Investigation of Transcriptome Dysregulation in Brain Ageing

Human brain ageing is characterised by decreasing cognitive function of various severity affecting 60% of aged population. Decline in cognitive capabilities might be the only symptom of ageing in otherwise healthy humans. Even more important is ageing-related development of neurodegenerative diseases, which present a significant burden to society and the health care system. Diminished cognitive function with increased age is likely a manifestation of dysregulated synaptic function and ineffective neurotransmission. We recently reported a comparative analysis of the synaptosome transcriptome in ageing mouse brain. Our results revealed changes in expression of genes contributing to biological pathways related to neurite guidance and synaptosomal physiology (Fig. 2) as well as perturbation of long non-coding RNAs (lncRNAs). The aim of this project is to explore mechanisms which lead to reshaping of the non-coding transcriptome as a result of brain ageing. The project will employ meta-analytical and experimental approaches to investigate novel lncRNAs involved in ageing-related changes of gene expression.

Enrichment map visualising gene ontology terms enriched in protein-
coding genes which are differentially expressed in ageing synaptosome

(Chen et al. 2017).

References

  • Chen BJ, Ueberham U, Mills JD, Kirazov L, Kirazov E, Knobloch M, Bochmann J, Jendrek R, Takenaka K, Bliim N, Arendt T & Janitz M, 2017, ‘RNA sequencing reveals pronounced changes in the noncoding transcriptome of aging synaptosomes’, Neurobiol Aging, 56:67-77.
  • Chen BJ, Mills JD, Takenaka K, Bliim N, Halliday GM & Janitz M, 2016, ‘Characterization of circular RNAs landscape in multiple system atrophy brain’, J Neurochem, 139:485-496.
  • Huang S, Yang B, Chen BJ, Bliim N, Ueberham U, Arendt T & Janitz M, 2017, ‘The emerging role of circular RNAs in transcriptome regulation’, Genomics, pii: S0888-7543(17)30046-0

BABS academic responsible for this project:

Currently Active: 
Yes