| Autor: |
Signal B; Menzies Institute for Medical Research, University of Tasmania, 17 Liverpool Street, Hobart, TAS 7000, Australia., Phipps AJ; Wicking Dementia Research and Education Centre, College of Health and Medicine, University of Tasmania, 17 Liverpool Street, Hobart, TAS 7000, Australia., Giles KA; Menzies Institute for Medical Research, University of Tasmania, 17 Liverpool Street, Hobart, TAS 7000, Australia.; Children's Medical Research Institute, University of Sydney, 214 Hawkesbury Road, Westmead, NSW 2145, Australia., Huskins SN; Menzies Institute for Medical Research, University of Tasmania, 17 Liverpool Street, Hobart, TAS 7000, Australia., Mercer TR; Australian Institute for Bioengineering and Nanotechnology, Corner College and Cooper Roads, Brisbane, QLD 4072, Australia., Robinson MD; SIB Swiss Institute of Bioinformatics, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland., Woodhouse A; Wicking Dementia Research and Education Centre, College of Health and Medicine, University of Tasmania, 17 Liverpool Street, Hobart, TAS 7000, Australia., Taberlay PC; Menzies Institute for Medical Research, University of Tasmania, 17 Liverpool Street, Hobart, TAS 7000, Australia. |
| Abstrakt: |
Neurons are central to lifelong learning and memory, but ageing disrupts their morphology and function, leading to cognitive decline. Although epigenetic mechanisms are known to play crucial roles in learning and memory, neuron-specific genome-wide epigenetic maps into old age remain scarce, often being limited to whole-brain homogenates and confounded by glial cells. Here, we mapped H3K4me3, H3K27ac, and H3K27me3 in mouse neurons across their lifespan. This revealed stable H3K4me3 and global losses of H3K27ac and H3K27me3 into old age. We observed patterns of synaptic function gene deactivation, regulated through the loss of the active mark H3K27ac, but not H3K4me3. Alongside this, embryonic development loci lost repressive H3K27me3 in old age. This suggests a loss of a highly refined neuronal cellular identity linked to global chromatin reconfiguration. Collectively, these findings indicate a key role for epigenetic regulation in neurons that is inextricably linked with ageing. |
