":[2199],"oxygen":[2200],"species,":[2201],"overexpression":[2202],"underexpression":[2204],"molecules,":[2207],"modulations":[2210],"particularly":[2211],"important":[2212],"Comparison":[2218],"methods.":[2226],"each":[2239],"(CSD).":[2250],"(actual)":[2255],"count":[2261],"exhaustion.":[2266],"CSD.":[2275],"=":[2277],"Supported":[2280],"grants":[2282],"AG00378":[2283],"AG20955":[2285],"contract":[2294],"N01-AG-0-2101":[2296],"NIA.":[2300],"Address":[2301],"correspondence":[2302],"Vincent":[2304],"J.":[2305],"Cristofalo,":[2306],"PhD,":[2307],"Lankenau":[2309],"Research,":[2313],"100":[2314],"Lancaster":[2315],"Avenue,":[2316],"Wynnewood,":[2317],"PA":[2318],"19096.":[2319],"E-mail:":[2320],"cristofalov@mlhs.org":[2321]},"counts_by_year":[{"year":2024,"cited_by_count":1},{"year":2023,"cited_by_count":2},{"year":2022,"cited_by_count":3},{"year":2021,"cited_by_count":1},{"year":2020,"cited_by_count":1},{"year":2019,"cited_by_count":1},{"year":2018,"cited_by_count":2},{"year":2017,"cited_by_count":1},{"year":2015,"cited_by_count":1},{"year":2013,"cited_by_count":1}],"updated_date":"2026-11-07T11:25:07.637180","created_date":"2016-06-24T00:00:00"}
