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

Abstract 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 declin...

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Autores principales:	Handan Melike Dönertaş, Hamit İzgi, Altuğ Kamacıoğlu, Zhisong He, Philipp Khaitovich, Mehmet Somel
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ededa3881d4b43a9b6f96ce5433f351a
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spelling	oai:doaj.org-article:ededa3881d4b43a9b6f96ce5433f351a2021-12-02T16:06:50ZGene expression reversal toward pre-adult levels in the aging human brain and age-related loss of cellular identity10.1038/s41598-017-05927-42045-2322https://doaj.org/article/ededa3881d4b43a9b6f96ce5433f351a2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05927-4https://doaj.org/toc/2045-2322Abstract 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.Handan Melike DönertaşHamit İzgiAltuğ KamacıoğluZhisong HePhilipp KhaitovichMehmet SomelNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Handan Melike Dönertaş Hamit İzgi Altuğ Kamacıoğlu Zhisong He Philipp Khaitovich Mehmet Somel Gene expression reversal toward pre-adult levels in the aging human brain and age-related loss of cellular identity
description	Abstract 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.
format	article
author	Handan Melike Dönertaş Hamit İzgi Altuğ Kamacıoğlu Zhisong He Philipp Khaitovich Mehmet Somel
author_facet	Handan Melike Dönertaş Hamit İzgi Altuğ Kamacıoğlu Zhisong He Philipp Khaitovich Mehmet Somel
author_sort	Handan Melike Dönertaş
title	Gene expression reversal toward pre-adult levels in the aging human brain and age-related loss of cellular identity
title_short	Gene expression reversal toward pre-adult levels in the aging human brain and age-related loss of cellular identity
title_full	Gene expression reversal toward pre-adult levels in the aging human brain and age-related loss of cellular identity
title_fullStr	Gene expression reversal toward pre-adult levels in the aging human brain and age-related loss of cellular identity
title_full_unstemmed	Gene expression reversal toward pre-adult levels in the aging human brain and age-related loss of cellular identity
title_sort	gene expression reversal toward pre-adult levels in the aging human brain and age-related loss of cellular identity
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/ededa3881d4b43a9b6f96ce5433f351a
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Gene expression reversal toward pre-adult levels in the aging human brain and age-related loss of cellular identity

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