{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T11:06:22Z","timestamp":1790679982491,"version":"4.1.0"},"reference-count":92,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Biosci."],"abstract":"<jats:p>Liquid-liquid phase separation (LLPS) coordinates biomolecular condensates to establish three-dimensional chromatin architecture and epigenetic regulation. The progressive loss of epigenetic information is a fundamental, reversible driver of cellular senescence. In this review, we systematically synthesize emerging evidence on the spatiotemporal dynamics of LLPS-mediated chromatin compartmentalization during the aging process. We highlight how age-dependent alterations in histone, RNA, and DNA modifications disrupt multivalent interactions, leading to constitutive heterochromatin dissolution, aberrant transcriptional condensate formation, and nucleolar expansion. Furthermore, biomolecular condensates undergo age-dependent biophysical maturation\u2014shifting from dynamic liquid states to solid-like aggregates\u2014which dictates structural chromatin erosion and topologically associating domain (TAD) fusion. These diverse biophysical defects can be consolidated within a unified \u201ccondensatopathy\u201d framework, encompassing both loss-of-function failures and toxic gain-of-function protein aggregations across somatic aging, stem cell exhaustion, and neurodegeneration. Understanding how phase separation regulates higher-order chromatin structures provides profound insights into aging trajectories. Ultimately, selectively modulating the material properties of biomolecular condensates, rather than merely dissolving them, offers a transformative precision therapeutic paradigm to restore epigenetic fidelity and counteract age-related diseases.<\/jats:p>","DOI":"10.3389\/fmolb.2026.1896884","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T10:50:14Z","timestamp":1790679014000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["High-order chromatin structures mediated by phase separation in cell senescence"],"prefix":"10.3389","volume":"13","author":[{"given":"Wenjing","family":"Sun","sequence":"first","affiliation":[{"name":"Technology Center of Shanghai Tobacco Group Co., Ltd.","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boxian","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Pesticide and Chemical Biology of Ministry of Education, Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaoyong","family":"Xu","sequence":"additional","affiliation":[{"name":"Technology Center of Shanghai Tobacco Group Co., Ltd.","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Wang","sequence":"additional","affiliation":[{"name":"Technology Center of Shanghai Tobacco Group Co., Ltd.","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Cao","sequence":"additional","affiliation":[{"name":"Technology Center of Shanghai Tobacco Group Co., Ltd.","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangzhong","family":"Wang","sequence":"additional","affiliation":[{"name":"Technology Center of Shanghai Tobacco Group Co., Ltd.","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiale","family":"Wang","sequence":"additional","affiliation":[{"name":"Technology Center of Shanghai Tobacco Group Co., Ltd.","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenbo","family":"Gu","sequence":"additional","affiliation":[{"name":"Technology Center of Shanghai Tobacco Group Co., Ltd.","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengjun","family":"Xu","sequence":"additional","affiliation":[{"name":"Tobacco Research Institute, The Chinese Academy of Agricultural Sciences","place":["Qingdao, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Pesticide and Chemical Biology of Ministry of Education, Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenyan","family":"Xie","sequence":"additional","affiliation":[{"name":"Technology Center of Shanghai Tobacco Group Co., Ltd.","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"4990","DOI":"10.1038\/s41467-019-13018-3","article-title":"Inhibition of DNA damage response at telomeres improves the detrimental phenotypes of hutchinson-gilford progeria syndrome","volume":"10","author":"Aguado","year":"2019","journal-title":"Nat. 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