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Recapitulation of juvenile-like histone landscape in aged neurons

Citation

Phipps, A and Giles, K and Mercer, T and Vickers, JC and Robinson, M and Taberlay, PC and Woodhouse, A, Recapitulation of juvenile-like histone landscape in aged neurons, Australian Dementia Forum 2019, 13-14 June 2019, Hobart, Tasmania (2019) [Conference Extract]

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Abstract

The greatest risk factor for dementia is increasing age. During healthy aging the activity of neurons underlie a range of cognitive trajectories from unimpaired to significant decline. The epigenome is the interface between our genes and the environment and comprises a highly interactive network of chemical moieties (including histone modifications). The epigenetic signature of each cell type is unique, yet few studies have examined the epigenome in aged neurons. We characterised H3K27ac and H3K4me3 histone modifications using ChIP-seq in forebrain neurons from 3, 6, 12, and 24 month (m) old C57/Bl6 mice (n=5/timepoint). H3K27ac and H3K4me3 marking was enriched at promoters and enhancers in neurons from juvenile (3m) and aged (24m) mice compared to neurons from adult mice (6m&12m). Gene ontology (GO) analysis annotated to synaptic and core molecular processes across life. Developmental GOs were unique to juvenile neurons, while annotations that were unique to adult neurons included axonal transport, protein folding and membrane depolarisation. GO pathways that were unique to aged neurons included apoptosis, autophagy and RNA processing. Surprisingly, we detected a partial recapitulation of a juvenile-like histone landscape in aged neurons; >25% of H3K27ac and H3K4me3 differentially marked sites were shared between juvenile and aged neurons and >87% of these shared sites were consistently enriched in both juvenile and aged neurons. This work reveals epigenetic alterations that impact neurons across aging. Our long-term goal is to identify the epigenetic changes that drive neuronal dynamics in healthy aging and dysfunction in dementia to discover direct and indirect therapeutic targets.

Item Details

Item Type:Conference Extract
Keywords:neurons, aging, histone modifications, H3K4me3, H3K27ac
Research Division:Biomedical and Clinical Sciences
Research Group:Neurosciences
Research Field:Neurology and neuromuscular diseases
Objective Division:Expanding Knowledge
Objective Group:Expanding knowledge
Objective Field:Expanding knowledge in the biomedical and clinical sciences
UTAS Author:Phipps, A (Dr Andrew Phipps)
UTAS Author:Vickers, JC (Professor James Vickers)
UTAS Author:Taberlay, PC (Associate Professor Phillippa Taberlay)
UTAS Author:Woodhouse, A (Dr Adele Woodhouse)
ID Code:144038
Year Published:2019
Deposited By:Wicking Dementia Research and Education Centre
Deposited On:2021-04-15
Last Modified:2021-04-20
Downloads:0

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