ArticleResearch square2025
Age-associated G-quadruplex accumulation and DDX5 loss shape chromatin landscapes in human astrocytes.
Article in Research square, 2025. 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
Aging disrupts genome organization and transcriptional fidelity, but the role of non-canonical DNA structures in the aging process remains unclear. G-quadruplexes (G4s), stable guanine-rich DNA and RNA structures are established regulators of gene expression and genome integrity, yet their contribution to physiological aging is unknown. Using fluorescent imaging with primary human astrocytes derived from individuals spanning early to late adulthood (22-73 years) reveals an accumulation of G4s and a reduced nuclear expression of the G4-resolving helicase DDX5 in aging cells. To investigate how these changes relate to genome architecture, we performed ATAC-seq to profile chromatin accessibility and G4 CUT&Tag to profile the G4 landscape across all astrocyte cultures. Older cells exhibited global chromatin compaction and focal G4 enrichment, with gains occurring in both accessible and closed chromatin regions, indicating
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