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

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 w...

Full description

Saved in:
Bibliographic Details
Published in:Scientific reports 2017-07, Vol.7 (1), p.5894-13, Article 5894
Main Authors: Dönertaş, Handan Melike, İzgi, Hamit, Kamacıoğlu, Altuğ, He, Zhisong, Khaitovich, Philipp, Somel, Mehmet
Format: Article
Language:English
Subjects:
45/61
45/91
631/114
631/208/199
631/337/2019
631/378/2611
Aging
Aging - genetics
Alzheimer Disease - genetics
Brain
Brain - cytology
Cell Differentiation - genetics
Datasets
Gene expression
Gene Expression Regulation, Developmental
Gene Ontology
Humanities and Social Sciences
Humans
multidisciplinary
Neurons - cytology
Oligonucleotide Array Sequence Analysis
Prefrontal cortex
Science
Science (multidisciplinary)
Stochasticity
Structure-function relationships
Synapses - metabolism
Up-Regulation - genetics
Young Adult
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-017-05927-4