Meta-analysis of gene expression reversals in ageing brain

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Tezin Türü: Yüksek Lisans

Tezin Yürütüldüğü Kurum: Orta Doğu Teknik Üniversitesi, Fen Edebiyat Fakültesi, Biyolojik Bilimler Bölümü, Türkiye

Tezin Onay Tarihi: 2016

Öğrenci: HANDAN MELİKE DÖNERTAŞ

Danışman: MEHMET SOMEL

Özet:

Brain ageing is characterised by disruptive changes in cognitive abilities, histology, and anatomy. The underlying molecular nature of brain ageing, on the other hand, is little understood, partly due to the stochastic and heterogeneous nature of ageing process. In this study, using published microarray studies spanning 22 brain regions with 1,015 samples, gene expression changes in ageing are analysed in comparison to those in postnatal development. A previous observation that mRNA abundance of a large number of genes in the ageing prefrontal cortex reverses toward pre-adolescent levels, is shown to be a widespread phenomenon across different brain regions. Furthermore, functional analysis reveals that gene expression reversals are consistently associated with decline in neuronal / synaptic gene expression across all studied brain regions, and thus may be linked to ageing-related phenotypes such as decline in cognitive functions. Regulatory analysis show that the genes increasing in expression in development and decreasing in expression in ageing are associated with several trans-regulators, whereas there is no consistent association with any potential trans-regulator for the genes decreasing in expression in development and increasing in expression in ageing. Overall, the results show that meta-analysis is crucial for ageing studies due to the stochastic nature of ageing and that studying gene expression change in ageing in the context of changes in development is a promising approach to discover the molecular mechanisms of ageing.