Multiscale chromatin remodeling during cellular senescence. (IMAGE)
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Chromatin loops, which are formed by CTCF and cohesin, mediate precise long-range gene regulation by connecting enhancers with their target promoters. During aging and cellular senescence, these loops undergo widespread collapse and reorganization, resulting in the destabilization of transcriptional programs. During cellular senescence, cohesin, a key factor mediating chromatin loop formation, undergoes redistribution, resulting in rewiring of enhancer–promoter interactions. In contrast, during cellular aging, altered activity of transcription factors such as YY1 and AP-1 contributes to progressive disruption of super-enhancer-associated chromatin loops and age-associated transcriptional reprogramming. Notably, loop dynamics are intricately linked to higher-order chromatin architecture. These structural alterations not only reflect but also actively contribute to age-related transcriptional dysregulation and the onset of aging-associated diseases. In summary, the remodeling of chromatin loops represents a central mechanism underlying 3D genomic dysfunction in aging, functionally connecting transcriptional imbalance with cellular senescence and pathology, thereby highlighting its potential as a target for therapeutic strategies. Collectively, these studies indicate that although cellular senescence and organismal aging share convergent features of 3D genome remodeling, including compartment blurring, TAD destabilization, and loop reprogramming, the underlying drivers and structural outcomes are highly context-dependent, varying across senescence modalities and aging tissues.
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Aging Research, Tsinghua University Press
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