ReviewFrontiers in molecular biosciences2026
High-order chromatin structures mediated by phase separation in cell senescence.
Review in Frontiers in molecular biosciences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
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-shifting from dynamic liquid states to solid-like aggregates-which dictates structural chromatin erosion and topologically associating domain (TAD) fusion. These diverse biophysical defects can be consolidated within a unified "condensatopathy" 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.
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