Inhibition of histone lysine demethylase restores learning and memory in aged mice.

ABSTRACT: Chromatin undergoes dramatic changes during the ageing process. In the brain, these chromatin changes are thought to underlie age-associated deficits in the activity-dependent gene transcription necessary for memory consolidation. Here, we show that the levels of a specific histone post-translational modification (PTM), trimethylation of lysine 4 on histone 3 (H3K4me3) is markedly increased in the hippocampus of aged mice and that the activity-induced increase in H3K4me3 that is observed in response to a learning stimulus in young mice, is severely blunted in the aged hippocampus. H3K4me3 typically marks open, accessible chromatin at the transcriptional start sites (TSSs) of actively transcribed genes. We identify altered H3K4me3 peaks at TSSs and show that ca. 90% of the activity-induced

SUBMITTER: Bhatt SU 

PROVIDER: S-EPMC12767655 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature