{"doi":"10.1126/science.1069523","title":"Senescence Induced by Altered Telomere State, Not Telomere Loss","abstract":"<jats:p>Primary human cells in culture invariably stop dividing and enter a state of growth arrest called replicative senescence. This transition is induced by programmed telomere shortening, but the underlying mechanisms are unclear. Here, we report that overexpression of TRF2, a telomeric DNA binding protein, increased the rate of telomere shortening in primary cells without accelerating senescence. TRF2 reduced the senescence setpoint, defined as telomere length at senescence, from 7 to 4 kilobases. TRF2 protected critically short telomeres from fusion and repressed chromosome-end fusions in presenescent cultures, which explains the ability of TRF2 to delay senescence. Thus, replicative senescence is induced by a change in the protected status of shortened telomeres rather than by a complete loss of telomeric DNA.</jats:p>","journal":"Science","year":2002,"id":605004,"datarank":14.009058122834087,"base_score":6.682108597449809,"endowment":6.682108597449809,"self_citation_contribution":1.0023162896174715,"citation_network_contribution":13.006741833216616,"self_endowment_contribution":1.0023162896174715,"citer_contribution":13.006741833216616,"corpus_percentile":null,"corpus_rank":null,"citation_count":797,"citer_count":200,"citers_with_citation_signal":200,"citers_with_endowment":200,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":486479,"name":"Agata Smogorzewska","orcid":"0000-0001-6285-1562","position":1,"is_corresponding":false},{"id":250641,"name":"Titia de Lange","orcid":"0000-0002-9267-367X","position":2,"is_corresponding":false},{"id":215683,"name":"Jan Karlseder","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Senescence Induced by Altered Telomere State, Not Telomere Loss","abstract":"<jats:p>Primary human cells in culture invariably stop dividing and enter a state of growth arrest called replicative senescence. This transition is induced by programmed telomere shortening, but the underlying mechanisms are unclear. Here, we report that overexpression of TRF2, a telomeric DNA binding protein, increased the rate of telomere shortening in primary cells without accelerating senescence. TRF2 reduced the senescence setpoint, defined as telomere length at senescence, from 7 to 4 kilobases. TRF2 protected critically short telomeres from fusion and repressed chromosome-end fusions in presenescent cultures, which explains the ability of TRF2 to delay senescence. Thus, replicative senescence is induced by a change in the protected status of shortened telomeres rather than by a complete loss of telomeric DNA.</jats:p>","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"11923537","pmcid":null,"openalex_id":null,"authors":[],"funders":[{"funder_name":"NCI NIH HHS","grant_id":"CA76027","title":null},{"funder_name":"NIA NIH HHS","grant_id":"AG16643","title":null}],"total_grants":2,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":null,"license":null,"oa_locations":[{"url":"https://www.science.org/doi/pdf/10.1126/science.1069523","host_type":"publisher"}],"fields_of_study":[],"mesh_terms":["Cells, Cultured","Cell Line","Telomere","Humans","Retroviridae","DNA-Binding Proteins","Retinoblastoma Protein","Telomeric Repeat Binding Protein 2","Oncogene Proteins, Viral","Antigens, Polyomavirus Transforming","Repressor Proteins","DNA","Cell Division","Transformation, Genetic","Tumor Suppressor Protein p53","Papillomavirus E7 Proteins","Cellular Senescence"],"keywords":[],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-30T01:23:14.017046Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}