Evidence suggests that epigenetic mechanisms contribute to the aging process and the development of aging-associated diseases. Notably, several studies have identified epigenetic and chromatin changes in hippocampal neurons during aging, impacting gene expression patterns. However, the effects of aging on the neuronal 3D chromatin organization are unknown. In a new study, Gancedo-Verdejo and colleagues analyzed the changes in the 3D chromatin organization of mouse hippocampal neurons during aging, utilizing the low-input promoter capture Hi-C (liCHi-C) technique. They found that young and old mouse hippocampi displayed several differences in chromatin interactions, notably a reduction of interactions with bivalent promoters in older tissues. The team also performed an RNA sequencing analysis of young and old mouse dorsal hippocampi, allowing them to link the age-associated changes in chromatin organization and gene expression. In addition, the team investigated the effects of environmental enrichment (EE) on the mouse brain 3D chromatin structure, revealing an age-dependent impact of EE. Notably, while EE promoted aging-like changes in young mice, potentially related to brain maturation, the intervention prevented the alterations in chromatin structures observed in old mice, suggesting neuronal rejuvenation.
Original reference: Gancedo-Verdejo, J. et al. Cell Rep. 44, 116182 (2025)
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