Gene expression reversal toward pre-adult levels in the aging human brain and age-related loss of cellular identity


Donertas H. M. , İZGİ H. , Kamacioglu A., He Z., Khaitovich P., SOMEL M.

SCIENTIFIC REPORTS, cilt.7, 2017 (SCI İndekslerine Giren Dergi) identifier identifier identifier

Özet

It was previously reported that mRNA expression levels in the prefrontal cortex at old age start to resemble pre-adult levels. Such expression reversals could imply loss of cellular identity in the aging brain, and provide a link between aging-related molecular changes and functional decline. Here we analyzed 19 brain transcriptome age-series datasets, comprising 17 diverse brain regions, to investigate the ubiquity and functional properties of expression reversal in the human brain. Across all 19 datasets, 25 genes were consistently up-regulated during postnatal development and down-regulated in aging, displaying an "up-down" pattern that was significant as determined by random permutations. In addition, 113 biological processes, including neuronal and synaptic functions, were consistently associated with genes showing an up-down tendency among all datasets. Genes up-regulated during in vitro neuronal differentiation also displayed a tendency for up-down reversal, although at levels comparable to other genes. We argue that reversals may not represent aging-related neuronal loss. Instead, expression reversals may be associated with aging-related accumulation of stochastic effects that lead to loss of functional and structural identity in neurons.