{"doi":"10.1002/bies.70026","title":"Liquid Guardians: Biomolecular Condensates Shield Heterochromatin Against Cellular Senescence","abstract":"<jats:title>ABSTRACT</jats:title><jats:p>Heterochromatin, a crucial constituent of the eukaryotic nucleus with highly conserved and transcriptionally silenced characteristics, plays a pivotal role in safeguarding genome stability, regulating nuclear morphology, and mediating cell fate. Recent convincing evidence indicates that the formation and maintenance of heterochromatin are implicated in cellular senescence and age‐associated disorders. Interestingly, an attractive mechanism involving liquid–liquid phase separation (LLPS) may exert a central role in regulating heterochromatin formation and maintenance. In this review, we provide an overview of recent research to illustrate the role and regulatory mechanism of the biomolecular condensates in the regulation of heterochromatin stabilization. In addition, we elucidate how heterochromatin loss contributes to cellular senescence by triggering genome instability, and explore the potential therapeutic strategies to counteract cellular senescence and age‐related pathologies by restoring heterochromatin stability. Finally, we outline current research challenges and future directions aimed at achieving a more comprehensive understanding of the link among heterochromatin regulation, phase separation, and cellular senescence, for ameliorating the effects of ageing in the future.</jats:p>","journal":"BioEssays","year":2025,"id":610115,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"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":1568512,"name":"Ze‐Guang Han","orcid":"0000-0002-1018-1752","position":1,"is_corresponding":false},{"id":300646,"name":"Jia Xie","orcid":"0000-0002-7978-1975","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Liquid Guardians: Biomolecular Condensates Shield Heterochromatin Against Cellular Senescence","abstract":"<jats:title>ABSTRACT</jats:title><jats:p>Heterochromatin, a crucial constituent of the eukaryotic nucleus with highly conserved and transcriptionally silenced characteristics, plays a pivotal role in safeguarding genome stability, regulating nuclear morphology, and mediating cell fate. Recent convincing evidence indicates that the formation and maintenance of heterochromatin are implicated in cellular senescence and age‐associated disorders. Interestingly, an attractive mechanism involving liquid–liquid phase separation (LLPS) may exert a central role in regulating heterochromatin formation and maintenance. In this review, we provide an overview of recent research to illustrate the role and regulatory mechanism of the biomolecular condensates in the regulation of heterochromatin stabilization. In addition, we elucidate how heterochromatin loss contributes to cellular senescence by triggering genome instability, and explore the potential therapeutic strategies to counteract cellular senescence and age‐related pathologies by restoring heterochromatin stability. Finally, we outline current research challenges and future directions aimed at achieving a more comprehensive understanding of the link among heterochromatin regulation, phase separation, and cellular senescence, for ameliorating the effects of ageing in the future.</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":"40474408","pmcid":null,"openalex_id":"https://openalex.org/W4411108973","authors":[],"funders":[{"funder_name":"National Key Research and Development Program of China","grant_id":"2022YFA1302700","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"82073116","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"82272969","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"82472880","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"82441040","title":null},{"funder_name":"Natural Science Foundation of Shanghai Municipality","grant_id":"21JC1403200","title":null},{"funder_name":"Higher Education Discipline Innovation Project","grant_id":"B17029","title":null},{"funder_name":"Fundamental Research Funds for the Central Universities","grant_id":"","title":null},{"funder_name":"Fundamental Research Funds for the Central Universities","grant_id":"","title":null}],"total_grants":9,"fwci":0.0,"citation_percentile":0.07889833,"influential_citations":0,"citation_trend":[],"oa_status":"closed","license":"http://onlinelibrary.wiley.com/termsAndConditions#vor","oa_locations":[{"url":"https://onlinelibrary.wiley.com/doi/pdf/10.1002/bies.70026","host_type":"publisher"},{"url":"https://doi.org/10.1002/bies.70026","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/40474408","host_type":"repository"}],"fields_of_study":["Genomics and Chromatin Dynamics","RNA Research and Splicing","RNA modifications and cancer","Heterochromatin","Cellular Senescence","Humans","Biomolecular Condensates","Animals","Genomic Instability"],"mesh_terms":["Biomolecular Condensates","Animals","Heterochromatin","Humans","Cellular Senescence","Genomic Instability"],"keywords":["Heterochromatin","Biology","Senescence","Heterochromatin protein 1","Cell biology","Mechanism (biology)","Genome instability","Genetics","DNA damage","DNA","Chromatin","Cellular senescence","Liquid—liquid Phase Separation"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-31T19:33:55.602749Z","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":[]}